Rssdi 2022 T2DM

International Journal of Diabetes in Developing Countries (October 2022) 42 (Suppl 1):S1–S143
https://doi.org/10.1007/s13410-022-01129-5
GUIDELINES
RSSDI Clinical Practice Recommendations for the Management

of Type 2 Diabetes Mellitus 2022
Brij Mohan Makkar, Ch.Vasanth Kumar, Banshi Saboo, Sanjay Agarwal

On behalf of RSSDI 2022 Consensus Group
Clinical Practice Recommendations Review Committee
A Ramachandran, Anoop Misra, Banshi Saboo, Brij Mohan Makkar, Ch.

Vasanth Kumar, Krishna Seshadri, Nikhil Tandon, Rajeev Chawla, S V
Madhu, Sanjay Agarwal, Shashank Joshi, Sidhartha Das, V Mohan
RSSDI Consensus Groups
Members: Dr RK Goenka, Dr
Diagnosis and Classification of Coordinators: Dr SV Madhu, Dr
Sandeep Desai, Dr Ashish
Diabetes RM Anjana
Dengra
Members: Dr Siddharth Das, Dr
Nihal Thomas, Dr Alok Hypoglycaemia Coordinators: Dr Anand Moses, Dr
Kanungo L Sreenivasamurthy
Members: Dr Dheeraj Kapoor, Dr
Prevention (Including Screening Coordinator: Dr Ambady
Shunmugavelu, Dr Shachin K.
and Early Detection) and Ramachandran, Dr Anil
Gupta
Remission Bhansali
Members: Dr CS Yajnik, Dr Chronic complications 1: Coordinators: Dr Rajeev Chawla,
Sambit Das, Dr Paraminder Retinopathy, Neuropathy, Dr Rakesh Sahay
Singh Diabetic Kidney Disease Members: Dr SK Mahapatro, Dr
Vipin Mehra, Dr Sadasiva Rao
Medical Nutrition Therapy and Coordinators: Dr Naval K.Vikram,
Lifestyle Modification Dr Narsingh Verma, Chronic Complications 2: Stroke, Coordinators: Dr Vijay
Members: Dr Anjali Nakra, Dr PAD, Diabetic Foot Vishwanathan, Dr Ashu Rastogi
Anubha Srivastava, Dr Sanjib Members: Dr Ghanshyam Goyal,
Medhi, Dr Chandni R Dr Johnny Kannampali, Dr
Avijit Royzada
Treatment 1: Oral Hypoglycemic Coordinators: Dr V Panikar, Dr.
Agents Bikash Bhattacharjee Diabetes and Heart Coordinators: Dr Shailaja Kale, Dr
Members: Dr Prakash Keswani, Dr Arvind Gupta
Pravin K Kalvit, Dr Members: Dr Digambar Naik, Dr
Sureshkumar Pichakacheri Ripun Borpuzari, Dr Ashish K.
Saxena
Treatment 2: Injectables Coordinators: Dr AK Das, Dr
Sanjay Reddy Other Complications- Bone, Skin Coordinators: Dr Ambrish Mithal,
Members: Dr SK Wangnoo, Dr And Hepatomegaly Dr Sanjay Bhadada
Ajay Kumar, Dr Sunil Jain, Dr Members: Dr Ravi Kant, Dr
Tejas Kamat Abhishek Shrivastva
Individualizing Therapy and Coordinators: Dr V Mohan, Dr SR Obesity and Type 2 Diabetes Coordinators: Dr Anoop Misra, Dr
Precision Diabetology Aravind Mellitus Neeta Deshpande
Members: Dr Sanjeev Phatak, Dr Members: Dr Nitin Kapoor, Dr
Jajseet Wasir, Dr Krishna Rucha Mehta, Dr Soumitra
Prasanthi Ghosh
Postprandial Hyperglycaemia Coordinators: Dr Shashank Joshi, Vaccinations In People With Coordinators: Dr Shubhankar
Dr Kaushik Pandit Diabetes Chowdhary, Dr JK Sharma
Members: Dr SK Sharma, Dr Members: Dr Mangesh Tiwaskar,
Vinay Dhandhania, Dr Rupam Dr Agam Vora, Dr Jayant Panda,
Das, Dr V.K Bhardwaj Dr Meena Chhabra
Acute Metabolic Complications Coordinators: Dr Sanjay Agarwal, Sexual Dysfunction Coordinators: Dr Samar Banerjee,
Dr Kamlakar Tripathi Dr Mithun Bhartiya
S2 International Journal of Diabetes in Developing Countries (October 2022) 42 (Suppl 1):S1–S143
Members: Dr Urman Dhruv, Dr Psychosocial Issues Coordinators: Dr Sanjay Kalra, Dr

Deepak Jumani, Dr Bharti Kalra Rishi Shukla
Clinical Monitoring Coordinators: Dr AG Members: Dr GR Sridhar, Dr
Unnikrishnan, Dr Rajiv Kovil Saurabh Srivastava, Dr BK
Members: Dr Anjali Bhatt, Dr Singh, Dr Sanjay Singh
Nanditha Arun, Dr Supratik Type 2 Diabetes Mellitus in Coordinators: Dr Nikhil Tandon,
Bhattacharya Young and Adolescents Dr Ranjit Unnikrishnan
Technologies Coordinators: Dr Jothydev Members: Dr Minal Mohit, Dr
Kesavadev, Dr Manoj Chawla Arvinda J, Dr Ajoy Tewari, Dr
Members: Dr Rakesh Parikh, Dr JP Naval Chandra
Sai, Dr Amit Gupta Diabetes and Pregnancy – Pre Coordinators: Dr Sunil Gupta, Dr
Special Situations Coordinators: Dr Sujoy Ghosh, Dr GDM & GDM Usha Sriram
G Vijaykumar Members: Dr Shalini Jaggi, Dr
Members: Dr Rajesh Rajput, Dr Debmalya Sanyal, Dr Mythili
NK Singh, Dr MK Garg, Dr Ayyagari, Dr K. Shankar
Muralidharan C Type 2 Diabetes Mellitus and Coordinators: Dr Anuj
Fasting and Diabetes Coordinators: Dr Sarita Bajaj, Dr Hypertension Maheshwari, Dr Alok Sachan
Pratap Jhetwani Members: Dr Vipin Talwar, Dr
Members: Dr Hemant Thacker, Dr Ravi Shankar Erukulapati, Dr
G Vijay Kumar, Dr Jimit Sujeet Raina, Dr K Vijay Kumar
Vadgama, Dr D Selvaraj Diabetes in Elderly Coordinators: Vinod Kumar and O
Education Coordinators: Dr Ch Vasanth P Sharma
Kumar, Dr Purvi Chawla Members: DC Thirupathi Rao,
Members: Dr GD Ramchandani, Yousuf Khan, Subhash Kumar,
Dr KN Manohar, Dr P.D Pahwa, and Manisha Taneja
Dr Suman R
DIAGNOSIS AND CLASSIFICATION OF DIABETES The diagnosis of diabetes in pregnancy is dealt with in the Chapter on
Hyperglycaemia in Pregnancy.
Recommendations
NOTE:
Recommended Care • Estimation of HbA1c should be performed using NGSP standardized
method.
Prediabetes/ intermediate hyperglycemia can be diagnosed with any of the following • Venous plasma is used for the estimation of glucose
criteria:
• Plasma must be separated soon after collection because the blood glu-
• Impaired fasting glucose (IFG): FPG 110 mg/dL to 125 mg/dL or
• Impaired glucose tolerance (IGT): 2-h plasma glucose (2-h PG) during 75-g OGTT cose levels drop by 5%–8% hourly if whole blood is stored at room
140 mg/dL to 199 mg/dL or temperature.
• HbA1c ≥5.7%-6.4% • Capillary glucose estimation methods are not routinely recommended
Diabetes can be diagnosed with any of the following criteria:
for diagnosis of diabetes/prediabetes/ intermediate hyperglycemia in the
• FPG ≥126 mg/dL* or
• FPG ≥126 mg/dL and/or 2-h PG ≥200 mg/dL using 75-g OGTT clinic setting; however, they may be used in epidemiological settings for
• HbA1c≥6.5% ** or assessing the population prevalence of diabetes and for individual diag-
• Random plasma glucose ≥200 mg/dL in the presence of classic diabetes symptoms nosis in resource-constrained environments where facilities for venous
Asymptomatic individuals with a single abnormal test should have the test repeated to plasma glucose estimation are not immediately available. However,
confirm the diagnosis unless the result is unequivocally abnormal.
Individuals diagnosed with diabetes should be classified according to the World Health individuals detected to have dysglycemia using capillary blood glucose
Organisation classification system. should have their diagnosis confirmed at the earliest by one of the
methods mentioned above.1
For more details on glucose estimation, refer 2

Limited Care
*FPG is defined as glucose estimated after no caloric intake for at least 8–
Diabetes can be diagnosed with any of the following criteria:
• FPG ≥126 mg/dL* or
12 hours.
• FPG ≥126 mg/dL and/or 2-h plasma glucose ≥200 mg/dL using 75-g OGTT or **Using a method that is National Glycohemoglobin Standardization
• Random plasma glucose ≥200 mg/dL in the presence of classic diabetes symptoms Program (NGSP) certified. For more on HbA1c and NGSP, please visit
Asymptomatic individuals with a single abnormal test should have the test repeated to http://www.ngsp.org.
confirm the diagnosis unless the result is unequivocally abnormal
International Journal of Diabetes in Developing Countries (October 2022) 42 (Suppl 1):S1–S143 S3
Background - HbA1c ≥6.5% as an optimal level for diagnosis of diabetes in Indian

The diagnostic criteria of diabetes have constantly been evolving. Both type 1 patients
and type 2 diabetes mellitus are diagnosed based on the plasma glucose - HbA1c cannot be used as the ‘sole’ measurement for the diagnosis of
criteria, either the fasting plasma glucose (FPG) levels or the 2-h plasma diabetes in Indian settings.
post-load glucose (2-h PG) levels during a 75-g oral glucose tolerance test - However, the panel emphasized that HbA1c can be used in settings
(OGTT), or the glycosylated hemoglobin (HbA1c) criteria which reflect the where an appropriate standardized method is available.
average plasma glucose concentration over the previous 8–12 weeks.3 The
International Expert Committee Report recommends a cut-point of ≥6.5% for These recommendations are based on the following evidence:
HbA1c for diagnosing diabetes as an alternative to fasting plasma glucose • A recent study conducted on Singapore residents of Chinese, Malay,
(FPG≥7.0 mmol/L).4HbA1c testing has some substantial advantages over and Indian races to assess the performance of HbA1c as a screening test
FPG and OGTT, such as convenience, pre-analytical stability, and fewer in Asian populations suggested that HbA1c is an appropriate alternative
day-to-day fluctuations due to stress and illness. 4 Additionally, HbA1c has to FPG as a first-step screening test. A combination of HbA1c with a
been recognized as a marker to assess secondary vascular complications due cut-off of ≥6.1% and FPG level ≥100 mg/dL would improve detection
to metabolic derailments in susceptible individuals.3,5,6However, given ethnic in patients with diabetes.7
differences in sensitivity and specificity of HbA1c, population-specific cut- • A study to assess the diagnostic accuracy and optimal HbA1c cut-offs
offs might be necessary.7,8The high prevalence of iron deficiency anemia and for diabetes and prediabetes/ intermediate hyperglycemia among high-
(in specific geographies) hemoglobinopathies, and thalassemia in India may risk south Indians suggested that HbA1c ≥6.5% can be defined as a cut-
lead to over- or underdiagnosis of diabetes/prediabetes/ intermediate hyper- off for diabetes and that HbA1c ≥5.9% is optimal for prediabetes/ inter-
glycemia when HbA1c is used as the sole diagnostic criterion.9,10Moreover, mediate hyperglycemia diagnosis and that a value <5.6% excludes
measuring HbA1c is expensive compared to FPG assessments. prediabetes/ intermediate hyperglycemia/diabetes status.11
Standardization of measurement techniques and laboratories is poorly prac- • Data from a community-based randomized cross-sectional study in ur-
ticed across India.11 Also, in several countries, including India, HbA1c dem- ban Chandigarh suggest that the HbA1c cut point of 6.5% has optimal
onstrated inadequate predictive accuracy in the diagnosis of diabetes; there is specificity of 88%. In comparison, the cut-off end of 7.0% has a sensi-
no consensus on an appropriate cut-off point of HbA1c for the diagnosis of tivity of 92% for the diagnosis of diabetes.13
diabetes in this high-risk population.12 In view of this, the panel expressed • The results of the Chennai Urban Rural Epidemiology Study (CURES)
concerns about using HbA1c as the sole criterion for the diagnosis of diabe- demonstrated 88.0% sensitivity and 87.9% specificity for the detection of
tes, particularly in resource-constrained settings. Therefore, a combination of diabetes when the HbA1c cut-off point is 6.1% (based on 2-h post-load
HbA1cand FPG would improve the identification of individuals with diabe- plasma glucose) and 93.3% sensitivity and 92.3% specificity when HbA1c
tes mellitus and prediabetes/ intermediate hyperglycemia in limited resource cut off point is 6.4% (when diabetes was defined as FPG ≥7.0 mmol/l).14
settings like India.
Classification of Diabetes
Considerations
The decision to set diagnostic threshold values was based on the cost- The World Health Organisation15 in 2019, revised the classification of
effective strategies for diagnosing diabetes that was reviewed in the diabetes to provide the best possible compromise between an etiological
Indian context. and clinical classification and to develop a classification system that is
feasible to implement in different settings throughout the globe. This
Rationale And Evidence system divides diabetes into six broad subgroups (Table 1).
Glycosylated hemoglobin cut off for diagnosis of diabetes in Indian patients
• The RSSDI expert panel suggests Table 1: Six groups of Diabetes according to the WHO
S. No Category antidiabetic agents and present more with peripheral neuropathy, infec-
1. Type 1 diabetes (T1DM) tions, and microvascular complications, while the macrovascular disease
2. Type 2 diabetes (T2DM) is rare. Lean T2DM is characterized by body mass index (BMI) below 19,
Hybrid forms of diabetes: no evidence of malnutrition, pancreatic autoimmune β cell or exocrine
3.
- Slowly evolving immune-mediated diabetes in adults (previously termed pancreatic disease, and good C-peptide levels17 . Recently, another phe-
LADA-latent autoimmune diabetes of adults) notype of lean diabetes has been described, characterized by low c-pep-
- Ketosis-prone T2DM (previously termed Flatbush diabetes)
tide, lower hepatic glucose output by deuterated glucose measurements,
Other specific types
- Monogenic diabetes (defects of beta-cell function or insulin action)
and total body fat lower than in T2DM18. More studies are needed to
- Diseases of the exocrine pancreas evaluate the pathophysiology of diabetes in these lean individuals.
- Endocrinopathies T2DM encompasses a broad spectrum of varying insulin deficiency and
4.
- Drug- or chemical-induced diabetes resistance combinations. Recently,21, it has been suggested that there are
- Infection-related diabetes
- Uncommon forms of immune-mediated diabetes different subtypes of T2DM based on the “clustering” of several pheno-
- Other genetic syndromes sometimes associated with diabetes typic variables. Attempts20 to identify similar subtypes of T2DM in the
Unclassified diabetes Indian population have led to the identification of four “clusters,” two of
5. - A temporary category used when diabetes does not fit into any of the other
categories
which are identical to those identified in the Caucasian population and
Hyperglycemia first detected during pregnancy
two of which are unique to India. These clusters are:
- Diabetes mellitus in pregnancy
6.
- Gestational diabetes mellitus Hyperglycaemia first detected during • Severe insulin-deficient diabetes (SIDD) (characterized by low BMI and
pregnancy waist circumference, poor C-peptide, and high HbA1c)
• Insulin-resistant obese diabetes (IROD) (Novel cluster) (High BMI and waist
Another phenotype of diabetes, observed in 4 to 11% of T2DM in the circumference, preserved C-peptide, and moderately elevated HbA1c)
Indian context, is lean type 2 diabetes16. They have inherent peculiarities • Combined insulin resistant and deficient diabetes (CIRDD) (Novel
in hepatic insulin metabolism and altered behavior of key enzymes in- cluster) (Low or normal BMI and waist circumference, preserved C-
volved in carbohydrate metabolism. They respond well to oral peptide, high HbA1c and triglycerides)
• Mild age-related diabetes (MARD) (Older age at onset, good C-peptide, • Other pharmacological interventions with pioglitazone, orlistat, vitamin D, or bariatric
surgery are not recommended.
good HDL, lower HbA1c)
• People with prediabetes should be educated on:
- Weight management through optimal diet and physical activity
There is some evidence to suggest that these “clusters” differ in the natural
21
- Stress management
history of the disease, risk of complications, and response to treatment. - Avoidance of alcohol and tobacco
Implementation Remission
Definition: Remission should be defined as a return of HbA1c to <6.5% that occurs spontaneously or
Individuals should be educated on the advantages of early diagnosis and
following an intervention and persists for at least three months without usual glucose-lowering
encouraged to participate in community screening programs for diagnosis. pharmacotherapy.
• The patient's remission of diabetes can be documented if this is not due to complications,
PREVENTION (INCLUDING SCREENING AND EARLY comorbid conditions, or concomitant therapy.
DETECTION) AND REMISSION • In a setting where HbA1c is an unreliable marker of chronic glycemic control, FPG or CGM
values can be used for diagnosis. A FPG <126 mg/dL (<7.0 mmol/L) or eA1C <6.5%
Recommendations calculated from CGM values can be used as alternate criteria.
• Testing of HbA1c to document a remission should be performed just before intervention and
Recommended Care at least three months after initiation of the intervention and withdrawal of any glucose-
lowering pharmacotherapy.
Screening and early detection
• In the case of continued use of glucose-lowering drugs for other non-glycemic indications,
• The healthcare service provider should develop a program to identify people with
diabetes remission cannot be defined.
undiagnosed diabetes.
• The program should be based on the available support from the healthcare system/service • Testing to determine long-term remission maintenance should be done yearly or more
capable of effectively treating newly detected cases of diabetes. frequently if indicated.
• Opportunistic screening for undiagnosed diabetes and prediabetes is recommended. It should
include: • Testing for potential complications of diabetes should be continued as routinely
- Individuals presenting to healthcare settings for an unrelated illness recommended for a person with diabetes.
- Family members of patients with diabetes • Remission of diabetes should be defined in the context of type-2 diabetes only.
- Antenatal care
- Dental care Surgical Remission
• Bariatric surgery remains one of the best options for the remission of diabetes.
- Overweight children and adolescents at the onset of puberty
• Bariatric surgery produces significantly more consistent long-term remission than lifestyle
• Wherever feasible, community screening may be done modifications and diet.
• Detection programs are usually based on a two-step approach: • Quantum weight loss correlates with long-term remission.
- Step 1: Identify high-risk individuals using a non-invasive risk assessment • RYG is the gold standard surgical procedure.
• Complications rates of surgery are meager, and long-term vitamin supplementation is required
questionnaire
- Step 2: Glycemic measure in high-risk individuals here random capillary glucose
between 140mg/dL and 200 mg/dL is detected, and OGTT should be performed.
Limited Care
• Universal screening and diagnosis of gestational diabetes mellitus shall be made to identify
women at high risk of future diabetes and cardiovascular diseases (CVD).
• The principles for screening are recommended care.
• During the screening, people with high blood glucose need further diagnostic testing to
• Diagnosis should be based on FPG or capillary plasma glucose if only point-of-care
confirm the diagnosis. In contrast, screen-negative for diabetes should be retested every 3
testing is available.
years, especially for high-risk patients.
• Using FPG alone for diagnosis has limitations as it is less sensitive than 2-h OGTT in
• Paramedical personnel such as nurses or other trained workers should be included in any
Indians.
primary diabetes care team.
Prediabetes
• The principles of detection and management of prediabetes are the same as recommended
Prediabetes
care.
• People who screen-positive for prediabetes (FPG=100-125 mg/dL or 2-h PG in the 75-g
• Linkages to the healthcare system with the capacity to provide advice on lifestyle
OGTT=140-199 mg/dL or HbA1c=5.7%-6.4%) should be intervened with appropriate
modifications and alignment with ongoing support national programs available at
lifestyle modification.
community health centers where patients detected with prediabetes can be referred
• Screened and treated for modifiable risk factors for CVD such as hypertension,
are critical.
dyslipidemia, smoking, and alcohol consumption.
• Screening strategies should be linked to the healthcare system with the capacity to provide
advice on lifestyle modifications:
- May be aligned with ongoing support national programs available at community Background
health centers Conventionally, prevention is considered Primary, Secondary, and
- Patients with IGT, IFG should be referred to these support programs. Tertiary. Recently, an additional category has been recognized, which is
• People with prediabetes should modify their lifestyle, including: called ‘Primordial.’
- Attempts to lose 5%-10% of body weight if overweight or obese
- Participate in physical activity (e. g., walking) for at least 1-h daily if overweight or
obese and at least half an hour daily if weight is normal/controlled. Primordial prevention is defined as ‘existing at or from the beginning. It
- 6-8 hrs of sleep refers to efforts in early life (pre-pregnancy, pregnancy, and infancy) to
• Healthy lifestyle measures, including diet and physical activity, are equally crucial for non- reduce the risk of diabetes at a later age. It is expected to curtail the
obese patients with prediabetes. escalating epidemic of diabetes in future generations.
• People with prediabetes failing to achieve any benefit on lifestyle modifications after six
months may be initiated on oral antidiabetic agents (OADs):
- Metformin: In younger individuals with one or more additional risk factors for Primary prevention refers to the prevention of the onset of the disease by
diabetes, if overweight/obese and having IFG + IGT or IFG + HbA1c >5.7%, the modifying the risk factors such as obesity and insulin resistance.
addition of metformin (500 mg, twice daily) is recommended. Secondary prevention refers to early diagnosis and treatment of the dis-
- Alternatively, if metformin is not tolerated, alpha-glucosidase inhibitors (AGIs) such
as acarbose or voglibose may be initiated.
ease to prevent complications.
Tertiary prevention refers to limiting physical disability resulting from diabetes. Lower birth weight 38,39, shorter length, and higher ponderal index
40
complications and the institution of rehabilitation measures. have been associated with later diabetes. Rapid childhood growth in low-
birth-weight children is a decisive risk factor and embodies the double burden
In this section, we will be dealing with only primordial and primary of malnutrition during the life course of an individual 38–41. Only a few
prevention. Secondary and tertiary prevention will be handled in later studies have investigated the role of maternal nutrition in these associations,
sections. notably the Pune Maternal Nutrition Study. It highlighted an association of
maternal low Vit B12 and Vit D and higher folate status with later adiposity
Primordial prevention and insulin resistance in the offspring 42,43. Young adults (18-year-old) in this
Susceptibility to type 2 diabetes is usually considered to be ‘genetic’ study had an average BMI of 19 kg/m2, but 30 % (40% in males, 20% in
(non-modifiable), and the disease is said to be ‘precipitated’ by lifestyle females) had prediabetes (ADA criteria) 44. This was associated with shorter
factors (unhealthy diet, inactivity, stress, etc.) 22 Primary prevention strat- length, smaller head circumference at birth, and higher maternal fasting plas-
egies include treating high-risk individuals (middle-aged or elderly ma glucose during pregnancy, albeit within the normal range. Fasting plasma
prediabetic and obese) by improving lifestyle or with drugs 23. Post- glucose concentrations at 18y were also strongly predicted by more elevated
reproductive individuals are usually targeted, which does not benefit the fasting plasma glucose at 6 and 12 years of age, indicating that metabolic
offspring. As such, it is equivalent only to the treatment of early diabetes. abnormalities arise in early life. Glucose intolerance was predominantly driv-
en by lower beta-cell response to prevailing insulin resistance (lower dispo-
Indian Perspective sition index). Higher fasting plasma glucose at 6,12, and 18 years of age
Recent research has revealed an additional ‘non-genetic’ susceptibility to type predicted pregnancy hyperglycemia in females. In another follow-up in Pune,
2 diabetes which involves ‘epigenetic’ mechanisms and is therefore expected children born in diabetic pregnancies showed a high prevalence of diabetes
to be modifiable24. Epigenetic modifications are the basis of differentiation (5%) and prediabetes (37%) at age 45. All these findings point strongly
during intrauterine growth and development and are influenced by the intra- towards a role for early life nutrition (both under- and overnutrition) as a
uterine environment. These involve chemical alterations in DNA significant ‘programming’ exposure for future risk of diabetes and provide a
(methylation) without alteration in the base sequence of genes, histones (acet- background for interventions to improve the health of future generations.
ylation), or miRNA molecules, all of which influence gene expression. Thus, This is the central theme of the evolving science of Developmental Origins
a substantial part of epigenetic susceptibility to diabetes (and other non- of Health and Disease (DOHaD) 46.
communicable diseases (NCDs) develops during intra-uterine and early life Primordial prevention trials have already started in India. The first one is the
(‘Programming’). Within the intrauterine period, the most crucial window is Pune Rural Intervention in Young Adolescents (PRIYA) began in 2012. It
thought to be periconceptional (within a few days of conception) when the supplemented vitamin B12 with or without multi-micronutrients to adoles-
whole genome is demethylated and remethylated (epigenetic reprogram- cents in the Pune Maternal Nutrition Study 47. The intervention improved
ming). The intrauterine environment during this crucial window is a signif- micronutrient exposure of the offspring before conception and during preg-
icant influence on the epigenetic landscape of the conceptus 25. Significant nancy. The offspring's growth and development have improved compared to
influences on offspring’s epigenetic susceptibility include maternal nutrition their mothers. Cardiometabolic health will be tested during later childhood
(both under- and over-nutrition of macro- and micro-nutrients), metabolism but neurocognitive assessment between 2-4 years of age showed a beneficial
(especially diabetes), hormones, stress, environmental pollutants (including effect of vit B12 intervention on cognitive and language performance 48.
endocrine disruptors), etc. 26 Though most of the research has concentrated Participants in a neonatal Vitamin D supplementation trial are being
on maternal epigenetic transmission, recent evidence suggests that paternal followed-up in Delhi to study risk evolution for NCDs 49. An extensive
influences could also be necessary 27. community-based pre-conceptional intervention (HELTI-Einstein) is hap-
Interest in the epigenetic programming of diabetes exploded after Prof David pening in Mysore to improve nutrition, hygiene, and other aspects of mater-
Barker published a series of papers showing that lower birth weight increased nal health to reduce obesity-adiposity risk in children 50.
the risk of type 2 diabetes (thrifty phenotype hypothesis) 28. This was contrary The government of India has strengthened efforts to improve the health of
to the prevailing idea that fetal overnutrition in diabetic pregnancies was a children, adolescents, and pregnant women through a series of initiatives 51.
risk factor for later diabetes (fuel-mediated teratogenesis hypothesis of In addition to short-term improvement, these have the potential to influence
Pedersen and Freinkel) 29. It is clear that fetal undernutrition and overnutrition the long-term risk of diabetes and other NCDs in future generations. A
influence diabetes risk, albeit the contribution of the two varies in different pregnancy with a female child has an even more exciting prospect. The
populations. Interestingly, fetal undernutrition (protein and micronutrients) female fetus has all the ova in its ovary by 20 weeks of gestation 52.
and overnutrition (of calories, carbohydrates, and lipids) can co-exist, as seen Improvement in the mother’s health holds the promise of improving the
in pregnancies in rapidly transitioning societies and obese populations 30. health of at least the next two generations (a trans-generational rather than
India is a notable example. It’s the double capital of the world for the number inter-generational benefit). Let’s equip Abhimanyus of modern India to be
of low birth weight babies and the burden of diabetes. Maternal undernutri- better prepared to escape from the diabetes chakravyuha.
tion is common in many segments of society based on poverty, poor educa- In summary, recent research has discovered a novel possibility of an adjust-
tion, and gender bias, and gestational dysglycemia is not uncommon in these able epigenetic susceptibility to future diabetes. The most prominent window
women. Urban and higher socio-economic status women suffer from increas- for epigenetic programming of diabetes is in the periconceptional period and
ing obesity and pregnancy hyperglycemia accompanied by micronutrient covers pregnancy, lactation, and infancy (first 1000 days of life). Improving
deficiencies due to poor knowledge of healthy nutrition, challenging lifestyle, maternal health before, during, and after pregnancy has the potential to
and religious-cultural practices. In both these situations, the fetus is exposed curtail the escalating epidemic of diabetes in India. These facts must be
to a double burden of malnutrition. Indian babies are the smallest in the world widely disseminated to all the stakeholders, not the least to the policymakers,
(mean birth weight ~2.8 kg) but have a ‘thin-fat’ body composition (lower caregivers, and the target population. The government of India’s beneficial
lean mass and higher fat mass) compared to the heavier European babies 31. schemes has the potential to influence the health of future generations if
This reflects risk factors for future cardio-metabolic disease in the cord blood executed efficiently. Primordial is the best.
(more elevated insulin and leptin, as well as lower adiponectin concentra-
tions) 32. This comparative thin-fat phenotype of Indian neonates persists in Summary:
multi-generation migrant Indians 32 and continues in childhood 33, puberty, • Conventional ideas like primary prevention efforts in adults with predi-
34
and later life35–37. This reflects higher diabetes risk in Indians compared to abetes are tantamount equivalent of early diabetes. They mostly don’t
European populations at a younger age and a lower body mass index. help future generations because they are carried out in post-reproductive
Over the last three decades, many observational cohort studies in India have individuals They can be classified as ‘secondary prevention’ or ‘remis-
provided rich information on links between early life growth and later risk of sion’. Long-term follow-up in the Diabetes Prevention Programme of
the USA has shown a lack of effect on all-cause and cardiovascular Figure 1_Panel A: Cumulative incidence of diabetes – results of the
mortality and retinopathy. Cox proportional hazards model
• Primordial prevention refers to intergenerational and early life measures
to reduce risk factors for diabetes (beta-cell dysfunction, adiposity etc.)
and other non-communicable diseases (different organs and systems)
• The best window for primordial prevention is pre-conceptional when the
parents don’t know that pregnancy has occurred. Thus, improving the
nutrition and health of the young before marriage and pregnancy is crucial.
This is a societal and community-based effort, not a clinical intervention.
• Ancient Indian literature tells us the story of Abhimanyu, who learned in
utero how to enter Chakravyuh while listening to Krishna’s chat with
Subhadra. This is the first documented example of the ‘intrauterine
programming’ of the brain.
Primary prevention
Primary prevention is of utmost importance to reduce the number of new
cases of diabetes1. It is estimated that in India, more than 53% of the popu-
lation live with undiagnosed diabetes 53. The ICMR–INDIAB population-
based data reported the overall prevalence of diabetes and prediabetes in all 15
states of India to be 7.3% and 10.3%, respectively. Age, male gender, obesity,
hypertension, and family history of diabetes were the risk factors for diabetes
in urban and rural areas.54 An epidemiological survey across varied geograph-
ical locations in Tamil Nadu showed a sharp increase in the prevalence of
diabetes in 10 years (2006 -2016) 55. In 2016, the prevalence rates were
21.9% in the city, 20.3% in a town, and 13.4% in peri-urban villages Figure 1_Panel B: The hazard ratio (HR) and survival curve for the
(PUV). The corresponding prevalence of prediabetes also increased signifi- intervention versus the control groups – results of the Cox regression
cantly; 19%, 21% and 14.6% in the city, town and in the villages respectively. analysis.
In addition to the increasing age and family history of diabetes, waist circum- - The Indian SMS Study59 was done to study the effectiveness of mobile
ference was strongly associated with the increasing trend in the population 55. phone messaging in preventing T2D in men in India. Persons with
Diabetes among children and adolescents are also on the rise which could be persistent IGT were randomized to the control and intervention groups.
partly attributed to the rising rates of obesity and metabolic abnormalities 56. Control group received standard care advice only at baseline whereas
The need of the hour is to develop pragmatic, cost effective strategies for the intervention group received standard care and motivational text
screening and primary prevention and extend the benefits to the population at messages through mobile phones at least three times a week. Six month-
large to reduce substantial lifetime health costs by the society 57. The land- ly reviews were conducted for a period of 2 years. The control group (n
mark trials done in India have focused on lifestyle modification (LSM) as the = 266) showed a 27% conversion to diabetes in 2 years and the inter-
primary tool in prevention of T2DM (refs). They are briefly discussed below: vention group (n = 271) showed a reduced rate of 18% (Figure 1_Panel
B). Absolute risk reduction was 9% and the relative risk reduction com-
- The Indian Diabetes Prevention Programme-1 (IDPP-1)58 as a commu- pared to the control group was 36% which was highly significant. The
nity based randomized controlled trial designed to study whether primary number needed to treat to prevent one case of type 2 diabetes was 11
prevention of diabetes was feasible in Asian Indian population who were (95% CI 6–55).The reduction in the incidence was associated with im-
younger, leaner and more insulin resistant than the white populations. A proved dietary adherence which helped to increase the secretion of
30-month follow-up showed that the relative risk reductions were similar insulin and improvement in tissue insulin sensitivity. The study was
with the three interventions; LSM (29%), metformin (26%) and LSM + the first to prove the effect of mobile technology or mobile health in
metformin (28%) with no additional benefit or effectiveness in combining primary prevention of diabetes
both LSM and metformin (Figure 1_Panel A) - The Diabetes Community Lifestyle Improvement Program (DCLIP)60
was a randomized controlled trial among obese Indian adults with iso-
lated IGT, isolated impaired fasting glucose (iIFG) or IFG + IGT. The
control group received standard care advice and the intervention group
received aggressive LSM training through once weekly classes regard-
ing diet and exercise modeled on the basis of DPP study. In participants
with no significant improvement in blood glucose during the initial 4
months, metformin 500 mg was added twice daily. During 3-year fol-
low-up, 34.9% of control and 25.7% of intervention participants devel-
oped diabetes with a relative risk reduction of 32% (p = 0.014). A
significant observation was that 72% required metformin in addition
to lifestyle and the effectiveness was the least among iIFG.
Strategies have to be formulated considering the cultural, socio-economic

aspects and structure of the health care system. Many long-term studies
have proved primary prevention as the most potential and effective strat-
egy to combat the rising epidemic of T2DM56.
Considerations Relevant To The Development Of Screening Policy

The decision about conducting a screening programme should be based
on the following factors:
Epidemiological considerations
Glycosylated hemoglobin (HbA1c) as criteria for screening
• Clear evidence that screening is beneficial
• High prevalence of undiagnosed type 2 diabetes HbA1c has evolved as a valuable tool for screening and diagnosis of
• High prevalence of cardiovascular disease (CVD) risk and other complications diabetes and prediabetes and as a predictor of micro and macrovascular
amongst people with type 2 diabetes complications 67. Assays of HbA1c have multiple advantages over that of
Considerations of health system capacity blood glucose including its preanalytical and analytical stability, its inde-
• High capacity of health care system for screening
• High capacity of the health care system for effective clinical management of those who screen pendence of the prandial status, and the assays are well standardized with
positive high precision and accuracy. Presently the results are traceable to the
• High capacity of the health care system for supporting the psycho-social effects of screening Diabetes Control and Complications Trial (DCCT) assay values (mea-
• High capacity of the health care system to implement prevention strategies in individuals at
high risk of the future development of diabetes even those who screen negative on that
sured as %) 68 and can also be compared to the highly accurate
occasion International Federation of Clinical Chemistry (IFCC)-standardized
Economic consideration values (mmol/mol) 69. High cost of the assay and its instrumentation, lack
• Low cost of early detection
of awareness regarding its utility among the medical practitioners and the
• Low cost of clinical detection
assay interferences (hematological abnormalities, hemoglobinopathies,
and factors influencing erythropoiesis), limit its application. Healthcare
Adapted from Screening for Type 2 Diabetes - Report of a World Health professionals using the test should be aware of these limitations and use
Organization and International Diabetes Federation meeting 61 their discretion in interpreting the results.
Use of OGTT / blood glucose measure is a comparatively inexpensive,
sensitive index of hyperglycemia including impaired glucose homeosta-
Rationale And Evidence sis. However, several disadvantages such as wide biological variability,
poor reproducibility, influenced by acute factors such as stress, food, and
Opportunistic screening exercise, and also by some medications, are the main disadvantages of
There are many challenges involved in identifying people at risk. The ideal using blood glucose 69.
approach to primary prevention would be the upstream strategy wherein the In a recent study, Nanditha et al reported the concordance in the incidence
total population is targeted for prevention. This is not practical due to high of T2DM between cohorts with prediabetes, selected either by OGTT or
cost, availability of healthcare personnel and other resources. Therefore, a HbA1c. Cumulative incidence of T2DM was similar at 12 and 24 months
high-risk approach (downstream strategy) is followed commonly. This ap- assessed using the respective diagnostic criteria (25.3% with glucose and
proach was employed in the India prevention studies 62. 27.5% with HbA1c, p = 0.41 at 24 months). Both OGTT and HbA1c
were found to have similar utility and validity in identifying persons with
Risk assessment questionnaire IGT 70 .
Scoring systems can be applied for selecting persons for screening with
blood tests. Scoring (Risk Score) is based on non-invasive parameters Intermediate Hyperglycemia Or Impaired Glucose Regulation
such as age, family history of diabetes, body mass index (BMI), waist (Prediabetes)
circumference, physical activity and hypertension. This strategy has be- T2DM goes through several subclinical stages of abnormalities before its
come popular because it is non-invasive, least expensive and can be done clinical manifestations occur. Prediabetes is typically defined as blood
on a large scale. In the Indian Diabetes Prevention Programmes a com- glucose levels above normal, but below diabetes thresholds and presented
bination of risk score as the primary screening strategy, followed by a as either impaired fasting glucose (IFG) and / or impaired glucose toler-
glucose tolerance test / HbA1c to identify people with prediabetes has ance (IGT). Nearly 20–30% of people with IGT will also have IFG; and
been employed. about one-third of persons with IGT develop T2DM 15. In India, the
There are two risk scores specific for Asian Indians developed by Madras comparative prevalence (%) of IFG and IGT are 7.8% and 5.4 % respec-
Diabetes Research Foundation 63 and by Ramachandran et al tively 53. Recently, use of the term prediabetes has been criticized on the
64
[Annexure 1 and 2]. These risk scores are validated and are being used basis that not all people with this condition progress to T2DM and the
widely in our country. Risk score assessment is simple and can be applied term “intermediate hyperglycemia” is preferred.
at any worksite by paramedical personnel to help identify high risk Diagnosis of prediabetes or intermediate hyperglycemia
groups. Those at high-risk can be subjected to further blood testing. Impaired glucose tolerance is diagnosed when the 2-hour plasma glucose
value after 75 gm glucose intake is between 140–199 mg/dL. The values
Random plasma glucose level for IFG are a fasting plasma glucose concentration of ≥110 mg/dL, but
Screening using random capillary blood (RBG) glucose offers great <126 mg/dL 15. The ADA applies the same threshold for IGT, but uses a
benefits for testing large numbers, at low cost and in a short time. lower cut-off value for IFG (FPG of 100–125 mg/dL) 71. The ADA has
A large community-based screening program in India studied the also introduced the use of HbA1c levels of 5.7–6.4% (38.8–46.4
correlation of capillary RBG with oral glucose tolerance test mmol/mol) as a new category of high diabetes risk.
(OGTT) values to define cut-points for identifying diabetes and
prediabetes. It was suggested that a RBG value of >110 mg/dl Table 2: Diagnostic criteria for Prediabetes/ Intermediate hyperglycemia
(6.1 mmol/L) at screening can be recommended for definitive test-
ing 65 . Also, a RBG cut point of 140 mg/dl (7.8 mmol/L) Fasting plasma 2-h plasma glucose
corresponded to the 2h PG ≥ 200mg/dl (11.1 mmol/L) used in glucose (mg/dL)
diagnosis of diabetes 65. A similar observation was reported by (mg/dL)
another large study also from the same city which derived a RBG Normal glucose tolerance (NGT) <100* <140
Impaired fasting glucose (IFG) 100–125 Non-diabetes <200
cut-off value of 140.5 mg/dl (7.8 mmol/L) corresponding to an
Isolated IFG 100–125 <140
HbA1c value of 6.5% (48mmol/mol) (sensitivity 69%, specificity
Impaired glucose tolerance (IGT) Non-diabetes <126 140–199
83%, p<0.0001). The Area Under the Curve (AUC) was 0.823 ±
Isolated IGT <100 140–199
SE 0.16 (95% CI 0.792-0.854). RBG showed significant correlation Combined IFG/IGT 100–125 140–199
with HbA1c (r=0.40, p<0.0001) 66.
The panel endorse the IDF recommendation on the need to measure FPG
and perform OGTT based on random plasma glucose levels which are *The 100 mg/dL cut-off for IFG applies to guidance from the American
associated with the development of diabetes (2-h PG ≥200 mg/ dL) or Diabetes Association and the European Association for the Study of
prediabetes (2-h PG ≥140 to <200 mg/dL) Diabetes/European Society of Cardiology; the lower cut off for
diagnosing IFG is 110 mg/dL according to the World Health diabetes project, the Medical Education for Children/Adolescents for
Organization. Realistic Prevention of Obesity and Diabetes and for Healthy AGing
[MARG (The Path)], the media campaign for Prevention and Care of
The American Diabetes Association (ADA) recommends diagnosing Diabetes (Jagran Pehel) Programme, Childrens’ Health Education
“prediabetes” with HbA1c values between 5.7–6.4%. through Nutrition and Health Awareness (CHETNA)62.
Pregnancy as a critical target for diabetes prevention strategies Implementation of the Program by Simple and Pragmatic Methods
Hyperglycemia in pregnancy that includes existing diabetes and gesta- For successful implementation of any program, major changes are re-
tional diabetes (GDM) enhances the risk of diabetes in the offspring. The quired at personal, societal and community levels. Lifestyle intervention
increase in GDM poses challenges such as higher risk of diabetes among programs with the goals of decreasing excess weight, increasing physical
women and long-term consequences for the offspring. The offspring of activity, improving the quality of diet and refraining from unhealthy
mothers with GDM have increased risks of obesity, hypertension, diabe- habits (smoking, alcohol, and stress) have proven to be effective in re-
tes, and other non-communicable diseases 72. Given the high risk of ducing diabetes risk in those with IGT.
GDM and the potential trans-generational effects, universal screening
for GDM is necessitated. Randomized Controlled Trials on Primary Prevention
Long term prevention trials conducted in multiethnic population includ-
Screening strategies for children and adolescents ing the US Diabetes Prevention Program (DPP), Finnish Diabetes
Overweight (BMI >90 percentile) or obese children (BMI >99.5 percen- Prevention Study (DPS), Chinese Da Qing Study and the Indian
tile) with familial history of T2DM, and with associated risk factors such Diabetes Prevention Programme have shown that intervention with reg-
as insulin resistance, dyslipidemia, polycystic ovarian syndrome must be ulated diet, moderate physical activity or a combination of both results in
screened periodically. significant risk reduction in the incidence of diabetes. Two Japanese trials
Consistent with the recommendations for screening in adults, children at have also shown the efficacy of LSM in primary prevention of T2D 62.
substantial risk for the development of T2DM should also be tested. The
ADA recommends screening in overweight children and adolescents at
onset of puberty. The screening must be performed every 2 years using Sustained Effects of Prevention Strategies
fasting glucose or OGTT.
Extended Post-trial Analyses
Rescreening Extended trials such as the Chinese Da Qing study (CDQDPS), the
In a meta-analysis, investigators from multiple sites in India provided data Finnish Diabetes Prevention Study, the Diabetes Prevention Program
regarding patients with T2DM aged ≤30 years. The data, although col- Outcomes Study (DPPOS) in USA and the post-trial follow-up of the
lected from tertiary care centers, showed a prevalence of T2DM ranging Indian SMS study have indicated that the benefits of LSM can last for
from 1.1% to 4.7% (average, 2.76%) in patients aged ≤30 years. It was periods varying from 3 to 23 years. The risk reduction in the LSM group
also reported that 77.6 of these cases had a BMI of ≥23 kg/m2 73. The was attributed to sustained adherence to the lifestyle changes 62 . The
expert panel therefore suggests that the general population should be post-trial follow-up of the Indian SMS study investigated whether the
evaluated for the risk of diabetes by their health care provider on an beneficial effects of intervention persisted for an additional three years
annual basis beginning at age 25 years. Annual or more frequent testing after withdrawal of active intervention for two years. The analysis showed
should be considered in individuals with a history of prediabetes or pres- that there was sustained reduction in incidence of diabetes after cessation
ent with one or more risk factors that may predispose to development of of the intervention period. This indicated that many people continued to
diabetes. The panel opines that screening programs should be linked with practice improved lifestyle even after cessation of the supervised preven-
the healthcare system. tion program 74.
Paramedical personnel Clinical Guidelines on the use of Metformin in Prediabetes

Paramedical personnel play a key role as facilitators in imparting basic Evidence based studies showed that although metformin was less effec-
self-management skills to patients with diabetes and those at risk. They tive than lifestyle intervention, it was as effective as lifestyle intervention
can be actively involved in implementing diet and lifestyle changes, be- in certain groups of people. Participants who were young, those with a
havioral changes, weight management, pre-pregnancy counselling, and higher BMI, and women with a history of GDM were the most benefitted.
other preventive education. Nurses or other trained workers in primary Metformin promoted sustained weight loss and was associated with a
care and hospital outpatient settings can help identification of individuals significant reduction in the incidence of metabolic syndrome 75 .
at risk of diabetes Considering the effectiveness, safety, tolerability and minimal cost, met-
formin has been recommended by various expert groups such as the ADA
Awareness Creation and National Institute for Health and Care Excellence (NICE) for the
Education and creation of diabetes awareness are the primary require- therapeutic use for prediabetes alongside lifestyle modification. It is rec-
ments to successful implementation of primary prevention in diabetes. ommended for the young and obese, those with IFG, IGT or HbA1c
Several programs have been taken-up by organizations in different parts levels between 5.7–6.4%. 56.
of India; thePrevention, Awareness, Counselling and Evaluation (PACE)
Table 3: Summary of recommendations on use of metformin for

prevention of T2DM
Summary of recommendations on use of metformin for prevention of T2DM

ADA To add metformin to lifestyle intervention especially for those with BMI ≥35 kg/m2, those
aged <60 years, and women with prior GDM.
To monitor vitamin B12 periodically, especially where anaemia or peripheral neuropathy
is present.
ESC/EASD Does not recommend pharmacological intervention in people with non-diabetic
hyperglycemia. Recommends lifestyle changes to reduce the risk of new-onset diabetes
and cardiovascular risk in subjects with “prediabetes” or non-diabetic hyperglycaemia.
NICE To apply clinical judgement on the use of metformin to (continued support for) lifestyle
intervention for people with increasing HbA1c despite lifestyle intervention, or individuals
unable to take-up intensive lifestyle intervention.
To consider metformin especially if BMI is ≥35 kg/m2.
To discuss potential risks and benefits and nature of treatment.
To try metformin for 6–12 months and discontinue if there is no improvement in
glycaemia.
To monitor renal function initially and periodically (at least twice/per year).
Remission of Diabetes In the absence of HbA1c ,a FPG lower than 126 mg/dL (7.0 mmol/L) can
be used as an alternate criterion for remission. This approach has the dis-
Background And Evidence advantage of requiring fasting blood sample and sometimes significant
Diabetes management continues to evolve. The last few decades have variation in repeat measurements. Testing of 2-h plasma glucose following
shown a paradigm shift in our understanding of prevention and remission an OGTT is less desirable because of the complexity of doing the procedure
of type-2 diabetes. There are many studies supporting the concept of and variability. In addition, bariatric surgery which is one method of achiev-
diabetes remission including one of the earliest study from India by ing diabetes remission can alter the glycemic response to oral glucose .
Ramachandran et al. in 198776. Since then many definitions like “cure”,
“reversal”, “resolved”, “relapse” and “remission” have come up to define Follow up strategy:
the condition. Testing of HbA1c or another measure of glycemic control should be
The ADA international, multidisciplinary expert group with representa- performed at least yearly. Routine follow up and measurements at 6
tives from the American Diabetes Association, European Association for months and 12 months might be sufficient to identify remission and risk
the Study of Diabetes, Diabetes UK, the Endocrine Society, and the of relapse.
Diabetes Surgery Summit have recently proposed that “Diabetes remis- Even after a remission, the classic complications of diabetes both micro-
sion” is the most appropriate term 77. It strikes an appropriate balance, vascular and macrovascula can still occur 84. Hence, people in remission
noting that diabetes may not always be active and progressive yet imply- from diabetes should be advised to have regular retinal screening, tests of
ing that a notable improvement may not be permanent. An Indian expert renal function, foot evaluation, and measurement of blood pressure and
group have proposed a comprehensive definition for remission of Type 2 weight in addition to ongoing monitoring of HbA1c.
diabetes as a “healthy clinical state” characterized by achievement of
HBA1c below the targeted level, maintained for at least 6 months, with Pathophysiology
or without continued use of lifestyle modification and/or metformin, Conventionally, type 2 diabetes is explained by increased insulin
“provided that this is not due to complications, comorbid conditions or resistance and failure to meet the compensatory insulin demand
concomitant therapy”78. They have also proposed that the terminology of by the beta-cells due to progressive apoptosis (1). Histological
“remission of type 2 diabetes” should be clearly defined and used respon- studies have shown that beta-cell number decreased by 24–65%
sibly and sensibly79. The terminologies like “partial” and “complete” in type 2 diabetes (2).
remission with Hba1c level below the diagnostic threshold for diabetes Contrary to this understanding, the twin cycle hypothesis has its basis on
and below the diagnosis threshold of prediabetes respectively are more fat accumulation in the liver and pancreas being fundamental to the de-
confusing and should be used with caution. velopment of the disease (3). It is postulated that excess carbohydrate
Glycosylated hemoglobin (HbA1c )below 6.5%, and remaining at that (from diet) undergo de novo lipogenesis, stimulated by insulin secretion
level for at least 3 months without continuation of the usual ant hyper- which promotes fat accumulation in the liver. Individuals with relative
glycemic agents as the main defining measurement. In case of continued insulin resistance in muscle accumulate hepatic fat more readily because
use of glucose lowering drugs for other non-glycemic indications like use of higher plasma insulin levels. Hepatic insulin resistance would bring
of metformin in PCOS, SGLT2 inhibitors in CKD or heart failure or use about a tendency to increase plasma glucose levels resulting in compen-
of GLP1 RA for obesity, diabetes remission can not be ascertained or satory elevation of fasting plasma insulin levels. A vicious cycle of hy-
defined77. perinsulinemia and blunted suppression of hepatic glucose production
HbA1c measured must have a stringent quality control and standard- becomes established speeding the conversion of excess calories into fat
ization to international reference values 79–81. In selected situations producing very-low-density lipoprotein triglycerides (VLDL-TG). The
where the accuracy of HbA1c values are uncertain or less predictable export of VLDL-TG increase fat delivery to all tissues including the islets.
a FPG and /or CGM may be used to assess the correlation between The increased exposure to intra and ectopic fat by the pancreatic islets
mean glucose and HbA1c and identify patterns outside the usual impairs acute insulin secretion in response to ingested food, and at a
range of normal 82,83. certain point, postprandial hyperglycaemia develop. Constant
hyperglycaemic status further increase insulin secretion rates, resulting in B. Bariatric Surgery
increased hepatic lipogenesis, spinning the liver cycle faster and driving Bariatric surgery has shown to reverse T2DM and change outcomes for
on the pancreas cycle. The excess fat exposure causes beta cells to de- obese patients for over 30 years85 Reduction in post-prandial fatty acid
differentiate causing inability (downregulation of genes controlling insu- intermediates (that inhibit glucose metabolism) following bariatric sur-
lin production) to secrete insulin leading to clinical onset of diabetes (3). gery result in utilisation of glucose or cellular fat storage. Remission of
The aetiology of the disease is therefore explained by hepatic insulin glycemia occurs even before weight loss after bariatric surgery implicat-
resistance and beta cell dysfunction rather than its deterioration which ing some hormonal mechanisms.
could be reversed by major calorie restriction and substantial weight loss Bariatric surgery causes alterations in gastrointestinal hormone release,
especially in those who are obese or overweight. Interestingly, studies including ghrelin, leptin, cholecystokinin, peptide YY, and in particular,
like the Indian Diabetes Prevention Programme from India have shown glucagon-like peptide 1 (GLP-1), which may correct feeding behaviour
that the same mechanisms including improvement in insulin sensitivity via the gut-brain axis in addition to sustaining euglycaemia. Studies have
could occur with lifestyle modification even in non-obese individuals, shown that postprandial levels of endogenous GLP-1 after bariatric sur-
without clinically significant weight reduction (4). The chance of achiev- gery can be 10 to 20 times higher compared with before surgery. These
ing remission through these strategies is largely determined by the beta hormonal changes occur in response to weight loss and depend upon type
cells to recover to its maximal capacity and function. Many studies have of surgical procedure. Interestingly, bariatric surgery causes dramatic
been conducted to provide the evidence base to this hypothesis (5-7). changes in the gut microbiome, with reversion from an obesogenic profile
Evidence Based studies: to lean.
Systematic reviews showed that bariatric surgery could initially reverse
A. Nutritional Basis T2DM for 58% to 95% of patients86.The prospective Swedish Obese
Dietary recommendations play a crucial role in remission of diabetes by Subjects study reported remission rates of T2DM at 2, 10 and 15 years
aiding in weight loss. With relevance to modifying the existing dietary of follow-up as 72.3%, 38.1% and 30.4%, respectively87.In a prospective
pattern, various strategies have been put forth; a low carbohydrate or Utah study of RYGB in class II obesity remission rate for diabetes were
calorie diet, restricted feeding time and improving dietary quality (8). 75% and 62% at 2 and 6 years 88 . The Surgical Treatment and
Studies in different populations have shown that both low calorie and low Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE)
carbohydrate diets are effective for weight loss (9). In comparison to low was a landmark study designed to examine the efficacy of bariatric sur-
fat diets, greater weight loss was achieved with low carbohydrate diets up gery plus medical management compared to optimal medical manage-
to one year with a modest difference of around 1 kg body weight (10). ment alone for glycaemic control among poorly controlled T2DM indi-
Moreover, low or very low carbohydrate diets are preferred over fats as viduals. randomized in the RYGB, VSG and control arms in a 1:1:1 ratio.
carbohydrates are the primary contributor to post-prandial glycaemia. In Remission rates were 42%, 27%, and 0% at year 1, 39%, 20%, 0% at 3
another study with intensive follow-up, sustained weight loss of 12 kg at years and 22.4%, 14.9%, 0% at 5 years respectively for RYGB, VSG and
two years was reported with a very low carbohydrate diet (11). Similarly, conventional89.
a study in UK, reported a decrease in median weight of 8.3 kg at a two CROSSROADS trial90 (Calorie Reduction Or Surgery: Seeking to
year follow-up by using a low carbohydrate diet (50-130 g/day) (12). Reduce Obesity And Diabetes Study) compared the effects of RYGB
The definition of a low carbohydrate diet varies widely across studies versus an intensive medical therapy combined with lifestyle intervention
from <45% of total energy intake to ketogenic levels of <10%. (11,13). on T2DM remission (defined as HbA1c < 6% off antidiabetic medica-
To avoid ambiguity, the following standard categorization is used (14). tion), among individuals with T2DM and a baseline BMI ranging be-
tween 30 and 45 kg/m2. T2DM remission rates were 60% and 5.9% for
• Very low carbohydrate: 20 to 50 g/day (≤10% of energy, based on 2000 the RYGB and non-surgical arms, respectively.
kcal/ day) Another RCT by Courcoulas et al.91 compared the effects of RYGB,
• Low carbohydrate: >50 to <130 (>10% to<26%) AGB and non-surgical treatment on T2DM remission (as defined by
• Moderate carbohydrate: 130 to 230 (26%to 45%) the ADA) among individuals with T2DM and obesity grades I-II. The
• High carbohydrate >230 (>45%) rates of partial and complete T2DM remission after 1 year of follow up
were 50/17%, 27/25% and 0/0% for the RYGB, AGB and medically
Studies from India have also reported remission following a low calorie treated arms, respectively. After 3 years of follow up, remission (partial
liquid diet (15). A cohort of young adults with recently diagnosed T2DM and complete) within the cohort was 40%, 29% and 0% for RYGB, AGB
showed 75% remission at three months and 69% at two years; HbA1c and the control group, respectively. In a meta-analysis of twenty-six stud-
was <5.7% in 53% of participants at three months and in 47% at two ies in patients with BMI <30 73 diabetes remission was reported in 43%.
years; 22% had a value of 5.7-6.5% at both time points (16). A study from The Second Diabetes Surgery Summit 2016 produced recommendations
the Middle East observed remission in 61% of those allocated to total diet which were endorsed by 45 national medical societies worldwide, to use
replacement and lifestyle intervention (17). In persons with prediabetes, bariatric surgery as a treatment option for T2DM in adults with body mass
remission at 6 months has been shown in an Indian cohort with significant index >40, or >35 kg/m2 in those with obesity-related co-morbidities.
improvements in insulin resistance and beta cell function by intensive These guidelines were based on the observation that there was uniform
lifestyle modification (4,18). improvement in glycaemic control after any bariatric operation 92.IFSO-
Traditional practices such as intermittent fasting, abstinence of food in- APC Consensus statements 2011 suggest lower threshold i.e. BMI ≥ 35
take on certain days, time restricted feeding (eating within a 6 to 8 hour with or without co-morbidities and BMI ≥ 30 with T2DM or metabolic
window each day) are effective strategies for weight loss by lowering the syndrome for patients who are inadequately controlled by lifestyle alter-
calorie intake by 25% (500 – 700 calories) (19). However, long-term nations and medical treatment for acceptable Asian candidates for bariat-
studies are required to establish its effectiveness on remission. ric surgery.
Moreover, reducing carbohydrates indiscriminately may lead to loss of The surgical approach may be considered as a non-primary alternative to
consumption of fibre and wholegrain. Advice on foods consumed within treat inadequately controlled T2DM, or metabolic syndrome, for suitable
theregular dietary pattern may facilitate better longer term adherence. Asian candidates with BMI ≥ 27.5. OSSI upholds the BMI criteria for
Studies indicate that maintaining weight loss over 10 years without bariatric and metabolic surgery of 2011 IFSO-APC guidelines. In addi-
weight regain is feasible but requires sustained dietary change, regular tion waist circumference of ≥ 80 cm in females and ≥ 90 cm in males was
physical activity and frequent self-weighing (20). Education, dietary added along with obesity related co-morbidities for surgery93.
guidelines and empowerment to make healthy food choices should be Not all individuals with T2DM experience remission after bariatric sur-
implemented at a population level. gery. Unsurprisingly, the improvement of glycemic control relates to the
degree of weight loss after surgery, while less profound weight loss dur- glycemic remission. In a meta-analysis, short-term intensive insulin ther-
ing the first postoperative year and greater weight regain may predict apy was found to significantly improve islet function and induce remis-
T2DM relapse. 76 sion in 46% of patients at 12 months, and 42% at 24 months. This effect is
ABCD score (age, BMI, c-peptide, duration of diabetes) and DiaRem weight-loss independent, without diet restrictions. Beta-cell re-differenti-
score models can predict remission of diabetes after surgery. Broadly ation was considered the important underlying mechanism for the treat-
long-term outcomes from bariatric surgery depend upon type of surgical ment effect.
procedure and patient baseline characteristics like weight, age, duration of Jennings et al98 found a triple therapy of metformin, pioglitazone and
diabetes and status of insulin secretory reserve (those already on insulin repaglinide to be effective for reversing newly diagnosed T2DM patients.
have low rate of remission). Gastric bypass which employs restrictive and The drugs were given at maximum tolerated doses and then tapered
malabsorption strategies is the most effective in inducing remission of according to results.
diabetes followed by sleeve gastrectomy, and gastric banding.94 5 years Anti-obesity drug orlistat, a peripheral lipase inhibitor and a calorie re-
long term data put remission rates for T2DM patients after sleeve gastrec- striction mimetic (CRM), has shown potential to improve glycemic pa-
tomy as good as those for gastric bypass.95 Other methods like laparo- rameters. Orlistat could be considered a type of drug that otherwise
scopic gastric banding, gastric balloons and more recently “pill balloons” mimics the mechanism of action, effects, and long-term outcome noted
cause weight loss and remission of diabetes but long term data on diabetes with calorie restriction, without actually causing calorie restriction or lack
is scant.79 of food intake.
There are complications involved with bariatric surgery. In clinical trials, High dose GLP-1 analogues (semaglutide) GLP-1/GIP dual analogues
mortality rate within one month and after was 0.08% and 0.31% respec- (tirzepatide) have been effective in controlling hyperglycemia and in
tively. Significant complications include anastomotic leak or haemor- decreasing weight. Their role in remission of diabetes is yet to be tested.
rhage, dumping syndrome, worsening acid reflux, marginal ulceration,
and micronutrient deficiencies. For these reasons each patient risks from MEDICAL NUTRITION THERAPY (MNT) AND LIFESTYLE
obesity and co-morbidities must be weighed up against the risks associ- MODIFICATION
ated with bariatric surgery. 80
Revisional surgery for recurrent metabolic disease has shown 65%-100% Recommendation
improvement of diabetes depending upon index surgery and subsequent
reconstruction. Recommended Care
Revisional bariatric surgery has been shown to have utility for recurrent MNT
metabolic disease, especially T2DM. Depending on the index surgery and • The nutrition chart and support should be made by a trained nutritionist and a
subsequent reconstruction, improvement of diabetes was seen in 65– physician/diabetologist.
• It should be based on TAF- Type, Amount, and Frequency
100% of patients.
Further mechanistic research and much larger prospective randomized
Carbohydrates
studies would be needed to identify the optimal treatment strategies for
• Carbohydrate content should be limited to 50%-60% of total calorie intake.
post-bariatric weight regain and relapse of T2DM with residual or recur- • Complex carbohydrates should be preferred over refined products.
rent metabolic disease.87 • The low glycaemic index (GI) and low glycaemic load (GL) foods should be
chosen.
Pharmacotherapy • The quantity of rice (GI: 73) should be limited as it has high GI; Brown rice (GI:
68) should be preferred over white rice. (Millets are another alternative)
Most T2DM guidelines have focused on the pharmacological manage- • Fiber intake: 25-40 gm per day.
ment of hyperglycemia, rather than weight loss, which was always a part
Proteins
of core management.96 The increasing use of hyperphagic drugs like • Protein intake should be maintained at about 15% of the total calories. The
insulin and sulphonylureas was a further contradiction. quantities of protein intake depend on age, sarcopenia, and renal dysfunction.
Logically thinking, pharmacotherapy alone cannot address underlying • Non-vegetarian foods are sources of high-quality protein. However, intake of red
unhealthy lifestyles leading to overweight. Overweight/obesity is a chron- meat should be avoided.
ic problem strongly driven by genetic factors with a high risk of relapse, Fats
and in addition . obesogenic addictive environment. T2DM is usually a • Fat intake should be limited (<30% of total calorie intake), with most sources being
progressive disease and current therapies are glucocentric not addressing from nuts and seeds.
the problem of visceral fat. Perhaps, the most depressing data by Kaiser • Oils with high mono unsaturated fatty acid (MUFA) and polyunsaturated fatty acid
(PUFA) should be used.
Permanente study that found only a 0.23% remission rate with best prac- • Use of 2 or more vegetable oils is recommended in rotation.
tice standard care.97 • For non-vegetarians, 100-200 g of fish/week is advised as a good source of
In fact, the feasibility of reversing T2DM with pharmacotherapy has been PUFA, and for vegetarians, vegetable oils (soybean/ safflower/sunflower),
demonstrated in numerous studies and with different medications. Studies walnuts, and flaxseeds are recommended. (Peanut oil and mustard oils are
have shown that, when implemented early in the course of T2DM (ideally suitable based on their fatty acid composition)
• Avoid consuming foods high in saturated fat (butter, coconut oil, margarine, and
less than 2 years), intensive insulin therapy for 2–3 weeks can induce a
ghee).
• Saturated fatty acids (SFAs) intake should be less than 10% of total calories/day
(<7% for individuals having high triglycerides).
• Use of partially hydrogenated vegetable oils (Vanaspati) as the cooking medium
should be avoided.
• Reheating and refrying of cooking oils should be avoided.
Food groups and patterns

• A diet rich in fruits, leafy vegetables, nuts, fiber, whole grains, and unsaturated fat
is preferred. The plate should include pulses, legumes, unprocessed vegetables, and
low-fat dairy.
• Portion size
- Food plate should have vegetables and fruits as the main constituent (50%),
both raw and cooked with a variety of vegetables over the week, adding
diversity of vegetarian foods to increase intake of phytonutrients
• Extreme diets, including low-carbohydrate ketogenic, must be planned and
executed following consultation with a physician and nutritionist and for a short
period.
• Overall salt consumption should be <5 g/day (with sodium consumption <2300
mg/day).
• Avoid or decrease alcohol intake.
• Smoking cessation should be advised to all. Smoking cessation therapies may be
provided under observation for patients who wish to quit in a step-wise manner
• Sugar-sweetened beverages are best avoided.
• Artificial sweeteners should be avoided as they alter the diversity of the gut
microbiome and can increase insulin resistance.
• Meal plans with strategic meal replacements (partial or complete) may be an option
under supervision when feasible.
• Indian fast foods-Street foods like kachori and samosa should be avoided.
• The advocation of fiber-rich fermented food.
Lifestyle modifications
• Physicians and diabetes educators could impart recommended care.
• Careful instructions should be given for initiating the exercise program. Help from
a trained exercise therapist can be taken.
• Lifestyle advice should be given to all people with T2DM at diagnosis. It should be
an effective option for controlling diabetes and increasing CV fitness at all ages
and stages of diabetes.
Limited Care
• Nutritional counseling may be provided by health care providers (HCPs) trained in

nutrition therapy, not necessarily by an accredited dietician nutritionist.
• Overall, reduced consumption of simple carbohydrates, sugar, and fried foods and higher
consumption of complex carbohydrates with high protein intake are recommended.
• Salt intake should be in moderation.
• Encourage increased duration and frequency of physical activity (where needed based on
comorbidities and physical status complications.
• Mass awareness campaigns for a healthy diet and lifestyle should be conducted.
Background
An unhealthy diet and a sedentary lifestyle have been identified as mod-
ifiable risk factors in T2DM. Rapid urbanization and westernization with
rampant availability of fast foods and processed foods that contain high
amounts of refined carbohydrates, saturated fats, added sugars, and low
fiber has dramatically changed the local food environment in India.99
Along with increasing physical inactivity, these adverse dietary changes
have been associated with detrimental influences on the onset and pro-
gression of T2DM in India.100–102 MNT is a systematic approach to
optimizing dietary intake to achieve metabolic control and maximize
favorable treatment outcomes in T2DM. Conceptually, MNT involves
counseling and recommendations from a registered dietician (RD) under
the regular supervision of consulting diabetologists.
Current global clinical practice guidelines for T2DM from the ADA,
American Association of Clinical Endocrinologists (AACE), and IDF advo-
cate the importance of integrating MNT in the management of T2DM as first-
line therapy and provide consistent recommendations for day-to-day nutri- carbohydrate, high-fiber diet in promoting weight loss, improving glycemic
tional requirements.103,104 MNT is a lifestyle transforming process beyond control, and lowering CV risk.117–120 High carbohydrate diets should com-
calorie restriction and portion control. Implementation of MNT in India is prise significant amounts of unrefined carbohydrates and fiber such as le-
challenging owing to its cultural and culinary diversity. Consumption of high gumes, whole grains, unprocessed vegetables, and fruits.100,121,122 High car-
amounts of carbohydrates, including ghee-laden sweets loaded with sugar or bohydrate diet regimens in T2DM patients have been associated with favor-
jaggery, is inherent to the standard Indian diet and closely linked to cultural able weight loss and reductions in plasma glucose, HbA1c, and LDL levels
and religious traditions. Thus escalating the challenges of restricting carbohy- with good adherence and sustainability, comparable with low carbohydrate
drate intake. Therefore, designing individualized diet plans as a part of MNT diets. The concern of the possible untoward effect of a high carbohydrate diet
in India should consider regional, cultural, economic, and agricultural factors, on the lipid profile (increase in triglycerides and reductions in HDL) and CV
as all these have a marked influence on the acceptance of MNT by the patient. risk can be mitigated by lowering the glycemic index of diets incorporating
fiber-rich foods.114
Role of medical nutrition therapy in prevention and management Cross-sectional data from the CURES suggests that Indians consume high
Dietary counseling, adherence to a healthful, calorie-restricted diet, and reg- amounts of refined grains (~47% of total calories), which is associated with
ular exercise have lower rates of incident diabetes in Indian men with im- significant increases in waist circumference (p<0.0001), systolic blood pres-
paired glucose tolerance. Community health programs and implementation sure (p<0.0001), diastolic blood pressure (p=0.03), fasting blood glucose
of MNT-based model meals in rural and urban populations in South and (p=0.007), serum triglyceride (p<0.0001), lower HDL (p<0.0001), and insu-
North India have shown favorable changes in dietary patterns and parame- lin resistance (p<0.001). Further, Indians who consumed refined grains were
ters, including BMI, waist circumference, fasting blood glucose, and so more predisposed to develop the metabolic syndrome (odds ratio [OR]: 7.83;
on.105–107 A stepwise Diabetes Prevention Program lowered the 3-year risk 95% confidence interval [CI]: 4.72, 12.99) and insulin resistance versus those
of diabetes by 32% (95% CI: 7, 50) in obese Asian Indian adults with any who consumed lower quantities.123
form of prediabetes.108 These studies, including a few others involving In an assessment of the quality and type of carbohydrates in a subset of
Indians with risk factors for diabetes, reported benefits of dietary approaches patients from the CURES study, consumption of refined grain (OR: 5.31;
such as high consumption of fiber-rich foods, high-protein meal replace- 95% CI: 2.98, 9.45; p<0.001), total carbohydrate (OR: 4.98; 95% CI:
ments, or replacement of polished white rice with whole grain brown rice, 2.69, 9.19; p<0.001), GL (OR: 4.25; 95% CI: 2.33, 7.77; p<0.001), and
and increased intake of fruits and vegetables.109,110 GI (OR: 2.51; 95% CI: 1.42, 4.43; p=0.006) positively correlated with the
The prescription for diet should be given in the form of TAF: type, risk of T2DM. In contrast, a high dietary fiber intake showed an inverse
amount, and frequency of foods. correlation with T2DM (OR: 0.31; 95 % CI: 0.15, 0.62; p<0·001).122
The landmark lifestyle intervention program, “Look Ahead,” examined Additional analysis of the data from the CURES study population re-
the effects of a calorie-restricted diet and reduced intake of high-GI car- vealed the detrimental dietary habits among South Indian adults (daily
bohydrates such as sugar, flavored beverages, and high-calorie snacks on energy intake: carbohydrates [64%], fat [24%], protein [12%]) that esca-
glycemic control and prevention of CV complications. At 11 years, par- lates the risk of T2DM. It was observed that refined cereals contributed to
ticipants benefited from the controlled diet. They had an average weight nearly 46% of total energy intake, followed by visible fats and oils
loss of 5% and substantial improvements in HbA1c levels, blood pres- (12.4%), pulses and legumes (7.8%), and information of micronutrient-
sure, lipid profile, and overall fitness and well-being.111 In a year-long rich foods (fruits, vegetables, fish, etc.) was inadequate and below the
prospective study from India, individuals with T2DM, randomized to recommended standards of FAO/WHO.124
MNT, achieved a significant lowering of HbA1c and all lipid parameters, Given that carbohydrates are an inherent part of the staple Indian diet and
especially triglyceride levels. This study involved 20 dieticians and re- Indians habitually tend to consume high amounts of carbohydrates, improv-
ported the success of a guided, evidence-based, individualized MNT ver- ing the quality of carbohydrates in the diet by replacing high-GI carbohy-
sus usual diabetes care.112 Based on these clinically relevant observations drates with fiber-rich, low GI counterparts.125 It was observed that consump-
in the Indian population, the RSSDI recommends the adoption of tion of brown rice significantly reduced 24-h glycemic response 24-h
dietician-guided MNT as an integral component of diabetes management. (p=0.02) and fasting insulin response (p=0.0001) in overweight Asian
The MNT and lifestyle modifications should be individualized based on Indians.126 Replacement of white rice with brown rice was fo be feasible
disease profile, age, sociocultural factors, economic status, and the pres- and culturally appropriate in Indian over-weight Indians and correlated with a
ence of sarcopenia and organ dysfunction. lower risk of T2DM.127 Fortification of humble Indian dishes with fiber-rich
alternatives, for example, adding soluble fiber in the form of oats in up or
Rationale And Evidence improving the glycemic quality of Indian flatbreads (Rotis or chapattis) by
adding wheat flour with soluble viscous fibers and legume flour have shown
Carbohydrate monitoring favorable outcomes on the lipid profile and postprandial glucose and insulin
Meal planning approaches should include carbohydrate counting, ex- responses in T2DM patients.128–131
changes, or experience-based estimation and measurement of GI and Sugar and sugar-sweetened beverages increase the dietary GL. Overall, the
GL to monitor the number of carbohydrates in food and understand the consumption of sugar (25.0 kg/capita) among Indians exceeds the average
physiological effects of high-carbohydrate diets.113,114 global annual per capita consumption (23.7 kg). Consumption of sweets,
sweetened beverages (e. g., lassi, cameras), and other addition of sugars in
High-carbohydrate, low-fat diets curries, gravies, etc. have customary and regional importance in India.132 In
Although there is a dichotomy in recommendations concerning high-or urban South India, the added sugars in hot beverages (tea or coffee) majorly
low-carbohydrate diets, historical data from India suggest the metabolic contribute to sugar intake and account for around 3.6% of total GL.122
benefits of high-carbohydrate, high-fiber, low-fat diets as opposed to a However, fermented foods or beverages produced through controlled
high-fat, low-carbohydrate diet.115,116 microbial growth help to improve the gut microbiome and may improve
glycemic control.133,134
Recommendation for MNT in patients with T2DM The low-carbohydrate, ketogenic diet
Low-carbohydrate diets may particularly benefit patients with impaired
MNT: Medical nutrition therapy; T2DM glucose tolerance and obesity. However, these diets are high in fats and
In patients with Type 2 diabetes mellitus, high carbohydrate, high-fiber, low proteins to balance the macronutrient content. Therefore, while adopting
fat diets are recommended as opposed to a high-fat, low carbohydrate di- such diets, fat intake should occur mainly in the form of MUFA with a
et.115,116 Recent studies support the implementation of a long-term high- parallel decrease in saturated fatty acids (SFAs) and trans fatty acids
(TFAs). As the metabolic pathways of carbohydrates and fats are intervention by replacing refined cooking oils with those containing a high
interlinked, low carbohydrate diets high in fats and protein are associated percentage of MUFA (canola and olive oil) in Asian Indians with non-
with long-term effects such as ketosis, adverse lipid, and renal alcoholic fatty liver disease was associated with a significant reduction in
outcomes.135Evidence suggests that T2DM patients on a low carbohy- body weight and BMI (p<0.01, olive oil), improvements in fasting insulin
drate diet achieve favorable outcomes due to reduced energy intake and level and insulin resistance and β-cell function by homeostasis model of
prolonged calorie restriction, not low carbohydrate intake. Obese T2DM assessment (p<0.001, olive oil), increase in high-density lipoprotein level
patients should therefore consider switching to a low-carbohydrate diet (p=0.004, olive oil), and decrease in fasting blood glucose (p=0.03) and
designed based on calorie restriction and regulated information of fats to triglyceride (p=0.02) level (in canola group).149An increase in use of saturat-
reduce the incidence of T2DM and myocardial infarction.136,137 These ed fat, low intake of n-3 PUFAs, and an increase in TFAs were observed
diets should be considered for a limited period only. In a small study, among Indian patients with T2DM and obesity, and it is recommended that
overweight patients with T2DM were randomized to a very low carbo- improve the quality of fats in the diet (more MUFAs and omega-3 PUFAs)
hydrate ketogenic diet, and lifestyle modifications such as physical activ- would be beneficial in T2DM.150,151 Reheating/frying or reusing oils at high
ity, sleep, etc. had significantly improved their glycemic control temperatures, a common practice in India should be avoided as it induces
(p=0.002) and lost more weight (p<0.001) than individuals on a conven- chemical changes that increase the amounts of harmful TFAs, which signif-
tional, low-fat diabetes diet program.138In another similarly designed ran- icantly elevate the risk of CV complications in T2DM patients.152,153
domized controlled trial, overweight individuals with T2DM or elevated
HbA1c levels on a very low carbohydrate ketogenic diet for 12 months Fiber and diabetes mellitus
had significant reductions in HbA1c levels (p=0.007) and body weight Increasing the intake of dietary fibers is known to have a favorable effect on
(p<0.01) than participants on a moderate-carbohydrate, calorie-restricted, overall metabolic health. A high intake of dietary fiber, particularly of the
low-fat diet.139In a 24-week interventional study, a low-carbohydrate soluble type, above the level recommended by the ADA, improves glycemic
ketogenic diet in patients with T2DM favorably improved body weight, control, decreases hyperinsulinemia, and lowers plasma lipid concentrations
glycemic, and lipid profiles in patients with T2DM as compared with in patients with type 2 diabetes. Soluble fiber from oats, beans, some nuts and
patients on a low-calorie diet.140 seeds help in regulation of Blood sugar levels, whereas insoluble fiber from
whole grains, green leafy vegetables and fruits with edible peels helpsimprove
The low glycemic index of pulses and pulse-incorporated cereal foods the bowel movement.154 Fiber-rich foods contain complex carbohydrates
Compared with other Western or Asian diets, traditional Indian diets resistant to digestion and thereby reduce glucose absorption and insulin se-
comprising dal, roti, rice, and curry provide a wholesome supply of bal- cretion.155–157In overweight or obese patients with T2DM, a low glycemic
anced, mixed nutrients. The mix of various pulses and legumes in a index and high-fiber diet significantly (p<0.001) reduce glucose and insulin
standard Indian meal offers variations in the glycemic and insulinemic area under the curve compared with high-glycemic and high carbohydrate
indices attributed to the nature of available and non-available (non- diets. The favorable effects on postprandial glucose and insulinemia were
starchy polysaccharides) carbohydrates in the foods and alterations in sustained for an entire day.158Consumption of high-carbohydrate, low-GI
rates of carbohydrate absorption.141,142 Rice or wheat-based starchy high diets that contain high proportions of dietary fibers also mitigate the risk of
GI diets reduce the glycemic index and bring satiety and an adequate an increase in serum triglyceride levels, a common consequence of a high-
supply of calories. Meals with mixed sources of Cereals, pulses, and carbohydrate diet.114 Intake of soluble and insoluble fibers has been associ-
legumes contribute to the regulation of insulin and glycemic responses. ated with increased post-meal satiety and decreased consequent hunger epi-
Combining acarbose in regular daily diets was associated with a signifi- sodes.159 In a randomized, cross-over study in 56 healthy Indian participants,
cant decline in postprandial blood glucose in T2DM patients, including consumption of flatbreads with the addition of fibrous flour such as chickpea
those who failed prior treatment with OADs.143 Similarly, consumption (15%) and guar gum (3% or 4%) to wheat flour significantly reduced post-
of adai dosa (a type of Indian pancake with 75% pulses and 25% cereals) prandial glucose (p<0.01) and postprandial insulin (p<0.0001) when com-
versus a standard diet (75% cereal and 25% pulses) was associated with a pared with flatbreads made from control flour (100% wheat flour).128In a
reduction in body weight and significant (p<0.01) lowering of HbA1c.144 dietary assessment study in urban Asian Indians with T2DM, low consump-
Inclusion of nuts (almond, walnuts, cashews, pistachios, hazelnuts) in a tion of dietary fibers (<29 g/day) was associated with a higher prevalence of
diet corresponding to approximately 56 g (1/2 cup) of nuts was associated hypercholesterolemia (p=0.01) and higher LDL (p=0.001) than individuals
with a significant reduction in HbA1c (mean difference: − 0.07% [95% with a greater median intake of fibers.160 In a randomized study, daily con-
CI: −0.10, −0.03%]; p=0.0003) and fasting glucose (mean difference: sumption of 3 g of soluble fiber from 70 g of oats in the form of porridge or up
−0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; p=0.03) In individuals for 28 days in mildly hypercholesterolemic Asian Indians was associated with
with T2DM versus isocaloric diets without nuts. The improvement was a significant reduction in serum cholesterol (p<0.02) and LDL (p<0.04) ver-
mainly attributed to the lowering of GI due to replacement by nuts.145In sus the control group (routine diet).129From a meta-analysis of 17 prospective
an analysis of dietary patterns in India, diets rich in rice and pulses were cohort studies, an inverse relation was observed between dietary intake and
associated with a lower risk of diabetes versus diet models with more risk of T2DM, based on which it was recommended that intake of 25 g/day
sweets and snacks.146 Legumes such as chickpeas are also low glycemic total dietary fiber might be optimal for T2DM patients’ maintenance.161
foods and, when substituted for a similar serving of egg, baked potato,
bread, or rice, lower the risk of T2DM. They may be beneficial in elderly Physical activity
individuals with CV risk.147 The International Physical Activity Questionnaire-Long Form and accel-
erometer can be used to measure and monitor the intensity of physical
Consumption of oils among the Indian population activity.162 The intensity of exercise can be measured via the Talk test163
In the rural South Indian population from the CURES study, the highest because of its ease of use with the patients.
intake of fats directly correlated with the risk of abdominal obesity
(p<0.001), hypertension (p=0.04), and impaired fasting glucose (p=0.01). • Light intensity: talk and sing comfortably
In particular, sunflower oil was most detrimental compared to traditional oils • Moderate intensity: Talk with some effort, but not sing
and palm olein.148A higher percentage of linoleic acid PUFA in sunflower oil • Vigorous intensity: Cannot talk comfortably
was correlated with the risk of metabolic syndrome. Supporting this finding,
the risk of metabolic syndrome was higher among users of sunflower oil Physical inactivity is regarded as a major risk factor for T2DM, and
(30.7%) versus palm olein (23.2%) or traditional (groundnut or sesame) oil evidence suggests that adequate physical activity may reduce the risk
(17.1%, p<0.001) in Asian Indians. 52 The observations from these studies by up to 27%.125,164 Exercise prescriptions should follow the FITT-VP
are preliminary and should be further investigated. Managing dietary principle: frequency, intensity, time, type, volume ,and progression.
Along with aerobic exercise resistance training for 2 non-consecutive complications would benefit more from these interventions and should be
days a week, exercising all muscle groups is recommended to improve given the benefit of this intervention. The barriers to Behaviour counsel-
glycemic control, and improve muscle insulin sensitivity. 165Structured ing interventions (BCI) from a physician's perspective are- Focusing on
exercises have been found to reduce significantly (p<0.001) post- medically necessary issues, Lack of time, Inadequate clinician training,
interventional HbA1c levels compared to the control group, which was Low patient demand, and lack of supportive resources.183
independent of body weight.166 In the Indian Diabetes Prevention Sleep, stress and diabetes
Program report, lifestyle modification that included a minimum of 30 Sleep disturbances lead to impairments in metabolism, increases insulin resis-
min/day of physical labor, exercise, or brisk walking showed significant tance and appetite, and it is recommended that adequate sleep (recommended
relative risk reductions for T2DM either alone (28.5%; p=0.018) or in sleep is 7-8 hours of sleep for adults) contributes to improvement in glycemic
combination with metformin (28.2%; p=0.022) versus the control group. control in diabetes. Chronic stress can modulate the glycemic response through
65
In a cross-sectional comparative study, South Asians were found to various mechanisms including the HPA axis and may have a contributary role
need an additional 10-15 min/day of moderate-intensity physical activity as risk, and glycemic control of Diabetes Mellitus Type 2.184–186
more than the prescribed 150 min/week to achieve the same cardio-
metabolic benefits as the European adults.167 Resistance training, either TREATMENT 1: ORAL HYPOGLYCEMIC AGENTS
alone or in combination with aerobic exercises or walking, has also
shown to significantly improve risk factors of T2DM such as waist cir- Recommendations
cumference, abdominal adiposity, HDL levels, etc.168–170 Based on all
available evidence, the ADA and IDF recommend a total of at least Recommended Care
150 min of moderate-intensity physical activity per week, which can be
a combination of aerobic activities (such as walking or jogging) or resis- General Principles
tance training.171 For Asian Indians predisposed to develop T2DM or CV • Metformin can be initiated in combination with lifestyle interventions at the time of
diagnosis.
risks, an additional 60 min of physical activity each day is recommended,
• Other options: sulfonylurea (or glinides), TZD, dipeptidyl peptidase-4 (DPP-4)
although there is limited data to support this recommendation.172 inhibitors, SGLT2 inhibitors, AGIs or oral GLP1-RA can be used initially for cases
where metformin is contraindicated or not tolerated.
Behavioral lifestyle intervention (BLI) / Behavioral Counseling (BC) • Maintain support for lifestyle measures throughout.
BLI involves patient counseling for strategies such as tailoring goals, self- • Consider each initiation or dose increase of OADs as a trial, monitoring the
response through glucose monitoring (FPG, PPG, self-monitoring of blood glucose
monitoring, stimulus control, etc., that would help motivate patients to inte- [SMBG] or HbA1c) every 2-3 months.
grate the lifestyle management measures into their day-to-day life and identify • Consider CV/heart failure risk, renal/hepatic (NASH) risk and other comorbidities
and manage potential lapses.173 BLI approaches have been shown to improve while deciding therapy.
adherence to lifestyle changes and achieve more sustained effects.174 In pa- • Patient-centric approach: consider cost and benefit risk ratio when choosing OADs.
tients with T2DM, implementation of a six-month BLI program was reported • Customize therapy focusing on individualized target HbA1c for each patient based
on: age, duration of diabetes, comorbidities, cost of therapy, hypoglycemia risk,
to significantly reduce HbA1c levels from baseline at three months (–1.56 ± weight gain, durability.
1.81, p<0.05) and six months (−1.17±2.11, p<0.05). The BLI used cognitive • Consider initiating combination therapy if the HbA1c >1.5 above the target.
behavior therapy that mainly involved monitoring carbohydrate intake (using • Metformin should be initiated in combination with lifestyle interventions at the time
diet charts) and setting targets for weight loss and physical activity across8 of diagnosis unless contra-indicated or not tolerated.
• If eGFR is between 45-30 mL/min/1.73m2: reduce dose of metformin by 50% if
sessions (4 face-to-face and four telephone sessions) administered by clinical
already on metformin and avoid starting metformin therapy if not on metformin;
dietitians.175 BLI using a smartphone or paper-based self-monitoring of pa- stop metformin if eGFR <30 mL/min/1.73m2. Closely monitor renal function every
tient behaviors on weight loss and glycemic control (based on Look AHEAD 3 months.
study) in overweight or obese adults with T2DM showed significant improve- • In some cases, dual therapy may be indicated initially if it is considered unlikely that
ments in HbA1c (p=0.01) at six months and significant weight loss that was single agent therapy will achieve glucose targets or to extend the time to treatment
failure.
not significant.176 A systematic review of randomized studies evaluating • Dualtherapy: Patient-centric approach
lifestyle-based interventions for T2DM found that robust behavioral strategies • If glucose control targets are not achieved: Add (SGLT2) inhibitor, or DPP-4
were essential for successfully implementing such prevention programs. This inhibitor or sulfonylurea or thiazolidinediones (TZDs) or sodium-glucose
study reviewed the Indian Diabetes Prevention Programme that included cotransporter 2 inhibitors, AGI or oral GLP1-RA.
individual patient counseling and diet and exercise goal-setting.177,178 • Individualize patient care based on comorbidities.
• Triple/Quadruple therapy: Patient-centric approach
Behavior Counselling approaches are practical in many studies.179 The • If glucose targets are not achieved with two agents: start third oral agent-AGI, DPP-
regional and cultural differences in the type of diet (especially in India) 4 inhibitor, SGLT2 inhibitor, or TZDs or oral GLP1RA (depending on the second-
and subsequently incidence of prediabetes and diabetes are significant, so line agent used).
lifestyle management, especially nutrition, cannot be generalized or one • Exceptionally, if target HbA1c is not achieved with 3 oral drugs, addition of a fourth
agent with complimentary mode of action to the current OHAs may be considered for
size fits all.Inadequate compliance to lifestyle modifications and medica-
glycemic control.
tions impacts glycemic control. Compliance with drug is also insufficient • In the presence of severe IR, addition of TZDs may be considered along with
(50-60%) 180,181 Diabetes education (HE) has been an integral part of Metformin if not contraindicated.
diabetes management. However, most patients may be unable to make • For patients with established or having high risk for atherosclerotic
a sustainable change by HE alone. BCI or health coaching has been found cardiovascular disease (ASCVD), heart failure, diabetic kidney disease (DKD)
to have a more significant impact than health education for glycemic or in need of weight reduction consider using SGLT2 inhibitors or oral GLP1
Agonists.
control.182 BCI can be done on constructs of various Behaviour change
• For postprandial hyperglycemia, AGI, glinides or SGLT2 inhibitors may be
theories using techniques like the 5 A’s or brief Motivational considered if not contraindicated.
interviewing, which have proved effective. These can be done for indi- • In elderly patients with increased risk of hypoglycemia, use a DPP-4 inhibitor as an
viduals or groups. BCI can be facilitated in brief by the clinician who has alternative to sulfonylurea.
received short ten-hour training or by a trained professional. While all
patients would benefit from BCI, patients with poor glycemic control and
Limited Care Rationale and Evidence
• The principles are same as for recommended care along with considerations for Table 4: Oral antidiabetic agents
cost and availability of generic therapies. In resource constrained situations,
sulfonylurea or metformin or TZDs may be used.
Oral
• Newer sulfonylureas have benefit of low cost and reduced hypoglycemia (than older α-
SGLT- GLP-1 Thiazolidin
OADs); comparable CV safety with DPP4i may be considered. TZDs have DPP-4 glucos
Bigua 2 Analogu Sulphony Meglitin ediones
established CV safety and may be considered as add on to metformin. Inhibit idase
nides Inhibito es lureas ides (Pioglitazo
ors inhibi
rs (Semagl ne)
tors
utide)
Background Expecte
1.0- 0.5-
d 0.8-1.2 1.0-1.5 1.0-2.5 0.5-1.0 0.5-1.0 0.5-0.8
T2DM occurs due to a complex interaction between genetic inheritance and HbA1c
2.0 0.8
multiple risk factors such as obesity and sedentary lifestyle etc.187Relative Conserv
Insulin deficiency and/or Insulin resistance, incretin deficiency/resistance, e β cell No No Yes No No Yes No No
upregulated lipolysis, increased glucose reabsorption from kidney, along with function
Hypogly
downregulated glucose uptake, neurotransmitter dysfunction, increased he- caemia
Very Very
Low High Moderat Very low Low
Very
patic glucose production, and glucagon secretion are the reported metabolic low low low
risk e
derailments that contribute to hyperglycemia in T2DM [Figure].188Among Effects
Weight Weight Weight Weight Neutra
Indians, high familial aggregation, rapid decline in beta cell function, central on body NEUTR Weight gain Neutral
AL
loss loss gain gain l
weight
obesity, insulin resistance, and life style changes due to rapid urbanization are Other GI UTI, Nausea, Oedema
the primary causes of T2DM.189 Greater degree of insulin resistance paired side sympt
GENITAL
FUNGAL Higher HYPOGLYC HYPOGLY
None
GI
with higher central adiposity compared to Caucasians is a characteristic fea- effects oms INFECTIO
NS
rates of EMIA CEMIA SYMP
TOMS
ture of T2DM in Asian Indians.190,191 retinopat
hy
Treatment options for T2DM have been developed in parallel to the in- Increase
creased understanding of underlying pathophysiological defects in T2DM. d lower
A patient-centric and evidence-based approach that may take into account extremit Skin,
y immune
all the metabolic derailments accompanying T2DM, is now gaining impe- Other Lactic
amputat GI side
Heart
safety acidos None None failure, disorder None
tus. Therefore, treatments that target factors beyond glycemic control, such ion with effects s?
issues is fractures
as cardiovascular risks, weight management, along with improvements in canaglif ARTHRI
quality of life have been introduced. 192 Several guidelines/ lozin; TIS
ketoacid
recommendations provide treatment algorithms on ways in which glucose osis
- lowering agents can be used either alone or in combination. No data
Ideally, treatment decisions should be directed based on glycemic effica- Major
( ed
HF
cy and safety profiles, along with impact on weight and hypoglycemia cardiova
CV CV CV Neutral CV hospital CV
risk, comorbidities, route of administration, patient preference, as well as scular Neutral Neutral
events events events events isation events
event/de
treatment costs.193Here the guideline is based on clinical evidences and ath
for
provides overview on available OADs. The treatment algorithms in this saxagli
ptin)
chapter attempt to provide practical recommendations for optimal man- ed for
agement of T2DM in Asian Indians. saxagli
ptin,
Heart
aloglipt Neutra
Considerations failure ed ed Neutral Neutral Neutral ed
in; l
The decision on choice of OAD therapy in T2DM patients is based on the risk
neutral
cost, safety, efficacy and comorbidities that were reviewed in Asian for
Indian context. others
Renal
None +++ ++ None None None None None
benefits
Benefit Not
on None ++ enough None None +++ None None
NAFLD data
Upper Very Low/Hi Mediu
Cost Low Low Low Low
low high gh m
++
Overall ++++ +++ +++ (depends ++ ++ ++ ++
on salt)
Biguanides
Metformin remains the first choice in the management of patients with
T2DM where certain new drugs can be used as first line in selected
patients.194Metformin is efficacious in managing hyperglycemia, increas-
ing insulin sensitivity, along with beneficial effects in reducing cardio-
vascular and hypoglycemia risk, improving macrovascular outcomes, and
lowering mortality rates in T2DM.195Metformin is a complex drug that
exerts its action via multiple sites and several molecular mechanisms.
Metformin is known to down regulate the hepatic glucose production,
act on the gut to increase glucose utilization, enhance insulin, increase
GLP-1 and alter the microbiome.196The UK Prospective Diabetes Study
(UKPDS) Group study in over weight T2DM patients suggested that
intensive glucose control that(with) metformin lowered the risk of
diabetes-related endpoints, diabetes - related deaths, and all-cause
mortality in overweight T2DM patients, compared to insulin and macrovascular events along with improvements in HbA1c, triglycerides,
sulphonylureas.197 A 10-year follow-up study of the UKPDS reported LDL, and HDL levels. However, rate of heart failure was
continued benefit following intensive glucose control with metformin in increased.212TZDs have demonstrated beneficial effects in attenuating
terms of reduced diabetes-related endpoints, diabetes - related deaths, and dyslipidemia commonly observed in patients with chronic T2DM.
all-cause mortality.198 Along with substantial improvements in hypergly- Furthermore, the IRIS trial was among the 1st studies to document the
cemia, metformin improved endothelial dysfunction, oxidative stress, in- CV benefits of TZDs in non-diabetic individuals. Pioglitazone improved
sulin resistance, lipid profiles, and fat redistribution.199 Owing to the CV outcomes (recurrent stroke and MI) and prevented the development
concerns of lactic acidosis and gastrointestinal effects (nausea, vomiting, of T2DM in insulin-resistant, non-diabetic patients with cerebrovascular
diarrhoea and flatulence) metformin should be used cautiously in patients disease.213 In a recent post hoc study of the IRIS trial, conducted in
with renal insufficiency or elderly patients. In patients with an eGFR <60 prediabetic population, pioglitazone effectively lowered the risk of stroke,
mL/ min/1.73 m2 metformin can be used, but should not be initiated in MI, acute coronary syndrome, and hospitalization for heart
patients with an eGFR of 30 to 45 mL/min/1.73m2 and must be contra- failure.214Pioglitazone has been found to have an additional benefit of
indicated in patients with an eGFR below 30ml/min/1.73m2. Long term significantly alleviating NASH in patients with prediabetes or Type 2
Use(>5yrs) of Metformin is associated with vitamin B12 deficiency and Diabetes Mellitus combined with NAFLD. Pioglitazone had been linked
worsening of neuropathy. So, the periodic measurement of vitamin B12 with a possible increased risk of bladder cancer, possibly in a dose-and
level is suggested. time-dependent manner.215 However data from a retrospective study in
India involving 2222 (pioglitazone users, n = 1111; pioglitazone non-
Sulfonylureas users, n= 1111) T2DM patients found no evidence of bladder cancer in
Sulfonylureas can be used as second line agents in patients with T2DM any of the groups, including patients with age >60 years, duration of
patients who are not obese. Sulfonylureas are insulin secretagogues that diabetes >10 years, and uncontrolled diabetes.216 Recognized side effects
act on the ATP-sensitive K+ channels on the β cells and stimulate en- of TZDs include weight gain (3–5 kg), fluid retention leading to oedema,
dogenous insulin secretion.200 As a single therapy, sulfonylureas are ef- and/or heart failure in predisposed individuals and patients with increased
ficacious in lowering fasting plasma glucose and HbA1c. However, con- risk of bone fractures.209,212,216
cerns of modest weight gain and moderate to severe hypoglycemia and
cardiovascular risk limit their clinical benefits.201As a consequence of Dipeptidyl peptidase-IV inhibitors
closure of cardiac K channel, the use of sulfonylureas (Eg: Vildagliptin, saxagliptin, alogliptin, evogliptin sitagliptin, teneligliptin,
Glibenclamide) have also been related to adverse CV effects due to im- and linagliptin are incretin enhancers; they enhance circulating concen-
paired hypoxic coronary vasodilation during increased oxygen demands trations of active GLP-1 and gastric intestinal polypeptide (GIP).217
such as acute myocardial ischemia.202The use of glibenclamide was as- These incretins stimulate insulin secretion, suppress glucagon synthesis,
sociated with an increased risk of in-hospital mortality in patients with lower hepatic gluconeogenesis, and slow gastric emptying. Their major
diabetes and acute myocardial infarction.203 Adverse cardiovascular out- effect is the regulation of insulin and glucagon secretion; they are weight
comes with sulfonylureas in some observational studies have raised con- neutral.218 DPP-4 inhibitors are efficient in improving glycaemia both as
cerns, although findings from recent meta-analysis that included several monotherapy and as add-on to metformin, sulfonylurea and TZDs in
RCTs reported that sulfonylureas when added to metformin were not patients with inadequate glycemic control. A reduction in HbA1c levels
associated with all- cause mortality and CV mortality.204 New generation from baseline of 8.1% was observed with sitagliptin monotherapy (100
sulfonylureas have demonstrated superior safety, mainly due to reducing mg: -0.5%, 200 mg:- 0.6%) in 521 patients treated for 18 weeks.
hypoglycemia, and improved cardiac profile. Sulfonylureas particularly Additionally, homeostasis model assessment of beta cell function index,
gliclazide modified release (MR) and glimepiride have a lower risk of fasting proinsulin-insulin ratio which are the markers of insulin secretion,
hypoglycemia and are preferred in south Asian T2DM patients.205 and beta cell function were also improved significantly.219 The overall
Caution must be exercised while prescribing sulfonylureas for patients incidence of adverse events with sitagliptin is comparable to other OADs
at a high risk of hypoglycemia, older patients and patients with CKD.206 when used as monotherapy or as add-on to existing OADs.220 Adverse
Shorter-acting secretagogues, the meglitinides (or glinides), also stimu- effects (AEs) such as constipation, nasopharyngitis, urinary tract infec-
late insulin release through similar mechanisms and may be associated tion, myalgia, arthralgia, headache, and dizziness are the commonly re-
with comparatively less hypoglycemia but they require more frequent ported AEs with the use of these agents.221 Cardiovascular outcomes trial
dosing. Moreover, modern sulfonylureas exhibit more reductions of (CVOT) studies with DPP-4 inhibitors have shown that these agents are
HbA1c than glinides.207 safe in patients with established CVD and those at increased risk of CVD
except for increased risk of heart failure risk.222TECOS Trial had proven
Thiazolidinediones CV safety for sitagliptin and no additional excess hospitalization for heart
Drugs from this class are peroxisome proliferator activated receptor γ failure.223Results of the SAVOR-TIMI study and EXAMINE Study have
activators that improve insulin sensitivity by increasing insulin- reported higher rates of hospitalization for heart failure with saxagliptin
mediated glucose uptake in skeletal muscle, suppressing hepatic glucose and alogliptin, respectively.224,225Owing to the increased risk of hospital-
output, and improving the secretory response of insulin in pancreatic β- ization due to heart failure in patients with cardiovascular disease, the US
cells.208] The risk of hypoglycemia is negligible and TZDs may be more FDA issued a warning, suggesting the associated risk to be a “class-
durable in their effectiveness than sulfonylureas.209 TZDs have been con- effect” of the DPP-4 inhibitors and issued a warning for their use.226
stantly under the authority scrutiny for their cardiovascular safety. A However, some landmark studies have been conducted to evaluate rela-
meta-analysis considering data from 42 trials and 27,847 patients indicat- tionship between these drugs and the adverse effects. In the
ed that treatment with rosiglitazone was associated with an increase in the CARMELINA study, linagliptin demonstrated a long-term CV safety
odds of MI (odds ratio 1.43, 95% CI 1.03 to 1.98, p=0.03) and a nonsig- profile in patients with T2D, including those with CV and/or kidney
nificant increase in the odds of cardiovascular death (odds ratio 1.64, 95% disease and no increased risk of hospitalization for heart failure versus
CI 0.98: 2.74, p=0.06) compared with a control group (active comparator placebo was reported.227The CAROLINA study was designed to evaluate
or placebo).210Pioglitazone is known to exert pleotropic effects on car- the long-term CV safety profile of linagliptin versus glimepiride in pa-
diovascular event; pioglitazone improves endothelial dysfunction, lowers tients with early T2D at increased CV risk. The study results highlight a
hypertension, improves dyslipidemia, and lowers circulating levels of non-inferiority between linagliptin versus glimepiride in time to first oc-
inflammatory cytokines and prothrombotic factors.211 In the PROactive currence of CV death, non-fatal MI, or non-fatal stroke (3P-MACE) with
study, pioglitazone lowered the composite of all-cause mortality, non- a median follow-up of more than 6 years.228
fatal myocardial infarction, and stroke in T2DM patients with at risk of
Sodium-glucose co-transporter 2 inhibitors to-head trials, any differential effects on glucose control between different
They provide insulin-independent glucose-lowering by blocking glucose OADs are small. So, agent and patient-specific properties, such as ease of
reabsorption in the proximal renal tubule. The capacity of tubular cells to administration, dosing frequency, side effect profiles, cost, and other
reabsorb glucose is reduced by SGLT2 inhibitors leading to increased benefits, often help in their selection.
urinary glucose excretion and consequently, correction of the
hyperglycaemia.229 Dapagliflozin, canagliflozin, empagliflozin, and Oral Glucagon Like Peptide1 Receptor Agonist
remogliflozin are the 4 Drug Controller General of India (DCGI) ap- Oral semaglutide is world’s first oral GLP-1RA approved for the man-
proved agents used in patients with T2DM.230,231In The EMPA-REG agement of Type 2 diabetes in adult population. Oral Semaglutide is the
OUTCOME trial, patients with Type2 diabetes with high risk of cardio- latest addition to the oral antidiabetic agents. The development of this
vascular events and estimated glomerular filtration rate (eGFR) of at least drug is the result of significant innovation in the oral drug delivery with
30 mL/min/1.73 m2, who received empagliflozin, as compared with pla- the use of absorption enhancer. It has significant HbA1c lowering effica-
cebo, had significantly lower rate of the primary composite cardiovascu- cy along with significant weight reduction. It is safe for mild to moderate
lar outcomes and all-cause mortality. Empagliflozin reduced the rate of renal impairment. This drug will play an important role in the manage-
new onset or worsening nephropathy, which were defined as new-onset ment of Type2 diabetes with obesity for those preferring oral therapy.
microalbuminuria, doubling of creatinine, and eGFR ≤45 mL/min/1.73 Oral semaglutide has undergone a clinical trial program named as
m2, initiation of renal replacement therapy, and death due to renal disease PIONEER trials. Oral semaglutide showed significant HbA1c and weight
(hazard ratio [HR]: 0.61, 95% CI: 0.53, 0.70; p<0.0001). 232 The reduction in comparison to sitagliptin, empagliflozin and injectable lirag-
CANVAS Program integrated data from two trials involving a total of lutide. Oral semaglutide has shown HbA1c reduction up to 1.5 % and
10,142 participants with type 2 diabetes and high cardiovascular risk. weight reduction up to 5 kg at end of 26 weeks. Approximate 50 % of
Treatment with canagliflozin showed a possible benefit with respect to patients achieved >5 % of weight loss. Oral semaglutide has shown to be
the progression of albuminuria (HR: 0.73; 95% CI: 0.67, 0.79) and the CV safe in PIONEER 6 trial and shown 21% non-significant reduction in
composite outcome of a sustained 40% reduction in the estimated glo- MACE. Oral semaglutide has also shown reduction in CV risk factors like
merular filtration rate, the need for renal- replacement therapy, or death dyslipidemia, systolic blood pressure and hsCRP levels 246–249
from renal causes (HR: 0.60; 95% CI: 0.47, 0.77).233Canagliflozin in Oral semaglutide has safety profile similar to other injectable GLP-1Ras.
combination with metformin significantly improved glycemic control in The most common side effects are gastrointestinal events (nausea,
patients with T2DM and significant weight loss along with low incidence vomiting and diarrhea). These are usually mild to moderate in nature
of hypoglycemia have been reported.234 A recent meta-analysis conclud- and go away with time.
ed that SGLT2 inhibitors, as a class, significantly reduce 24-h ambulatory Oral semaglutide can be used in addition to metformin or as a monother-
blood pressure further substantiating their favorable cardiovascular pro- apy if metformin is contraindicated. Oral semaglutide can be used across
file.235 The most common AEs involving this class are genital mycotic e GFR without any dose adjustment. 246–250The main disadvantage of this
infections, which are believed to be mild and respond favorably to anti- is the cost of the drug.
fungal therapy.236–240
In CREDENCE trial, in the patients with Type 2 diabetes and kidney Miscellaneous Anti-Diabetic Drugs
disease, the risk of kidney failure and cardiovascular events was lower • Hydroxychloroquine HCQ has been approved by DCGI for selected
in the Canagliflozin group compared to the placebo group.241 patients in which blood sugar levels are not controlled with two anti-
In DAPA HF Trial, the patients with heart failure with reduced ejection diabetics.
fraction, those who received Dapagliflozin had a lower risk of worsening • Saroglitazar can be used in diabetic patients with hypertriglyceridemia
heart failure and cardiovascular death.242 and NASH with the additional advantage of mild HbA1c reduction.
• Bromocriptine
Alpha glucosidase inhibitors • Colesevelam
These agents delay the absorption of consumed carbohydrates by com-
petitively inhibiting the α-glucosidase enzymes at the enterocyte brush These drugs have been used as adjuncts with other antidiabetics.
border. This inhibition delays the digestion of starch and sucrose and However, older drugs have typically been tested in clinical trial partici-
maintains levels of postprandial blood glucose excursions.243 The action pants with higher baseline HbA1c, which is associated with greater
of these agents is independent of insulin action and hence are devoid of treatment-emergent glycemic reductions, irrespective of therapy type. In
hypoglycemic adverse effects. In the Essen-II Study, conducted in 96 head-to-head trials, any differential effects on glucose control between
patients, acarbose significantly lowered HbA1c levels when compared different OADs are small. So agent and patient-specific properties, such
with placebo and treatment with acarbose was associated with a weight as ease of administration, dosing frequency, side effect profiles, cost, and
reduction of -0.8 kg.244 When added to background of metformin, treat- other benefits, often help in their selection.
ment with acarbose led to HbA1c reduction of 0.7%.245The AGIs have • Two-drug combination therapies with metformin (such as metformin
demonstrated an acceptable safety profile with major complaints being of plus TZDs, metformin plus sulfonylureas, metformin plus SGLT2 in-
flatulence and diarrhea. hibitors, and metformin plus DPP4 inhibitors, DPP4+ SGLT2) were
The glucose-lowering effectiveness of OADs is said to be high with more effective in reducing HbA1c than metformin monotherapy by
metformin, sulfonylureas, and TZDs (expected HbA1c reduction ~ 1.0– about 1%.251 In addition, triple FDC of metformin and sulfonylurea
1.5%) and comparatively lower for meglitinides, DPP4 inhibitor, SGLT2 plus pioglitazone are also available in India.
inhibitor, AGIs.221 • RSSDI wheel given along with this recommendation book will help
However, older drugs have typically been tested in clinical trial partici- practitioners choose an ideal drug for his patient based on cost, weight,
pants with higher baseline HbA1c, which is associated with greater treat- hypoglycemia risk, and other comorbid conditions.
ment emergent glycemic reductions, irrespective of therapy type. In head-
TREATMENT 2: INJECTABLES insulin-

» Switch to premix insulin twice-daily or premix analogs twice or thrice-daily
» Switch to insulin co-formulation-based regimen
Recommended Care
» Add prandial insulin (basal plus or basal-bolus) with the largest meal of the
» Insulin therapy should be considered in all patients failing to achieve glycemic day
targets on three oral agents. However, additional oral agents can be considered in » Add GLP-1 analogs
subjects with HbA1c 1% to 1.5% above the mark. Clinicians must consider the - The choice of intensification strategy should be based upon dietary pattern,
limitations of individual oral agents or their combinations in terms of the quantum of lifestyle, risk of hypoglycemia and weight gain, affordability, and patient
HbA1c reduction. preference.
• Consider initiating Insulin in type-2 diabetes patients with severe symptomatic - Basal plus regimen can be used as a stepwise approach to insulin intensification,
hyperglycemia or unstable state. leading to basal-bolus prescription. It is associated with a lesser risk of
• A three-step protocol involving initiation, titration, and intensification is hypoglycemia and weight gain than the basal-bolus regimen.
recommended for all patients requiring insulin. - Both premix insulin therapy and co-formulation insulins are acceptable methods
• Initiation of intensification. Co-formulation insulin offers the advantage of lower risk of
hypoglycemia and nocturnal hypoglycemia. This also has the advantage of lesser
- “Providers should avoid using insulin as a threat or describing it as a sign of nocturnal hypoglycemia and lesser insulin dosage than the Basal plus or basal-
personal failure or punishment and should work to alleviate patient’s anxiety bolus regimen.
about hypoglycemia, dependence, injection-site pain, etc., commonly attributed - Follow insulin intensification as recommended in the algorithm.
to insulin.”
- Therapeutic choice of regimen, preparation, and the delivery device should be
made through shared, informed decision making.
• GLP-1 analogs
- Initiate with once-daily basal insulin, once-daily premixed/co-formulation
- GLP-1 analogs with proven CV benefits should be considered to reduce the risk.
insulin, or twice-daily premixed insulin, either alone or in combination with
other OADs, based upon patient’s age, clinical features, glucose profile, risk of - Viable second-line or third-line options for managing patients with uncontrolled
hypoglycemia, and patient preference. Basal insulin may also be initiated in hyperglycemia.
combination with GLP-1 analogs. - Can be considered in overweight/obese patients as second-line therapy in
- Basal bolus insulin regimens may be needed in severe hyperglycemia, and life- patients with metformin inadequacy and first-line therapy in patients with
threatening or organ/limb threatening clinical situations. metformin intolerance.
- Analogue insulins may be used in preference to human insulins with a possible To be added to insulin therapy, preferably basal insulin only if glycemia goals are not
lower risk of nocturnal and symptomatic hypoglycemia; however, economic achieved with reasonably high dose insulin doses if unacceptable weight gain or
considerations must be taken into account. hypoglycemia occurs. Dose reduction of insulin may be needed in such cases. Transient
gastrointestinal side effects may occur.
- Meal timing should match with insulin dose.
- Counselling/education about SMBG, hypoglycemia prevention/recognition, and
treatment are recommended for all patients initiating insulin.
- Guidance adjusting insulin dose adjustments, administration, storage, and other Limited Care
practical aspects should be made available.
• All conventional insulins have similar glycemic lowering efficacy as analogs but
• Titration with a slightly increased risk of hypoglycemia and lack of administration
- Initiate insulin as defined in the algorithm, using a self-titration regimen (dose flexibility.
increases of 2–4 Units (U) weekly or biweekly) or with more frequent contact • Insulin supplies should be assured and be of consistent quality and type.
with a healthcare professional.
- Aim for pre-meal glucose levels of <115 mg/dL and PPG levels of <160 mg/dL.
These targets can be individualized based on the risk of hypoglycemia and the Background
urgency for glycemic control. Subjects with an increased risk of hypoglycemia
<130 mg/dl and <180 mg/dl should be optimum.
Most treatments available to control glycemia impact the pathways targeting
- Titration should be done to control FBG first, followed by prandial control.
β-cells or insulin resistance (IR). Their efficacy depends upon the presence of
However, if premixed or co-formulation is used, then FBG and pre-dinner insulin for their therapeutic effect. The durability of these medications varies,
glucose can be targeted simultaneously. Meal with highest glycemic excursion in and their safety is occasionally under scrutiny. Over a period, patients fail to
sequential order. achieve or maintain HbA1c levels even with multiple OADs and will require
• Intensification insulin therapy. Although insulin is the most effective option for glycemic
- Intensification of insulin therapy is recommended when patients fail to achieve
control, it should not be used as a first-line treatment in T2DM, as it can
glycemic goals even after optimal dose titration.
- Several options can be considered during intensification. In patients on basal
predispose to hypoglycemia, weight gain, and large doses over prolonged
duration might increase the risk of malignancy and cardiovascular diseases.
However, it is equally essential to ensure timely initiation of insulin without
delay once optimal combinations of oral hypoglycemic drugs have failed to
achieve the target HbA1c.
Most guidelines recommend early short-term insulin therapy in patients with
high HbA1c at the time of presentation in subjects with catabolic symp-
toms.252–254 Landmark trials in the last decade suggest that glycemic control
should be intensive in the early stages of diabetes, preferably in the first four
years of diagnosis, to create an excellent metabolic memory.197,255,256The
traditional postponement of insulin therapy up to the prolonged failure of
lifestyle and oral agents to achieve glycemic control has been revised in the
last decade to incorporate insulin therapy much earlier, often in combination
with OADs or GLP-1 analogs to reduce long term micro vascular and macro
vascular complications. Non-insulin injectables such as GLP-1 and amylin
analogs (pramlintide) have been approved in various countries. The GLP-1
analogs improve glycemic control through multiple mechanisms, have a low
risk of hypoglycemia, and provide clinically relevant weight loss.257 As
pramlintide is unavailable in India, these recommendations will not cover it.
Consideration Table 5: Clinical situations where the use of injectables is recommended

The decision on injectable therapy in T2DM patients is based on clinical,
pharmacological, and psychosocial factors. Additionally, local factors Short term insulin GLP-1analogss Basal insulin
such as cost, quality, cold chain maintenance, and perennial availability + GLP-1
of insulin preparations and delivery devices must be considered in the Catabolic symptoms Recommended as Recommen
Indian context. High glycemic parameters: HbA1c >9.0%, the first injectable ded in cases
As suggested above, if optimal doses of three or more (in selected subjects) FPG >200 and/or PPG >300 mg/dL Acute option in subjects where
diabetic complications/medical conditions failing on further
oral antidiabetic agents for 3–6 months fail to achieve HbA1c targets or organ optimum intensificati
Hospitalized patients not suitable for OADs:
dysfunction contraindicates the use of oral agents, the addition of insulin may Perioperative, transplants, critical care units combination of on of
be justified. The landmark studies support this idea and suggest that gaining Pregnancy oral drugs therapy is
intensive Glycemic control (if not contraindicated) is profoundly beneficial in (standard care): required
Concomitant
the initial few years of diagnosis.
CVD, CKD,
Insulin may be started with two oral drugs, which have the advantage of Where
weight reduction, no hypoglycemia, and cardio-renal benefits. However, hypoglycemia
in the majority, Insulin should be used with metformin if the latter is not and weight gain
contraindicated and is well tolerated. As the patient’s glucose toxicity must be avoided
resolves, the regimen can potentially be de-escalated, and a switch over CKD: Chronic kidney disease, CV: Cardiovascular, CVD: CV disease, HbA1c:
to oral therapy may be considered. Glycosylated hemoglobin, OADs: oral antidiabetics, FPG: Fasting plasma
glucose, GLP-1: Glucagon-like peptide 1, PPG: Postprandial glucose
HbA1c targets must be determined as criteria set for individualized ther-
apy efficacy of each agent as combination therapy must be
considered.258The near-normal glycemic target of 6.5% should be con- Adverse events and barriers
sidered for younger patients with recent onset of T2DM with few or no Hypoglycemia is a significant safety concern with insulin treatment and can
micro or macrovascular complications. In comparison, slightly higher be a barrier to initiation or intensification.260Addition of Sulphonylurea and
HbA1c targets may be considered for older patients with long-standing TZDs can accentuate the risk of weight gain with insulin treatment 261.
T2DM and evidence of CVD, organ failure, and terminal illnesses.259 However, addition of SGLT 2 inhibitors and Oral or injectable GLP-1 RA
While initiating insulin, doses of OADs should be modified as follows: are likely to mitigate the weight gain caused by Insulin. Combination with
DPP4 inhibitors results in weight neutrality, and combination with metformin
- No change in metformin doses, DPP4i, SGLT 2 inhibitors, AGI and TZDs. or AGIs in combination may produce weight loss compared with insulin
- Dose of sulphonylureas should be reduced when prandial insulin is monotherapy.262
introduced. Insulin use is hindered by a variety of social barriers. A recent National
- Risk of unacceptable weight gain should be kept in mind while prescribing Insulin Summit (NIS) consensus lists the barriers to insulin therapy related
insulin with TZDs and the latter should be withdrawn if such weight gain is to patient/community, physician/provider, and drug/device and proposes dif-
seen. ferent bridges to overcome these hurdles. Patient-related barriers such as the
inability to inject, monitor, or titrate the insulin dose, weight gain, hypogly-
(Adequate doses of oral agents do not necessarily mean the highest ad- cemia, and lack of awareness of uncontrolled diabetes can be bridged with
ministrable doses because, in most cases, doubling the doses of these patient education and training, support and counselling and social marketing.
medicines does not necessarily increment their effects.) Physician and provider barriers such as inadequate communication or moti-
vation skills, inability to initiate, optimize or intensify insulin, and lack of
Rationale and Evidence awareness may be addressed through relevant skill development training and
continuing medical education (CME). Furthermore, drug or device-specific
The insulin strategy barriers such as suboptimal effects of insulin, lack of flexibility, and device
While initiating the insulin therapy, the following features have to be discomfort can be surmounted through CME, flexible insulin regimens and
considered; choosing the appropriate regimen, identifying the proper preparations and modern devices.263
preparation, prescribing the available strength of the molecule, matching
it with the correct delivery device, deciding the proper insulin dose, and Initiation of insulin therapy
following the optimal titration strategy. Premixed/co-formulation or basal insulin are usually initiated as initial
Ideally, an insulin treatment program should be designed specifically for the therapy unless the patient is experiencing a medical, surgical, or obstetric
individual patient, matching the insulin supply to his/her dietary/exercise crisis or metabolic decompensation.194,252,254,264 General concept is to
habits and prevailing glucose trends as revealed through self-monitoring. first correct the fasting hyperglycemia with a dinner/bedtime injection
Anticipated glucose-lowering effects should be balanced with the conve- and then address postprandial hyperglycemia. However, IDeg Asp (co-
nience of the regimen in the context of an individual’s specific therapy goals. formulation) is to be used preferably before the largest meal of the day.
Patient Education Choice of initial insulin is often dictated by subjective features such as
Proper patient education regarding monitoring of glucose, insulin injec- disease severity and the patient's ability to self-inject at specific times of
tion technique, insulin storage, recognition/treatment of hypoglycemia the day [Table 4]. Even though FPG and PPG measurements provide
and sick day management is imperative. Diabetes educators, where avail- sufficient information to choose an insulin type, it is difficult to make
able, are invaluable in guiding patients through their treatment. an appropriate decision when they are considered separately. Similarly,
the choice of insulin based on the HbA1c value alone can be challeng-
ing.265 All international and Indian guidelines recommend insulin initia-
tion with basal or premixed/co-formulation insulins except ADA/EASD
and AACE guidelines which prefer basal insulin for initiation.
Intensification of Insulin therapy (Tables # and ##)

Most patients with T2DM requiring insulin therapy can be successfully treat-
ed with one or two doses; a few may require a third dose of premix insulin or
a basal plus followed by bolus therapy requiring three to four doses.
Table 6: Choice of insulin therapy
Basal insulin Premixed/co-formulation Prandial insulin

OD or BID
HumanNPH; Human premixed (30/70 Human regular;
glargine U100; or 50/50); BiAsp 30/70; Lispro Aspart;
glargine U300; LisproMix 25/75; glulisine; FiASP
detemir; degludec IDegAsp 30/70 Inhaled insulin
All have equal efficacy All have equal efficacy To be administered when an
Duration of action: Most patients should be individual fails to achieve
Degludec > glargine initiated with either a co- glycemic targets following
U300 > glargine U100 > formulation or premixed basal insulin
detemir > NPH 30/70 or 25/75. HbA1c above target with ~0.5
NPH, detemir, and In subjects with uncontrolled U/kg/day of daily basal insulin
glargine U100 may need PPG-premixed 50/50 can be Elevated HbA1c despite
to be given twice daily used before the meal normal FPG (in the absence
High doses of glargine showing highest excursion of available PPG readings)
U100 beyond 0.5 U/kg Starting dose: 10 U OD or with basal insulin
body weight should be 6 U BID followed by FPG with basal insulin is
split to avoid weekly or biweekly within the targeted range, but
hypoglycemia titration PPG is persistently above the
Starting dose: 10 U of IDegAsp does not produce goal. Further increase in basal
basal insulin followed shoulder effect 4-6 h post- insulin results in
by weekly or biweekly injection as observed with hypoglycemia
titration BiAsp 30/70 or LisproMix
Degludec and glargine 25/75
U300 cause the least IDegAsp causes the least
hypoglycemia with no hypoglycaemia requires
tailing effect of fewer dose, and causes
hyperglycemia the least weight gain
Glargine U300 IDegAsp has the
requires 20% extra flexibility of
doses, but a lesser administration
volume is required before any large meal of
Glargine U300 can be the day and can be
used where a high given with different meals
volume of insulin is on different days BiAsp Figure 2: Approaches for initiating insulin. 266 OD: Once daily; BID:
required 30/70 and LisproMix Twice daily; TID: Three times a day; GLP-1 RA: Glucagon-like peptide-
25/75 are approved for
Detemir causes the least 1 receptor agonist; IAsp: Insulin Aspart; IDegAsp: Mix of insulin
use in pregnancy
weight gain degludec and insulin aspart; A1c: Glycated hemoglobin; DPP-4i:
Basal insulin should
Dipeptidyl peptidase-4 inhibitors; FPG: Fasting plasma glucose; GLP-1
be given preferably at
bedtime to achieve RA: Glucagon-like peptide-1 receptor agonist; SGLT2i: Sodium-glucose
adequate suppression co-transporter 2 inhibitors; TDD: Total daily dose
of HGP
NPH and detemir are Basal plus regimen requires regular insulin administered about 30 min
approved for use in
pregnancy and
before meals or rapid insulin analogs such as insulin lispro (ILis), insulin
with steroid use aspart (IAsp), or insulin glulisine (IGlu), which can be injected just before
or with the meal. They result in better PPG control than human regular
insulin.
BID: Twice daily, BiAsp: Biphasic insulin aspart, IDegAsp: Mix of insulin degludec and
insulin aspart, NPH: Neutral protamine Hagedorn, OD: Once daily,
Glucagon-like peptide-1 analogs:
HGP: Hepatic glucose production, FPG: Fasting plasma glucose, HbA1c: Glycated The injectable GLP-1 analogs like liraglutide, exenatide, lixisenatide,
hemoglobin, PPG: Postprandial glucose dulaglutide, and albiglutide imitate the effects of Endogenous GLP-1,
stimulate pancreatic insulin secretion in a glucose-dependent fashion,
suppress pancreatic glucagon output, slow gastric emptying, and decrease
appetite. Their main advantage is weight loss, which can be significant in
some patients. The limiting side effects of these agents are nausea and
vomiting, particularly early in the course of treatment.267 In combination
with basal insulin, they have proved to be extremely useful for intensifi-
cation because of additive action (IDegLira, Lixilan). Individual agents in
this class should be initiated and optimized as per recommended
schedules.
There have been concerns regarding an increased risk of pancreatitis with
GLP-1 analogs but recently published
Table 7: Steps for initiating basal insulin
Step 1: Glucose Value TDD

HbA1c <8% 0.1-0.2 U/kg
Step 2: Titration# (every 2‑3 day to reach FPG HbA1c >8% 0.2-0.3 U/kg
target)
Fixed regimen Increase by 2 U/day
Adjustable regimen
FPG >180 mg/dL Add 4 U

FPG 140-180 mg/dL Add 2 U
FPG 110-139 mg/dL Add 1 U
Step 3: Monitor for hypoglycemia BG <70 mg/dL Reduce by 10%-20%
BG <40 mg/dL Reduce by 20%-40%
*Consider decreasing the dose of the SU therapy, and basal analogs should be preferred over NPH
insulin, #For most patients with T2DM taking insulin, glucose goals are HbA1c <7% and fasting and
premeal BG <115 mg/dL in the absence of hypoglycemia. HbA1c and FPG targets may be adjusted
based on the patient's age, duration of diabetes, comorbidities, diabetic complications, and
hypoglycemia risk. DM: Diabetes mellitus, BG: Blood glucose, FPG: Fasting plasma glucose,
HbA1c: Glycosylated hemoglobin, NPH: Neutral protamine Hagedorn, SU: Sulfonylureas, T2DM:
Type 2 DM, TDD:
Table 8: Titration algorithm Figure 3: Steps for initiating premixed insulin. OAD: Oral antidiabetic
agents; GLP-1 RA: Glucagon-like peptide-1 receptor agonist; OD: Once-
Basal insulin Prandial insulin Premixed insulin daily; BID: Twice-daily; TID: Thrice-daily; TZD: Thiazolidinedione;
DPP-4I: Dipeptidyl peptidase-4 inhibitors
Given preferably at Initiate along with meal with Calculate the total dose ELIXA and LEADER studies do not show any increased risk of pancre-
bedtime to achieve highest glycemic excursion Start Start with 6 U BID day for
adequate hepatic with 4 U and increase by 1 U/day
atitis, pancreatic cancer, or thyroid cancer with lixisenatide or
analogs and 2/3 dose in the
glucose production or 3 U/3 days till PPG <180 morning and 1/3 dose in the
liraglutide.268,269
(HGP) suppression, The next meal with the highest evening for human insulins Furthermore, in the LEADER trial, the primary composite outcome of the
Target: FPGL <115 glycemic excursion should be Titration can be done for first occurrence of death from CV causes, non-fatal MI, or non-fatal
mg/dl titrated similarly morning dose based on stroke was significantly less with liraglutide as compared to placebo
Initiate with 10 U at Full basal-bolus can be considered predinner values and for
bedtime and check for effective prandial
(HR, 0.87; 95% CI: 0.78, 0.97; p<0.001 for non-inferiority; p=0.01 for
evening dose based on FBG
FBS control after all meals 1 U/day or 3 U/day to
superiority).269 Based on this result, liraglutide is approved for its CV
Increase dose by 2U achieve the required BG benefits as well by FDA “as an adjunct to standard treatment of CV risk
weekly or biweekly targets factors to reduce the risk of major adverse CV events (CV death, non-fatal
by patient self-
MI, or non-fatal stroke) in adults with T2DM and high CV risk.270
titration till target
FBSL is achieved.
BID: Two times Implementations
daily, BG: Blood A challenging aspect of diabetes care is the timely initiation and intensi-
glucose, FBG:
fication of injectable therapy. This must be addressed by focusing on
Fasting BG, FBSL:
Fasting blood sugar patient education and motivation and updating health care professionals'
level, FPG: Fasting knowledge. Lifestyle modification, self-monitoring, and insulin educa-
plasma glucose, tion should be integral parts of insulin therapy in T2DM. Structured
HGP: Hepatic guidelines and protocols should be shared, and glycemic audits of persons
glucose
on oral medications should be performed to address the issue.
production, PPG:
Postprandial glucose
Table 9: Insulin intensification options Table 10: Steps for intensification of insulin therapy
Insulin regimen Characteristics Therapeutic TDD

option
Basal plus One basal insulin along with one prandial insulin
Step 1: Add prandial insulin When glycaemic TDD 0.3-0.5 U/kg
regimen before the meal shows the most considerable PPG
targets are unmet (40%-50% basal:
excursion Advantages: Flexibility and can be
50%-60% prandial) *
further intensified to cover 2 or 3 meals (complete
basal-bolus regimen) Step 2: Titration# (every 2-3 days Fixed regimen Increase TDD by 2
Disadvantages: Needs two insulins, two pens, and two to reach glycaemic goals) (prandial insulin) U/day
different titrations for individual components bringing in
complexity in the regimen Adjustable regimen
(prandial insulin)
Premixed If used thrice daily, then the afternoon dose should be 4-6 U to
insulins start with, and the morning dose to be reduced by 10%-20% FPG >180 mg/dL Increase TDD by 4 U
BID or
TID FPG 140-180 Increase TDD by 2 U
mg/dL
Co-formulation BID is sufficient and is as effective as the basal-bolus regimen
IDegAsp Can be given before any two large meals of the day so FPG 110-139 Increase TDD by 1U
long as the interval between two injections is six h mg/dL
(corresponding to the time action profile of the aspart
2-h PPG or next Increase prandial dose
component)
premeal glucose for the next meal by
Compared with the Basal plus regimen twice-daily, IDegAsp >180 mg/dL 10%
causes similar efficacy, lesser nocturnal hypoglycemia, and has the
convenience of one insulin and one pen Premixed insulin
Compared with the basal-bolus regimen, IDegAsp causes
identical reductions in HbA1c, lesser hypoglycemia, requires FPG/premeal BG Increase TDD by 10%
lesser doses, more secondary weight gain, and is simple to >180 mg/dL
administer
Step3: Monitor Fasting Reduce basal insulin
Basal bolus Most physiological and most effective regimen for intensification for hypoglycemia dose
regimen hypoglycemia
Requires one or two injections of basal insulin, and three
Night time Reduce basal
injections of prandial insulins
hypoglycemia insulin or reduce
Complex regimen and requires an understanding of different
short/rapid-acting
titration schedules for basal and prandial components. Knowledge
insulin taken
of carbohydrates counting is desirable for proper dosing of
before supper or
prandial component
evening snack
It needs persistent monitoring, which could be painful and
expensive Between meal Reduce previous
hypoglycemia premeal short/rapid-
BID: Twice daily, IDegAsp: Mix of insulin degludec and insulin as part, PPG: Postprandial acting insulin
glucose, TID: Thrice daily, HbA1c: Glycosylated hemoglobin
*Basal + prandial insulin analogs preferred over NPH + regular insulin or premixed
insulin, #For most patients with T2D taking insulin, glucose goals are HbA1c <7%
and fasting and premeal BG <110 mg/dL in the absence of hypoglycemia. HbA1c
and FPG targets may be adjusted based on the patient’s age, duration of diabetes,
presence of comorbidities, diabetic complications, and hypoglycemia risk. BG:
Blood glucose, FPG: Fasting plasma glucose, NPH: Neutral protamine Hagedorn, 2-
h PPG: 2-h postprandial glucose, TDD: Total daily dose, FPG: Fasting plasma
glucose, T2D: Type 2 diabetes,
HbA1c: Glycosylated hemoglobin
INDIVIDUALIZING THERAPIES AND PRECISION weight gain compared to NPH or Premix insulins.282,283 Moreover a
DIABETOLOGY pooled analysis from RCTs revealed that addition of modern insulin
analogues to oral antidiabetic drugs in older adults was effective with
ABCD (EFGH) approach for diabetes management Choice of regards to lower risk of hypoglycemia compared to NPH insulin.284
any OAD agent should consider the patient’s general health status • Individualization of therapy is highly desirable based on risk of hypo-
and associated medical disorders. This patient-centric approach glycemia, comorbidities, functionality, cost, and personal preference in
may be referred to as the ABCD (EFGH) approach for diabetes elderly people with diabetes.
management. For any T2DM patients, the first line of therapy
should be metformin unless it is not tolerated by the patient or Body mass index
contraindicated. • While prescribing pharmacological treatments for overweight or obese
patients with T2DM, one should first consider anti-diabetic medications
Individualized treatment which cause either weight loss or weight neutrality. GLP- 1 RA and
• For patients diagnosed with diabetes, consider a combination of metfor- SGLT2i are associated with weight loss. DPP-4 inhibitors and AGIs
min and one of the treatment options based on patient’s age, BMI, CKD, appear to be weight neutral while Glitazones, Sus, and insulin can lead
duration of diabetes, established CVD, financial condition, glycemic to weight gain.285,286 A systematic review and meta-analysis of 62
status, and hypoglycemia risk. randomized trials revealed that, when compared to other antidiabetic
• Drug choice should be based on patient preference, presence or absence agents, SGLT2i and GLP-1 RA were associated with clinically signif-
of various comorbidities and complications, and drug characteristics to icant body weight loss (range, 1.2–2.3 kg) as add-on to metformin.287
reduce glucose levels while minimizing side effects, especially hypo- • GLP-1 RA and/or SGLT2i seem to be the best add on therapy for those
glycemia and weight gain. having high BMI. These groups of medications has highest weight
• A comparative effectiveness meta-analysis suggests that most available reducing property in addition to excellent efficacy. A recent systematic
non-insulin agents added to metformin therapy lower HbA1c around review and meta-analysis reported that GLP-1 RA are associated with
0.9-1.1%271. In contrast, all oral antidiabetic agents and GLP-1 RA can weight loss (–1.62 kg to –1.01 kg) in overweight or obese patients with
reduce HbA1c by 0.5–2.0% insulin can reduce HbA1c even up to 3.5% T2DM with no difference in weight loss between different types of
when used as monotherapy.272 GLP-1 RA.288
• SGLT2i also has a weight reduction property. Evidence suggests
Age that SGLT2i were associated with weight loss in patients with
• DPP-4 inhibitors may be a suitable addition to metformin for elderly T2DM.289,290 Agents of this class have an additional advantage
patients (≥ 65 years) as there is very low risk of hypoglycemia and that they can be given orally. However, a careful consideration
weight gain; however, the dosage should be adjusted as per eGFR.273 should be given to possible taken with regards to known side
Recent RCTs have reported that gliptins are efficacious and safe with effects such as recurrent genital infections, postural hypotension,
minimal side effects when used as add-on therapy in elderly patients and dehydration.
with T2DM.274–277 • DPP4 inhibitors are weight neutral and thus can be used as the
• AGIs could also be a good choice for elderly patients. These second or third line of antidiabetic agents. 291,292 As some
agents have modest efficacy (A1c ↓ ~ 0.5%) and do not cause Gliptins like Sitagliptin and Vildagliptin having gone off patent,
hypoglycemia. The major limiting factor for their use is the the prices of these agents have dropped making them more af-
gastrointestinal side-effects, such as flatulence and diarrhoea278. fordable. In addition, DPP4i are shown to be more effective in
A double-blind RCT revealed that the addition of acarbose im- Asians in general and Indians in particular.293,294, 295
proved the glycemic profile and insulin sensitivity in elderly • Agents such as teneligliptin which are used exclusively in India led to
patients with T2DM. AGIs were also proven to be more useful significant and clinically meaningful reductions in HbA1c and PPG in
especially in terms of Glycemic reduction in Asians because of Indian patients with T2DM.296
high carb intake as seen in the mentioned STARCH study as • Use of newer SUs such as gliclazide MR and Glimepiride do not result in
well. 279 significant weight gain in patients with T2DM unlike the older SUs.297–299
• The use of glitazones is restricted in elderly T2DM patients owing to the • Lean patients with T2DM with low-normal body mass index (<18). are
anticipated complications like weight gain, fluid retention, peripheral a distinct group of patients which are common in India. These patients
oedema, lens-oedema, aggravation of congestive heart failure, and os- are usually younger age at onset, lower insulin reserve and hence have
teoporosis in post-menopausal women. Newer SUs like extended- greater need for insulin.300
release formulations of low doses of Gliclazide and low-dose
glimepiride due to their low risk of hypoglycemia can be safely used In those with diabetic kidney disease (CKD)
in elderly patients with T2DM.280,281 In patients with renal impairment, preference of therapy would be
• Evidence regarding the use of GLP-1 RA and SGLT2i in elderly SGLT2i or DPP4i as add on therapy with metformin. Some DPP4i need
T2DM patients has emerged recently. These classes provide dose adjustment as per eGFR; linagliptin and teneligliptin do not require
good glycemic control in patients with T2DM and can reduce any dose adjustment in renal disease.301–304
CV risk. However, certain drawbacks such as cost, discomfort of • Repaglinide is another agent which may be used across all stages of
injection and weight loss with GLP-1 RA, and increased risk of renal insufficiency. Use of pioglitazone is restricted in CKD; due to the
genital mycotic infections and urinary tract infections, hypovole- risk of fluid retention and congestive heart failure (CCF).305,306
mia, postural hypotension, euglycemic ketoacidosis, and weight • Short acting SUs like glipizide and gliclazide are preferred in patients
loss with SGLT2i may limit their usage in some frail elderly with moderate/severe renal impairment. Furthermore, in mild/moderate
T2DM patients.281 renal impairment, gliclazide MR and glimepiride can also be used,
• Evidence suggests that basal insulin analogues such as glargine, detemir preferably at lower doses.280. However, in general, SUs are better
and degludec are effective and safe with less risk of hypoglycemia and avoided in renal impairment.
• Although GLP-1 RA, especially liraglutide, dulaglutide and oral semag- of SUs and metformin cannot achieve the desired target. Conventional in-
lutide are recommended up to eGFR 15 ml/min, owing to their GI sulin can be used at any stage considering its efficacy and cost.
adverse effect, their use in renal insufficiency patients is limited.305
• AGIs can be used in patients with mild to moderate renal disease Glycemic status
(eGFF>30 ml/min).306 • The order of glucose-lowering agents according to their efficacy of
• Insulin can be used in any stage of renal insufficiency. Insulin analogues HbA1c reduction are insulin, SUs, Metformin, GLP-1 agonists,
are preferred over conventional insulins,307 however, insulin doses may SGLT2i, pioglitazone, DPP-4 inhibitors, glinides and AGIs.272,328–330
require reduction with falling eGFR and HbA1c targets also have also to
be individualised.308,309 Hypoglycemia concern
• Refer to CKD section for use of SGLT2i in patients with CKD. • Hypoglycemia is an important limiting factor during treatment course of
diabetes while targeting good glycemic control.
Duration of diabetes • Insulins, Sulfonylureas and glinides have an increased risk of moderate
• Patients with long-standing T2DM are difficult to treat because these to severe hypoglycemia compared with other classes of agents in
patients often lack sufficient β-cell function to respond to secreta- monotherapy.328,331
gogues. Additionally, they may have other comorbidities, including • While initiating DPP-4 inhibitor on a background of secretagogues such
renal impairment.310 as SUs, the dose of SUs needs to be reduced and close monitoring of
• Insulins are often used in patients with long-standing diabetes to address blood glucose is necessary.332,333 Similarly, while initiating SGLT2i on
insulinopenic states.311 a background of insulin or secretagogues, the dose of insulin or secre-
• Incretin-based therapies, particularly GLP-1 RA, also lower HbA1c tagogues needs to be reduced.333
significantly and have lower risks of hypoglycemia than insulin.311 • In patients with a history of hypoglycemia or for those at high risk of
• SGLT2i may also be useful as add on agent due to their insulin inde- hypoglycemia, GLP-1 agonists or SGLT2i or DPP-4 inhibitors or AGIs
pendent action.312 or pioglitazone should be considered as first choice with metformin.334
• AGI’s can be also effective sometime owing to their beta- cell indepen- • Patients prone to hypoglycemia should not preferably be put on glinides,
dent actions. SUs or insulin, since there are greater chances of hypoglycemia with
these agents.
Established cardiovascular diseases • Individuals in whom hypoglycemia further poses risk include:
• The UKPDS showed that intensive glycaemic control can reduce mi- - Patients with established cardiovascular disease
crovascular complications and to some extent CVD risk in patients with - Elderly patients
T2DM.313 - Patients suffering from CKD and those who cannot perform SMBG
• In patients with established CVD, GLP-1 RA and SGLT 2i with proven without the help of others
efficacy may be preferred.314–320 - Patients who stay alone, especially in remote areas
• In patients with heart failure and CKD, SGLT2i or GLP-1 RA may be - Patients with shortened life expectancy
preferred unless contraindicated.314,315,319,321 - Patients having documented hypoglycemia unawareness
• Pioglitazone has been shown in few studies to reduce CVD risk,322,323 - Autonomic neuropathy
however, it should not be used in patients with heart failure324 or those
with low ejection fraction.325 Implementations
• Glimepiride or Gliclazide MR is preferred over conventional sulfonyl- The health impact of T2DM is well known, and its management has
ureas in patients at increased risk of CVD or with established substantial effects on individual and societal health, psychological well-
CVD.280,326,327 being, quality of life, and economic repercussions. Clinical practice rec-
• AGIs have demonstrated CV Risk reduction by reducing Inflammation ommendations in diabetes management are tools for healthcare providers
& post prandial hyperglycemia so could be a good option in these pts that can ultimately improve health across populations; however, for im-
with ASCVD after Metformin. proved outcomes, diabetes care must also be individualized for each
patient. There is no ‘one-size-fits-all’ treatment for patients with T2DM,
Financial concern and diabetes management should be individualized. The ADA also high-
• Considering that many Indian patients have to pay for their treatment lights the importance of patient-centered care, which is respectful of and
and OPD visits out of their pocket and the treatment also needs to be responsive to individual patient preferences, needs, and values and en-
continued lifelong, cost of therapy also plays a crucial role in T2DM sures that the patient is involved in all clinical decisions.335 An individ-
patients from the Indian subcontinent. ualized therapy for T2DM could serve as a “real-world” approach, pro-
• Sulphonylureas can be a good addition to metformin considering their cost, viding care that is responsive to individuals’ specific and unique needs,
particularly in the light of the recent CAROLINA trial demonstrating the CV preferences, and values, and also helping to combat adverse long-term
neutrality of glimepiride compared to linagliptin.326 Pioglitazone or inexpen- outcomes.
sive DPP-4 inhibitors or SGLT2i can also be considered when combinations
RSSDI Therapeutic Wheel Background

Patients with poorly controlled diabetes frequently develop micro-and
macro-vascular complications. Evidence from extensive controlled clini-
cal studies suggests that intensive glycemic control can significantly re-
duce their risk of development and/or progression336–340. Until recently,
the predominant focus of diabetes treatment has been on lowering HbA1c
levels, with emphasis on FPG341,342. However, control of fasting hyper-
glycemia alone is insufficient to obtain optimal glycemic control as evi-
dence suggests that reducing PPG excursion is essential or perhaps more
important for achieving desired glycemic targets343. It is understood that
HbA1c is primarily impacted by FPG when it is away from the target. As
it comes closer to the target, PPG starts taking the upper hand and con-
tributes predominantly. Therefore, patients who achieved 2-h PPG within
the reference limit will better accomplish target HbA1c values than those
who realized FPG within the recommended range344. In Indians, the PPG
remains relatively high across the HbA1c spectrum and very high even at
higher HbA1c values345–347. The relative contribution of postprandial
hyperglycemia to HbA1c levels in patients with T2DM is higher than
FPG levels when HbA1c is <7.5%, decreasing progressively as HbA1c
levels increase348. Therefore, targeting PPG and FPG is ideal for achiev-
ing optimal glycemic control. The purpose of these recommendations is
to assist clinicians in developing strategies to consider and effectively
manage post-meal glucose in people with T2DM in Asian countries.
Considerations
India has a high prevalence of diabetes, and the onset of diabetes is a
decade early. Postprandial hyperglycemia is more prominent in Indians
From innermost to outermost: due to traditional high diets with the high glycemic index. Literature is
A - Age = Advancing age limited regarding postprandial hyperglycemia despite its substantial role
B - BMI = Increasing BMI
C - CKD = Advancing CKD in micro-and macro-vascular complications.
D - Duration of Diabetes = Increasing duration
E - Established CVD = Low CVD risk to Established CVD risk
F - Finance = Adequate to Limted Rationale And Evidence
G - Glycemic Status = Worsening glycemia control Definition of postprandial hyperglycemia
H - Hypoglycemia = Hypoglycemia concern
• ADA 2019 and the IDF 2018 define postprandial hyperglycemia as a
AGI, Alpha-glucosidase inhibitor; DPP4, Dipeptidyl Peptidase-4 (DPP 4) Inhibitors; DPP4-L, 2-h plasma glucose level of >200 mg/dL (11.1 mmol/L) during an oral
Dipeptidyl Peptidase-4 Inhibitors-Linagliptin; GL, Glinides; GLP, Glucagon-like peptide-1 receptor
agonist; PIO, Pioglitazone; SGLT, Sodium-glucose Cotransporter 2 Inhibitors; SSu, short acting glucose tolerance test (OGTT). It recommends using glucose load
sulphonylureas; Su, Sulphonylurea; LSM, lifestyle modification equivalent to 75 g of anhydrous glucose dissolved in water as prescribed
Note: Hierarchy of therapy is depicted in clock-wise manner by WHO273,349.
GLPs must be used based on costs. Any of the drugs can be used in the green. For other zones, drugs
must be used in the given order.
• Asian Indians displayed a marked rise in prandial glucose excursion
after consumption of 75 g of bread meal compared to their Caucasian
counterparts350,351.
POSTPRANDIAL HYPERGLYCEMIA • Elevations in PPG are due to decreased first-phase insulin secretion,
reduced insulin sensitivity in peripheral tissues, and consequently de-
Recommendations creased suppression of hepatic glucose output after meals, unsuppressed
glucagon levels, and deficiency of intestinal incretin hormones GLP-1
and (glucose-dependent insulinotropic polypeptide) GIP341.
Recommended Care • The causes of postprandial hyperglycemia are influenced by many fac-
tors, including a rapid flux of glucose from the gut, impaired insulin
• Postprandial hyperglycemia is defined as having postprandial glucose level higher release, endogenous glucose production by the liver, and peripheral
than the target after a usual meal and on medications (if any).
IR352.
• PPG should be measured 2-h after the start of a usual meal and medications (if any).
• Target PPG: 160 mg/dL as long as hypoglycemia is avoided.
• Recent evidence suggests that the value of glycemia at 1-h during an
• Both non-pharmacologic and pharmacologic therapies should be considered OGTT is a stronger predictor of developing diabetes than the value at 2-
- MNT: diet with low glycemic load is recommended h353–355. Therefore, in clinical practice, targeting PPG at 1-h instead of
- AGIs (acarbose, miglitol or voglibose), DPP4 inhibitors, SGLT2 2-h could significantly reduce the risk for CVD. The 1-h PPG has been
inhibitors or GLP-1 analogues (preferably short-acting) as the first add-
correlated with increased left ventricular mass, left ventricular diastolic
on to metformin therapy
- Glinides and short-acting sulfonylureas as alternative options dysfunction, and carotid intima-media thickness (CIMT)356–359.
- Rapid-acting insulin analogues may be considered over regular insulin when However, measurement of plasma glucose after 1 hour of glucose load
postprandial hyperglycemia is a concern, especially when the risk of was higher than 2-hour value and correlated better with hepatic fat in
hypoglycemia is high. non-diabetic obese adults.360
• Combination therapy of AGI with other agents may be considered.
• SMBG should be considered as it is the most practical method for monitoring
• Evidence from an Indian study based on patients with a history of
postprandial glycemia. T2DM for more than 25 years suggests that postprandial hyperglycemia
• Efficacy of treatment regimens should be monitored frequently to guide therapy was associated with an increased risk of diabetic nephropathy and neu-
towards achieving PPG targets. ropathy345,361. And Kumamoto’s study suggested reductions in retinop-
• Glycemic Index, as well as dietary insulin index of food items, may be considered for athy and nephropathy with reduced PPG [Figure].340,362
better PPG control.
• Elderly patients on SU were randomized to continue with SU or Figure 5: MNT to prevent postprandial hyperglycemia. (MNT: Medical
repaglinide. After 16 weeks, Glycated Albumin and GA/HbA1c ratio nutrition therapy)
was improved in repaglinide recipients. 363
Strategies to prevent postprandial hyperglycemia
Non-pharmacological
• Physical activity and MNT [Figure] are the cornerstones of non-
pharmacologic therapy in T2DM patients.362
• A randomized crossover study showed that in T2DM patients, walking
after meals is more effective for lowering postprandial glycaemia.374
• Traditional Asian Indian and Chinese diets are carbohydrate-rich (as
high as 80% of the macronutrient composition) with high glycemic
index values.375 Consumption of rice is very high in South India, which
is associated with a 4–5 fold increase in the risk of diabetes.376 The
higher carbohydrate load in the Indian diet leads to greater PPG excur-
sion, increased glucosidase and incretin activity in the gut, which leads
to higher lipemic peaks and associated CVD.375 Evidence suggests that
diets with low glycemic index values are beneficial in controlling post-
prandial hyperglycemia.341,377,378 On the other hand, bean-based break-
fast was associated with fewer glycemic excursions throughout the day
compared to rice-based breakfast, which is predominant in most parts of
Figure 4: Secondary complications of postprandial hyperglycemia364,365 India and Asia.379 For details, please refer to the MNT and lifestyle
section
Addressing postprandial hyperglycemia • Focusing on carb counting is not sufficient for controlling pp sugar.
The HEART2D (Hyperglycemia and Its Effect After Acute Myocardial Protein and fat content also play a role in augmenting insulin secretion.
Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes The dietary insulin index should be utilized for glycemic manage-
Mellitus) and the NAVIGATOR (Nateglinide and Valsartan in Impaired ment.380
Glucose Tolerance Outcomes Research) study could demonstrate the
direct benefit of lowering postprandial hyperglycemia in reducing CVD Pharmacological
in patients with T2DM.366–368 However, emerging evidence indicates that • Based on limited Indian evidence available from literature, the panel
agents that target PPG show significant positive trends in risk reduction relied on expert opinion for pharmacological management of postpran-
for all selected CV events. Findings from the Study to Prevent Non- dial hyperglycemia, which includes the following:
Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial highlight that - GLP-1 analogues are effective in controlling postprandial glucose either
treating people with IGT with acarbose significantly reduced the risk of when used in association with metformin or part of a combination therapy
CVD and hypertension.369 The Acarbose Cardiovascular Evaluation including basal insulin. The short acting GLP-1 agonists (exenatide and
(ACE) trial highlighted that there was no significant impact of acarbose lixisenatide) are preferred when isolated postprandial hyperglycemia is
therapy in reducing the risk of major CV events. However, the incidence present.
of diabetes was reduced, which may mitigate cardiovascular risk in the - The ultrafast acting insulin analogue has demonstrated significant ben-
longer term by delaying the onset of T2DM in the high-risk efits in reducing 1-h PPG following mealtime administration.
population.370 - DPP-4 inhibitors have shown significant benefits in reducing PPG ex-
Postprandial hyperglycemia is an important pathophysiological state con- cursions and lowering HbA1c.
tributing to the several secondary complications including CV events. - Use of glinides is limited to the treatment of postprandial hyperglycemia
Management of postprandial hyperglycemia is central to long-term gly- only if sulfonylureas are contraindicated, or economic consideration pro-
cemic control and an essential part of CVD prevention T2DM. Therefore, hibits the use of newer and expensive agents.
it should be routinely monitored in T2DM patients using 2-h post-meal. - AGIs (acarbose, miglitol, and voglibose) can be used as a first-line drug
Thus, screening for prediabetes and monitoring the glycemic control in in early T2DM and in combination with nearly all established OADs and
patients with T2DM should include PPG as a predictive marker for all- insulin. Moreover, AGIs tend to inhibit carbohydrate absorption from the
cause premature death, CV risks, and FPG and HbA1c levels.370–372 The gut which can be of particular importance in Indian settings where there
level of implementation of routine screening for post-meal hyperglyce- are increased odds for PPG and lipid excursion due to consumption of
mia, using the OGTT, should be improved in the Asia-Pacific region, diets with the high glycemic index. In a prospective randomized trial on
combined with broader use of effective interventions to manage postpran- T2DM from five centers across Korea, patients were inadequately con-
dial hyperglycemia.373 trolled on Metformin + Sitagliptin, acarbose was added as 2nd add-on.
Acarbose was found to be a safe and effective add-on to Metformin +
Sitagliptin for improving glycemic parameters.381
Implementation
Frequent monitoring of glucose levels using techniques such as SMBG
can significantly improve glycemic control besides detecting PPG excur-
sion. SMBG is currently the optimal method for assessing plasma glucose
levels. Evidence suggests that structured SMBG followed by therapeutic
interventions results in more significant HbA1c reduction in individuals
with T2DM compared with programs without structured SMBG.382–384
Therefore, the panel suggests including SMBG with appropriate patient
education for optimal management of post-meal hyperglycemia.
Although, SMBG estimates the average glucose accurately, it underesti-
mates the glucose excursions. A continuous glucose monitoring system
(CGMS) provides information on glucose levels, patterns and trends,
reflecting the effects of medication, meals, stress, exercise, and other Pathogenesis of these life-threatening hyperglycemic emergencies is re-
factors that affect glucose levels. The CGMS could also be a useful lated to absolute, or relative insulin deficiency and an increase in insulin
method to detect postprandial hyperglycemia and to improve therapeutics counter-regulatory hormones that lead to altered metabolism of carbohy-
management in patients with T2DM.347,385–387 drate, protein, and fat and varying degrees of osmotic diuresis and
ACUTE METABOLIC COMPLICATIONS Table 11: Diagnostic criteria for diabetic ketoacidosis and
hyperglycemic hyperosmolar state
Hyperglycemic Crisis (Diabetic Ketoacidosis and Hyperosmolar
Hyperglycemic State) Measure DKA HHS
Recommendations Plasma glucose level (mg/dL) >250 >600
Arterial or venous pH <7.30 >7.30

Recommended Care
Serum bicarbonate level (mmol/L) <15 >15
• Treatment individualization based on careful clinical and laboratory assessment is
needed. Urine or blood ketones Positive Negative or low
• Management goals should include:
- Restoration of circulatory volume and tissue perfusion Urine or blood βhydroxybutyrate
- Correction of electrolyte imbalance and reversal of ketosis ≥3 <3
(mmol/L)
- Resolution of hyperglycemia
- Identification and prompt treatment of precipitating events Effective serum osmolality
Variable >320
- Avoiding complications of therapy, particularly cerebral oedema (mOsm/kg)
- Prevention of recurrent episodes
• Meticulous monitoring of clinical and biochemical responses using a flow chart is Anion gap (mmol/L) >12 <12
essential to document hour-by-hour clinical observations, intravenous and oral
+
medications, fluids, and laboratory results. nitroprusside reaction method, defined as 2[measured Na (mEq/L)]
• Admission to an intensive care unit or comparable setting with adequately + glucose (mg/dL)/18, Canion gap: (Na+) - [(Cl− + HCO - (mEq/L)].
trained nursing and medical staff and 24 h laboratory services for frequent
monitoring is warranted for children <2 years of age and in case of 3
compromised circulation, coma, and risk of cerebral edema.
• Emergency assessment should follow the general guidelines of advanced life
support, with particular attention to airway and breathing patterns, the severity of DKA: Diabetic ketoacidosis, HHS: Hyperglycemic hyperosmolar state
dehydration, mental status, source of infection, level of consciousness (Glasgow Dehydration, ketosis, and acidosis394 termed together as decompensated
coma scale), and frequent monitoring of clinical and laboratory parameters.
• If laboratory measurement of serum potassium is delayed, perform an
diabetes, the prevalence and mortality for DKA and HHS remain indis-
electrocardiogram for baseline evaluation of potassium status. A cardiac monitor tinct across various age, gender, and racial groups of hospitalized dia-
should be used for continuous electrocardiographic monitoring to assess T waves betics. If not interrupted by exogenous insulin, fluid, and electrolyte ther-
for evidence of hyper-or hypo-kalemia and arrhythmias. apy, it would lead to fatal dehydration, hypoperfusion, and ultimately
• In the unconscious or severely obtund patient, secure the airway and empty the
metabolic acidosis.
stomach by continuous nasogastric suction to prevent pulmonary aspiration.
• Fluid replacement should begin before starting insulin therapy to restore peripheral In DKA, insulin deficiency and ketoacidosis are the prominent features of
circulation. the clinical presentation, and insulin therapy is the cornerstone of therapy
• Adequate oxygenation should be maintained using supplemental oxygen to patients [Tables 9 and 10]. Severe hyperglycemia, osmotic diuresis, and dehydra-
with severe circulatory impairment or shock. tion with altered mental status without significant acidosis characterize
• Give antibiotics to febrile patients after obtaining appropriate cultures of body fluids.
• The rate of fluid administration should not exceed 1.5-2 times the usual daily
HHS. Fluid replacement remains the cornerstone of therapy for HHS. A
maintenance requirements. considerable overlap has been reported in more than one-third of patients
• Insulin administration should begin 1-2 h after starting fluid replacement therapy. exhibiting mixed DKA and HHS features [Table #]. Because the three-
• In critically ill and mentally obtunded patients, continuous intravenous insulin is the pronged approach to therapy for either DKA or HHS consists of fluid
standard of care. administration, intravenous insulin infusion, and electrolyte replacement,
• Bicarbonate administration is not recommended except for the treatment of life-
threatening hyperkalemia. Patients with multiple risk factors for cerebral edema, have
and mixed cases are managed using the same method. ICU admission is
mannitol or hypertonic saline at the bedside, and the dose should be calculated indicated in the management of DKA, HHS, and diverse patients in the
beforehand. If neurologic status deteriorates acutely, hyperosmolar therapy should be presence of cardiovascular instability, inability to protect the airway,
given immediately. obtundation, the presence of acute abdominal signs or symptoms sugges-
tive of acute gastric dilatation, or if there is not adequate capacity on the
floor unit to administer the intravenous insulin infusion and to provide the
Background
frequent and necessary monitoring that must accompany its use [Figure 6
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state
and Table 13].
(HHS) represents the most common and severe acute metabolic compli-
cations of diabetes. Despite well-developed diagnostic criteria and treat-
Considerations
ment protocols, DKA and HHS are associated with substantial morbidity
Treatment of patients with DKA and HHS is associated with substantial
and mortality.388 The overall DKA mortality recorded is <1%, but a
mortality and healthcare costs. In a developing country like India, due to
higher rate is reported among patients aged >60 years and individuals
poor socio-economic status, many patients with T2DM tend to have poor
with concomitant life-threatening illnesses.388–390 HHS typically occurs
compliance and poor glycemic control. Thus any precipitating factor
in older patients with T2DM with an intercurrent disease such as infec-
manages to land them in a state of hyperglycemic emergencies, including
tion, surgery, or ischemic events and is associated with a higher mortality
DKA and HHS.
rate than DKA. The mortality rate with HHS is almost 10-fold more
elevated when compared with DKA.391–393
Table 13: Management of acute metabolic complications
Fluid replacement therapy
In the absence of cardiac compromise, isotonic saline (0.9% NaCl) is infused at a rate of 15-
20 mL/kg/h or 1-2 l over 1-2 h for prompt recovery of hypotension and/or hypoperfusion
Continue with 0.9% NaCl at a similar rate if patient is hyponatremic or switch to 0.45% NaCl
infused at 250-500 mL/h if the corrected serum sodium is normal (eunatremia) or elevated
(hypernatremia)
When plasma glucose level is <200 mg/dL, change to 5% dextrose in saline as long as the
insulin infusion continues.
Insulin therapy
Start insulin infusion 1-2 h after starting fluid replacement therapy (after initial volume
expansion), and serum potassium restored to>3.3 mEq/l
Figure 6: Algorithm for the management of DKA and HHS. DKA:
A regular human insulin IV bolus of 0.1-0.15 U/kg followed by continuous insulin infusion at
Diabetic ketoacidosis; HHS: Hyperglycemic hyperosmolar state; IV: 0.1 U/kg/h
Intravenous; SC: Subcutaneous
IV bolus is avoided in children as it may increase the risk of cerebral edema and can
exacerbate hypokalemia.
Table 12: Monitoring of clinical signs and biochemical investigations When glucose level reaches 200 mg/dL in DKA or 300 mg/dl in HHS, reduce insulin rate to
0.02-0.05 U/kg/h. After that, adjust the rate to maintain a glucose level of 150-200 mg/dL in
DKA and 250-300 mg/dL in HHS
Plasma glucose and HbA1c levels Venous pH
Continue insulin infusion until resolution of ketoacidosis
BUN, creatinine, electrolytes
(including bicarbonates) with a Subcutaneous rapid-acting insulin analogs (lispro and aspart) every 1-2 h. might be an
Fluid input and output alternative to IV insulin in patients with mild to moderate DKA
calculated anion gap, and
hematocrit
Initial dose subcutaneous: 0.3 U/Kg, followed one h later at 0.1 U/Kg every one h, or 0.15-0.2
Serum osmolality Vital signs (heart rate, respiratory rate, BP) U/kg every two h
Neurological observations for warning signs and Potassium replacement

Serum and urinary ketones
symptoms of cerebral edema
If the patient is hypokalemic, start potassium replacement at the initial volume expansion and
Arterial blood gases ECG, chest X-ray, USG abdomen and pelvis before starting insulin therapy. Otherwise, begin after initial volume expansion and concurrent
with insulin therapy.
USG: Ultrasound, BUN: Blood urea nitrogen, ECG: Electrocardiogram, BP: Blood pressure,
HbA1c: Glycosylated hemoglobin With initial rapid volume expansion, a concentration of 20 mmol/l should be used.
The maximum recommended rate is 0.5 mmol/kg/h.
The treatment goal is to maintain serum potassium levels of 4-5 mEq/l.
Bicarbonate therapy
Not routinely recommended; only indicated in adults with severe acidosis with pH <6.9
If pH <6.9, consider 100 mmol (2 ampules) in 400 ml sterile water with 20 mEq KCI
administered at a rate of 200 ml/h for two h.until pH is ≥7.0.
If the pH is still <7.0 after this is infused, we recommend repeating the infusion every two h.
until pH reaches >7.0.
Transition to subcutaneous insulin
To prevent recurrence of ketoacidosis or rebound hyperglycemia, consider the overlap of IV

insulin for 15-30 min (with rapid-acting insulin) or 1-2 h (with regular insulin) or longer (with
intermediate or long-acting insulin) after subcutaneous insulin is given.
The most convenient time to change to subcutaneous insulin is just before mealtime.
For patients treated with insulin before admission, restart previous insulin.
Regimen and adjust dosage as needed.
For patients with newly diagnosed DM, start the total daily insulin dose at 0.5-0.8 U/kg/day.
Consider multi-dose insulin given as a basal and prandial regimen.
SGLT2i: avoid permanently.
DKA: Diabetic ketoacidosis, HHS: Hyperosmolar hyperglycemic state, IV: Intravenous, DM:
Diabetes mellitus.
HYPOGLYCEMIA Furthermore, Kalra et al. stated that diabetes patients with severe hypo-
glycemia are associated with a sixfold increase in deaths over those not
Recommendations experiencing it.399 Therefore, urgent steps must be taken with some cor-
rective measures against hypoglycemia in T2DM patients to minimize the
Recommended Care
burden. Following are some causes and risk factors for hypoglycemia
[Table 14].399
• The risk of hypoglycemia should be assessed during every visit in patients with T2DM
by using questionnaires. Considerations
• The patient should be well educated and informed regarding:
- The symptoms, causes, and risks associated with hypoglycemia
Factors such as the intensity of hypoglycemic risk, patient characteristics,
- Usage of SMBG tools with frequent monitoring, especially for patients taking drug usage, fasting, and patient education should be considered while
insulin framing the recommendations for hypoglycemia management in patients
- Insulin dose adjustment considering blood glucose values with T2DM.
• Strict monitoring of hypoglycemic episodes is recommended for patients taking
insulin, sulfonylureas, or meglitinides alone or in combination.
• Modern insulins or sulfonylureas should be used instead of traditional drugs in
Table 14: Causes and risk factors for hypoglycemia 397,403
patients with a high risk of hypoglycemia.
• Oral glucose (15-20 g) is preferred in conscious hypoglycemic patients (glucose alert Causes Risk factors
value of <70 mg/dL). Repeat the treatment if SMBG shows persistent hypoglycemia
after 15 min. The patient should consume a meal or snack once SMBG returns to Metabolic defects Glucose-lowering drugs (especially SU/insulin)
normal to prevent the recurrence of hypoglycemia
• Intramuscular glucagon or intravenous glucose is preferred for unconscious patients Autoimmune conditions
Increased glucose utilization or decreased glucose production
or patients with clinically significant hypoglycemia (glucose alert value <54 Dietary toxins
mg/dL). Repeat intramuscular or subcutaneous glucagon dose of 0.5 mg if there is Female gender
no symptomatic improvement. Alcohol consumption
Inborn errors of metabolism
• Glucagon is to be avoided in patients with sulfonylurea-induced hypoglycemia. Stress Infections
Sleep
• Treatment should be modified in the event of hypoglycemia repeatedly Starvation
Long duration of diabetes Extremes of age
occurring at a particular time of the day or in the event of hypoglycemia Severe excessive exercise
Progressive insulin deficiency
unawareness.
• Hypoglycemia occurring in the setting of advanced kidney disease (CKD stage 4 or 5 Intensive glycemic control on OADs and insulin (alone or in
requires relatively longer observation for the avoidance of recurrence even long after combination)
initial corrective measures are taken.
Skipping of meals
DKD, hepatic impairment
Cortisol Insufficiency
Limited Care
Autonomic Failure
• All patients with risk of hypoglycemia should be enquired about symptomatic and
asymptomatic hypoglycemia at each visit. Cognitive impairment
• Patients and their family members should be well educated about the
Polypharmacy
identification and management of hypoglycemia, especially night-time
hypoglycemia. ACE and β-blockers
• Hypoglycemia should be strictly managed and monitored in special situations such as
the elderly, pregnancy, fasting, and metabolic disorders. ACE: Angiotensin-converting-enzyme, DKD: Diabetic kidney disease,
OADs: Oral antidiabetics, SU: Sulfonylureas
Background
Rationale and Evidence
Hypoglycemia is a significant cause of concern with some antidiabetic
Identification
drugs during glycemic management in patients with T2DM.395 However,
• Symptoms of hypoglycemia include but are not limited to excess sweat-
the extent of hypoglycemia varies with different antidiabetic drugs' phar-
ing and hunger, dizziness, blackout, fainting, fatigue, light-headedness
macokinetic and pharmacodynamic properties. The International
or shakiness, nausea or vomiting, mental confusion, unresponsiveness,
Hypoglycemia Study Group categorizes hypoglycemia into three catego-
and dryness or tingling lips.395
ries based on the glycemic criteria.396
• Nocturnal hypoglycemia is suspected in night-time sweating, hunger,
and anxiety. Nightmares, early morning headaches, and labile morning
• Glucose alert value (level 1): <70 mg/dL (3.9 mmol/L)
sugars should also alert the physician.404,405
• Clinically significant hypoglycemia (level 2): <54 mg/dL (3.0 mmol/L)
• Some endocrinologists or diabetologists use a three-step approach
• Severe hypoglycemia (level 3): no specific glucose threshold.
(Whipple’s Triad) to diagnose hypoglycemia. It includes:
- Low blood glucose level
The prevalence of hypoglycemia in patients with T2DM in India is rela-
- Symptoms of hypoglycemia at the time of the low glucose level
tively high. A recent cross-sectional study reports that nearly 96% of
- Symptom relief with the treatment of hypoglycemia.
patients (out of 366 patients) were associated with at least one or other
symptoms of hypoglycemia (dizziness, weakness). Furthermore, patients
Management
taking insulin in addition to OADs were at higher risk than patients taking
• Management of hypoglycemia can be subdivided into three aspects:
OADs alone (OR, 2.3; p <0.01).397 Meanwhile, another cross-sectional
- Prevention of hypoglycemia
study including 1650 patients from South India revealed that the cumu-
- Treatment of hypoglycemia
lative incidence of institutional hypoglycemia was 12.36%, among which
- Adjustment or withdrawal or modification of current antidiabetic
26.96% had asymptomatic episodes.398 Severe hypoglycemia can lead to
regimen.
several diabetes-related short-and long-term complications such as neu-
• Glucagon in solution form is known to rapidly degrade to form β-sheet-
rocognitive dysfunction, retinal cell death, and loss of vision399 and may
rich amyloidogenic fibrils. The specific type of degradation products
lead to coma or death if not reversed.395 The ACCORD and ADVANCE
varies with time of exposure/aging, concentration, pH, shear, tempera-
trials and other pieces of evidence reported that severe hypoglycemia was
ture, and presence of certain excipients. The generation of degradation
directly associated with mortality in patients with T2DM.400–402
products presents two problems in the clinic: (i) loss of efficacy over • Glucagon to be avoided in sulfonylurea-induced hypoglycemia.
time and (ii) potential cytotoxicity/neurotoxicity associated with • Caretakers of hypoglycemia-prone diabetes patients (family members,
amyloidogenic fibrils.406 roommates, school personnel, child-care providers, correctional institu-
• The ADA guides protocol to treat severe hypoglycemia treatment protocol; tion staff, or co-workers) should be well instructed on using glucagon
for conscious individuals with BG less than 70 mg/dL, 15 to 20 g of pure kits, including where the equipment is located and when and how to
glucose is the preferred treatment, although any carbohydrate with glucose administer glucagon.395
is appropriate. If the patient continues to be hypoglycemic 15 minutes after • Acute glycemic response correlates better with the glucose content than
treatment, this treatment should be repeated. Once the patient is no longer with the carbohydrate content of food. Therefore, pure glucose is the
hypoglycemic with a BG of 70 mg/dL or greater, the patient should con- preferred treatment.[345] Fifteen minutes after glucose administration, an
sume a snack to prevent recurrent hypoglycemia. This is commonly known SMBG should be done, and the treatment should be repeated if hypo-
as the “15-15 rule”. Because of its hypertonicity, administration of IV D 50 / glycemia persists. The patient should be advised to eat a regular meal or
25 carries an increased risk of extravasation.407 snack to prevent hypoglycemia recurrence.421
Prevention of hypoglycemia Implementations

• Hypoglycemia prevention is preferable to treatment, as it is much more Patient empowerment with hypoglycemia monitoring tools, hypoglyce-
likely to avoid severe events and economic burdens.408 Hypoglycemia mia risk awareness, available preventive strategies, and a physician-
prevention requires a combined effort from a physician and the patient. patient collaboration treatment plan can reduce the frequency and inten-
Patient education, patient counseling, and continuous blood glucose sity of hypoglycemia.
monitoring are the critical factors that need to be considered to prevent
hypoglycemia in patients with diabetes. Evidence suggests that a proper
and structured diabetes education helps in reducing diabetic complica- CHRONIC COMPLICATIONS 1: RETINOPATHY,
tions, including hypoglycaemia.409–412 NEUROPATHY, DIABETIC KIDNEY DISEASE
• Furthermore, interventions targeting health beliefs and attitudes about
hypoglycemia and diabetes self-management can be more effective than RETINOPATHY
knowledge-centered patient education, focusing on symptom percep-
tion in reducing unawareness of hypoglycemia.399 Patients receiving Recommendations
insulin for the treatment of T2DM can be benefitted by adjusting insulin
doses following the SMBG procedure.399–405,408–413 In addition, a Recommended Care
cross-sectional study from India reports that 85% of patients were tak-
ing timely meals to prevent hypoglycaemia.397 Stratifying patients ac- • Documentation of the formal history of vision and visual acuity, either by
cording to age and avoiding very tight glucose control in elderly patients recording it on a sheet or electronic medical record (EMR) should be made
mandatory first at the time of diagnosis and then periodically.
(>70 years) and very young children <5 years of age will help to prevent • Ensure that examination of the eyes of people with T2DM is performed around
hypoglycemia in these high-risk people. the time of diagnosis and then routinely every 1-2 years as part of a formal recall
process:
Adjustment or withdrawal, or modification of the ongoing antidiabetic - Measure and document visual acuity, corrected with glasses or pinhole
- Record ocular pressure and assess the condition of the iris and lens
regimen
- Assess retinopathy:
• Most antidiabetic agents can produce hypoglycemia; however, the in- » Using retinal photography through dilated pupils, performed by an
tensity depends upon their mechanism of action. Insulin, sulfonylureas, appropriately trained healthcare professional, or
and meglitinides, due to their glucose-independent mechanism of ac- » Through examination by an ophthalmologist
tion, cause a high risk of hypoglycemia.399 • Discuss the reasons for an eye examination with the person with diabetes.
• Counselling must include components on smoking, diet, alternative medicines,
• The UK Hypoglycemia Study Group report that severe hypoglycemia exercise, and appropriate choice of drugs for BP and Lipids.
increased from 7% to 25% in patients treated with insulin for <2 years • Counsel women who are planning pregnancy on the risk of progression of retinopathy
and those treated for >5 years.414 However, modern insulin analogs report a during pregnancy, especially if there is pre-existing retinopathy. •
lower incidence of hypoglycemia than traditional human insulins.415–417 • Ensure regular follow-up throughout pregnancy and up to 1 year post-partum.
• Modern sulfonylureas like gliclazide MR and glimepiride are associated • Use tropicamide to dilate pupils, unless contraindicated (rule out history of
glaucoma), after discussing the implications and obtaining agreement of the person
with lesser hypoglycemic episodes among all sulfonylureas.418,419 with diabetes.
Meglitinides were reported to inflict high rates of hypoglycemia.420 In • Classify the findings of eye examination as required: routine review, earlier review or
special situations like the elderly, fasting, metabolic disorders, and preg- referral to an ophthalmologist (if not making the examination).
nancy, the dose of these drugs should be adjusted or modified to avoid • The following frequency of screening is suggested:
further complications. Furthermore, avoid/reduce the insulin dose in - 1-2 years, if no retinopathy, depending on clinical situation
- 12 months, if minimal unchanged retinopathy
people with CKD who tend to develop hypoglycemia. - 2-4 months, after any active ophthalmic intervention
- 3-6 months, if worsening since last examination
Treatment of hypoglycemia - More often during pregnancy
• 15 to 20 g of carbohydrates (four teaspoons of sugar or glucose) can be
given orally to a conscious patient with hypoglycemia; if unconscious,
glucagon injection intramuscularly or glucose injection intravenously
can be preferred.395–399
• The following situations require specialist referral: with young-onset type 2 diabetes in India), DR was prevalent in 6.1% and
- The same day:
5.1% patients, respectively428,429. Moreover, the socioeconomic burden
» Sudden loss of vision
» Evidence of retinal detachment
of DR-induced visual impairment or blindness, particularly in the work-
- Within one week: ing age group, is a serious concern430. Therefore, it is high time to devise
» Evidence of pre-retinal and/or vitreous hemorrhage the means of managing DR and bring the problem under control431. A
» New vessel formation or rubeosis iridis systematic approach to health education, creating awareness among pa-
» Inability to see or assess disc or fovea
tients and various health personnel, and matching it with appropriate
» Raised ocular pressure
- Within 1-2 months: screening and service delivery mechanisms will go a long way. Early
» Advanced retinal lesions (4:2:1 rule) detection and management of DR with quick referrals and highly coordi-
» Microaneurysms or retinal hemorrhages in 4 quadrants nated teamwork between the endocrinologists, ophthalmologists, neurol-
» Venous beading in two quadrants ogists, and nephrologists could reduce the prevalence of DR in India432.
» IRMAs in one quadrant
» Unexplained deterioration of visual acuity
Necessary therapeutic measures in managing DR include optimum gly-
» Macular oedema cemic levels, lipid and hypertension control. In severe cases of pre-
» Unexplained retinal findings proliferative DR, laser pan-retinal photocoagulation (PRP) is indicated
» Cataract to prevent the progression of DR and vision loss 433 . Of note,
» Inability to visualize fundus
Implementation of intensive glycemic control can cause transient (early)
• Stepped approach should be adapted to manage hyperglycemia, as intensive
glycemic control can cause transient (early) worsening of symptoms and even
worsening, primarily due to the development of small arteriolar infarcts,
lead to cotton wool spots. which result in the well-known cotton wool spots, particularly in patients
• GLP-1 agonists may initially worsen diabetic retinopathy, and hence must be used with poor control and long-standing disease are at risk. Therefore, a
with caution. calculated and stepped approach should be adapted to manage hypergly-
• Advice that good control of blood glucose, BP and blood lipids, and cessation of
cemia in patients with DR434.
smoking can help to reduce the risk of development or worsening of eye
complications.
• Advice that DR is not a contraindication for use of aspirin, if this is indicated for
prevention of CVD. Rationale and Evidence
• Advise that tests of intra-ocular pressure should be done periodically. Screening
• Explain guarded prognosis about regaining vision after intra-ocular lens (IOL)
surgery in mature/hyper mature cataract because of poor assessment of retina in
• Several guidelines emphasize on eye screening in T2DM, however, it
the presence of mature cataract.
appears they are divided on the frequency of screening. Some recom-
Discourage use of alternative medicines as they can cause further mend annual screening (NICE- UK) while others recommend screening
complications. every 1–2 years (Canadian-Canada, Australian-Australia and SIGN-
Scotland).
• With regard to frequency of screening in limited care setting, the panel
endorsed the ADA recommendation which suggests less-frequent ex-
Limited Care aminations (every 2–3 years) following one or more normal eye
examinations435.
• Use direct fundoscopy through dilated pupils, performed by a healthcare team
• Screening methods for DR include direct and indirect ophthalmoscopy,
member who is adequately trained and has the appropriate experience to assess
retinopathy. slit-lamp bio-microscopy, stereoscopic color film fundus photography,
• Check visual acuity. mydriatic or nonmydriatic digital color, and monochromatic photogra-
• Repeat review, referral and preventative therapy areas for recommended care. phy436–438.
• Less-frequent examinations (every two years) may be considered following one or • In-person clinical exam by an eye care provider is the gold standard for
more normal eye examinations.
• Discourage the use of alternative medicines as they can cause further complications.
diagnosing DR, faster digital retinal imaging acquisition and grading of
DR using fundus images obtained with a nonmydriatic fundus camera is
now being considered a practical, cost-sparing, and feasible screening
Background tool for the early detection of DR, and preventing blindness439.
Diabetic eye disease comprises a group of eye conditions that affect
people with diabetes, such as diabetic retinopathy (DR), diabetic macular Counselling pregnant women
edema (DME), cataract, and glaucoma. • DR is the foremost cause of blindness in women during antenatal period,
DR is a microvascular complication of diabetes and one of the leading and pregnancy increases the short-term risk of DR progression437. The
causes of blindness or vision impairment in India422,423. It affects retinal possible relationship between DR and the perinatal outcome has been
blood vessels and is the most common cause of vision loss among people addressed in several studies440,441. Women with more severe DR were
with diabetes and the leading cause of vision impairment and blindness more likely to develop obstetric complications20,21,, and those with
among working-age adults.424 Visual loss from DR could be due to dia- proliferative changes accounted for a higher incidence of congenital
betic macular edema (DME: swelling in the retinal macula) or prolifera- malformations and/or fetal death441.
tive diabetic retinopathy (PDR). Factors such as longer duration of dia- • As pregnancy can induce progression of DR, the panel recommended
betes and poorer glycemic and BP control were found to be strongly pre-conception counselling for women, clearly explaining the risk of
associated with DR.425,426 progression of DR during pregnancy, especially if they already have
DR has also been linked to cardiovascular mortality in some cases.427 In a proliferative retinopathy. They should be advised on maintaining rea-
cross-sectional study carried out by the All India Ophthalmological sonable glycaemic control before and throughout pregnancy under the
Society, the prevalence of DR was 21.7%, and the rate was high in men guidance of a healthcare professional. In addition, the panel emphasized
(p=0.007), in patients with diabetes duration>5 years (p=0.001), in pa- the need for close follow-up during pregnancy and up to 1 year post-
tients with age>40 years (p=0.01), in insulin users (p=0.001), and in partum and monitoring for progression of DR and co-existing hyper-
patients with a history of vascular accidents (p=0.0014) 422 . tension and renal disease, if any.
Furthermore, in the cross-sectional survey of Indian patients with
T2DM in CINDI (chronic complications in newly diagnosed patients Guarded prognosis after intra-ocular lens surgery
with type 2 diabetes mellitus in India) and CINDI2 (cardiovascular risk • Though surgical interventions are crucial for cataract management, in
factors, micro and macrovascular complications at diagnosis in patients most of the patients, particularly those with complicated cataracts,
vision may not be restored. These patients eventually develop corneal 25.7% had DR of some grade based upon a standard fundus camera
decompensation, glaucoma, and optic atrophy443. Because the progno- examination and the UK- based DR grading protocol (Spectra™ soft-
sis of the retina is poor, especially in the presence of mature cataract, the ware). Majority of the patients were satisfied with the screening and
panel suggested that it is crucial to educate the patient about the guarded found it reliable and acceptable to undertake examination under pupil
prognosis for regaining vision after IOL surgery. dilation; 67.3% were willing to undergo nonmydriatic fundus camera
examination again. Participants found digital retinal screening to be reli-
Evidence able and satisfactory. Telemedicine can be a vital tool, supporting eye
Though evidence from past studies suggests that the prevalence of DR is care professionals and allowing for faster and more comfortable DR
low in Indians compared to other ethnic groups, emerging data indicate screening456.
significant increase in prevalence of retinopathy in South Asians com-
pared to Caucasians444. Data from a population- based study (CURES) NEUROPATHY
indicate that the overall prevalence of DR in urban south Indian popula- Recommendations
tion was 17.6%, with higher prevalence among men than in women
(21.3% vs. 14.6%; p<0.0001) and among subjects with proteinuria Recommended Care
(p=0.002)445. Similarly, prevalence of DR in western India was found
to be 33.9%446. Data from a recent population-based cross-sectional study • All patients with T2DM should be assessed for diabetic neuropathy at the time of
suggests that one of 10 individuals in rural South India, above the age of initial diagnosis and annually.
• Diagnose sensorimotor nerve damage by history and examination (10 g
40 years, had evidence of DR447. A meta-analysis of seven studies from monofilament with or without temperature, non-traumatic pin-prick, vibration
India found 14.9% of known diabetes patients aged ≥30 years and 18.1% [128 Hz tuning fork], ankle reflexes), and/or simple quantitative testing (e. g.
among those aged ≥50 years had DR. Furthermore, no linear trend was biothesiometer vibration perception). Use serum B12, thyroid function tests,
observed between age and the proportion with DR448. Duration of diabe- creatinine/urea, alcohol abuse, and medication history to exclude other causes.
• Diabetic Neuropathy Symptom Score (NSS) and Neuropathy Disability Score
tes, HbA1c, male gender, macro-albuminuria, and insulin therapy were
(NDS) in T2DM population has been found to be a useful resource in evaluating
strongly associated with increased risk of DR among South Indians449,450. diabetic sensorimotor polyneuropathy as an important bed side tool.
Moreover, the risk of nephropathy (OR: 5.3, p<0.0001) and neuropathy • Diagnose symptomatic (painful) diabetic neuropathy by excluding other possible
(OR: 2.9, p<0.0001) was significantly higher among T2DM patients with causes of the symptoms. Manage by stabilizing blood glucose control, and
DR compared to those without DR451,452. After adjusting for age, gender, treatment with tricyclic antidepressants if simple analgesia is not successful. If a
one-month trial of tricyclic therapy is not successful, further treatment options
HbA1c, SBP, serum triglycerides, and duration of diabetes, DR was
include pregabalin/gabapentin and duloxetine, then tramadol and oxycodone.
significantly associated with nephropathy (p=0.005) than with neuropa- • Weight gain and lifestyle measures need reinforcement with the use of
thy451. Another study showed HbA1c, BMI, duration of diabetes, antidepressants and gabapentin, and pregabalin.
microalbuminuria and peripheral neuropathy are contributing factors in • Further management requires typically referral to a pain control team. Be aware
the degree of retinopathy (p=0.001). This correlation was explained by of the psychological impact of continuing symptoms, particularly if sleep is
disturbed. In patients with diabetic neuropathy and co-morbid depression,
common mechanisms involved in tissue damage by all these factors. anxiety, and sleep loss, duloxetine should be preferred.
Microalbuminuria was positively correlated with retinopathy in T2DM • A visual record of a simple graphic tool to measure response to therapy must be
patients and may be a marker for the risk of severe and proliferative mandated, which will save patients from over/unnecessary treatment.
retinopathy development. Microalbuminuria was associated cross- • Tools, e. g., pain scale should be encouraged in clinical practice.
• Diagnose erectile dysfunction by history (including medication history), exclusion
sectionally with the presence of retinopathy in patients with T2DM.
of endocrine conditions (measure prolactin and testosterone), and a trial of a
This study suggests that microalbuminuria may be a marker for the risk phosphodiesterase type-5 (PDE5) inhibitor (where not contraindicated by nitrate
of proliferative retinopathy development453. Recent studies have also therapy). Consider other approaches such as intra-urethral or intracavernosal drugs
started shedding light on the association of dyslipidemia with DR. 454 and sexual & relationship counselling, where PDE5 inhibitors fail or cannot be
used.
• Discourage the use of alternative medicines as they can cause further complications.
Implementations
• Diagnose gastroparesis by history, trial of a prokinetic drug (metoclopramide,
A sufficient number of trained general ophthalmologists and general phy- domperidone), and if troublesome, by gastric emptying studies.
sicians are required to develop an integrated DR model that facilitates • Diagnose CV autonomic neuropathy by resting heart rate and heart rate response to
early detection and create awareness of DR. Medical camps should be provocation tests (lying-standing, Valsalva, deep breathing), and by lying and
conducted for screening of diabetes and retinopathy, which will help to standing BP. Inform anaesthetists, when relevant, where this is present.
• Every patient must undergo a simple assessment e. g. questionnaire-based assessment
identify people at risk of sight-threatening DR and initiate treatment in- for depression.
cluding laser photocoagulation or vitreous surgery. Mobile vans with a
fundus camera or other low-cost tools that can be used in remote rural
areas should also be explored. However, successful program implemen-
tation requires a team approach involving both administrative and volun-
tary organizations.
Telemedicine-based DR screening costs less ($10 vs $25) than conven-
tional retinal examination and the telemedicine-based digital retinal im-
aging examination has the potential to provide an alternative method with
greater convenience and access for remote and indigent populations. This Limited Care
cost-effective technology-driven model would prevent the screening • Screen and diagnose sensorimotor nerve damage by history of symptoms, and
costs, help in the early detection of DR, and prevent a common cause sensory assessment by 10g monofilament or tuning fork with/without non-
of blindness. Telemedicine should be encouraged to improve access and traumatic disposable pin-prick.
increase compliance with annual evaluation, at a low cost for patients • NSS and NDS in T2DM population has been found to be a useful resource in
with diabetes.455 Tele-diabetes shares some of the same attributes as evaluating diabetic sensorimotor polyneuropathy as an important bedside tool.
• Manage symptomatic (painful) diabetic neuropathy by excluding other causes,
telemonitoring for other chronic conditions, such as congestive heart stabilizing glycemic control, and treatment with tricyclic antidepressants if simple
failure, stroke, and chronic obstructive pulmonary disease. In a pilot study analgesia is unsuccessful. Opiate analgesia may be necessary as locally available.
conducted in Hungary on patients with diabetes, 30% of the patients had • Assess erectile dysfunction by history and examination and consider possible
never participated in any ophthalmological screening. In comparison, contributions of other medication or disease.
Background neuropathy, gabapentin monotherapy was efficacious for treating pain

Neuropathy is among the most common life-threatening complication of and sleep interference associated with diabetic peripheral neuropathy
diabetes that involves both peripheral and autonomic nerves, affecting up along with positive effects on mood and quality of life485.
to half of all diabetic patients. Hyperglycemia-induced polyol pathway, injury • Duloxetine and pregabalin were approved by the USFDA in 2004 and
from AGEs, and enhanced oxidative stress have been implicated in its tapentadol extended release were approved in 2012 for the treatment of
pathogenesis457,458Peripheral neuropathy in diabetes appears in several forms painful diabetic neuropathy (PDN)486.
depending on the site, manifesting as sensory, focal/multifocal, and autonom- • Pregabalin is a potent gabapentinoid used in the management of PDN.
ic neuropathies.459 Diabetic neuropathy has resulted in more than 80% of Several double-blind placebo-controlled trials have reported the dose
amputations after foot ulceration or injury. It is among the most common, dependent (600 mg/daily) efficacy of pregabalin; however, several side
expensive, and disabling complications of diabetes, affecting approximately effects, including mood disturbance, ankle oedema and sedation also
30% of hospitalized patients with diabetes and 25% of patients with diabetes have been reported487–489.
in the community460. About 30% of patients with known or newly diagnosed • Both duloxetine and pregabalin are effective; however, a significant
diabetes suffer from diabetic neuropathy461,462. In the cross-sectional survey improvement in QoL of patients was obtained by duloxetine with com-
of Indian patients with T2DM in CINDI and CINDI2 studies, diabetic neu- paratively mild increase in the price490.
ropathy was prevalent in 13.15% and 13.2% of patients, respectively463,464. • Duloxetine is a selective inhibitor of the reuptake of both 5-
As per the Toronto Consensus Panel, diabetic polyneuropathy is a “symmet- hydroxytryptamine and norepinephrine 491,492 . Results from
rical, length-dependent sensorimotor polyneuropathy attributable to metabol- randomized-controlled clinical trials reveal that duloxetine provides
ic and micro-vessel alterations as a result of chronic hyperglycemia exposure significantly more diabetic neuropathic pain relief than either placebo
and cardiovascular risk covariates”465. The most common form of diabetic or routine care, with higher safety and tolerability493–495. Moreover, a
neuropathy is the distal symmetrical polyneuropathy that involves both tibial recent Cochrane collaboration review including data from eight studies
and sural nerves466. The presence of neuropathy is associated with significant and 2728 participants reported that 60 mg and 120 mg daily doses of
morbidity, including recurrent foot infection and ulcers, impotence in men duloxetine were efficacious. Still, lower doses were not associated with
with diabetes, and sudden death in individuals with CV autonomic neurop- improvement in the PDN management496.
athy.467–470 Neuropathic pain in patients with diabetes is commonly encoun- • Tapentadol, an opioid analgesic, may act via opioid spinal-supraspinal
tered in clinical practice466,471. The present recommendations provide in- synergy, as well as intrinsic spinally mediated μ-opioid receptor agonist-
sights into the management aspects of diabetic neuropathy while exploring norepinephrine reuptake inhibitor effect497. The efficacy and safety of
newer therapeutic options that have emerged in recent years. tapentadol were also published in several clinical trials498,499. Tramadol
may also be used for pain management. However, there is only modest
Rationale and Evidence information about the use of tramadol in neuropathic pain, primarily from
Detection of sensorimotor polyneuropathy small, largely inadequate studies500. Further, a fixed-dose combination of
• Though nerve conduction studies are powerful tools for identifying cases tramadol/paracetamol might be a useful pharmacological option for
of diabetic neuropathy472, NSS473 and NDS474 in T2DM patients were chronic pain management, particularly in elderly patients501.
found to be a valuable resource for evaluating diabetic sensorimotor • Neuropathic pain can be severe, impact quality of life, limit mobility,
polyneuropathy as a bedside tool475. A cross-sectional study in T2DM and contribute to depression and social dysfunction502. Management of
patients that examined the nerve conduction velocities of motor and sen- underlying depression is a must to improve QoL. Tricyclic antidepres-
sory nerves, using NSS and NDS in patients with clinically detectable sants, venlafaxine, carbamazepine, and topical capsaicin, although not
neuropathy showed significant electrophysiological changes with the du- approved for the treatment of painful diabetic neuropathy, may be effec-
ration of T2DM475. Similar results were observed in another study where tive and considered for the treatment503–506.
NSS and NDS helped in prompt evaluation of diabetic sensorimotor • Capsaicin has been used with some success in the treatment of patients
polyneuropathy and in diagnosing subclinical cases476–478. A study that with PDN. It binds to the receptor that opens the TRPV1 causing sodium
validated the use of NSS and NDS for clinical diagnosis of peripheral and calcium influx and substance P release occurs, Repeated TRPV1
neuropathy in middle aged 855 T2DM patients showed that NSS and exposure to capsaicin causes substance P depletion and TRPV1 desensi-
NDS can detect diabetic neuropathy with a sensitivity of 71.1% and tization and defunctionalization507.
specificity of 90% and was found to be simple, acceptable, reproducible • Lidocaine blocks the voltage-gated sodium channels and stabilizes the
and validated method for early diagnosis of diabetic neuropathy479,480. neuronal membrane potential, reducing ectopic discharges and raising pe-
• The panel emphasized on neurological examination using NSS and ripheral ectopic discharge threshold, causing reduced pain transduction508.
NDS as it is important bed-side tool and a useful resource in evaluating
diabetic sensorimotor polyneuropathy.
• Type 2 diabetes patients with abnormal ABI were predicted to have a
27% increased odds ratio of CAD outcome and 80% in the presence of
nephropathy. Thus, as part of comprehensive diabetes care, albuminuria
screening and ABI measurement are suggested.481
• Recent studies have also shed light on the severe microvascular com-
plications and surrogate markers to detect the same.482–484
Management of diabetic neuropathy [Figure]

Diabetic peripheral neuropathic pain can be managed with several classes
of drugs including tricyclic antidepressants, anticonvulsants, serotonin-
norepinephrine reuptake inhibitors, opiates and opiate-like substances, Figure 7: Management algorithm for neuropathy. OADs: Oral antidia-
and topical medications. betics; SNRIs: Serotonin-norepinephrine reuptake inhibitors; SSRIs:
Selective serotonin reuptake inhibitors
• Tricyclic antidepressants are recommended as first-line therapy for dia-
betic peripheral neuropathic pain in appropriate patients. Implementation
• Gabapentin is an anticonvulsant structurally related to γ-aminobutyric Appropriate protocols should be developed for sensory testing and may
acid (GABA), a neurotransmitter that plays a role in pain transmission include formal assessment using the NSS and NDS. Recommended med-
and modulation. In patients with a history of pain attributed to diabetic ications should be available according to the level of resources. Medical
teams need to remain trained in the diverse manifestations of autonomic Limited Care
neuropathy467.
• Check annually for proteinuria in an early morning urine sample (or a
random sample) using a dipstick. If the test is positive exclude UTIs by
DIABETIC KIDNEY DISEASE microscopy (and culture if possible).
Recommendations • Measure serum creatinine and calculate eGFR annually.
• A simple, inexpensive screening procedure for urinary protein excretion which can
be used as a diagnostic test in outpatient has been reported in the Indian
Recommended Care
population. Estimated proteinuria is useful in the serial evaluation of kidney
• Kidney function should be assessed at diagnosis and annually by: function.
- Urine test for albuminuria • Manage those with proteinuria as follows:
- Measurement of serum creatinine and calculation of eGFR - Consider use of ACE inhibitors or ARBs and SGLT2 inhibitors unless
• Urinary albumin to creatinine ratio (ACR) measurement in an early morning first contraindicated or issues with tolerability
void (mid-stream) spot specimen is the preferred method for assessment of - Aim for BP ≤130/80 mm Hg using any BP lowering medication and control of salt
microalbuminuria/proteinuria. Where a first void specimen is not possible or intake [Table]
practical, a random spot urine specimen is acceptable. ACR can be measured in the - Aim to achieve targets for blood glucose control
laboratory or at site-of-care. - Aim to improve lipid profile using available medications
• Control hyperglycemia, exclude urinary or systemic infections, or pyrexia and avoid - Check proteinuria status annually
strenuous exercise before testing for albuminuria. - Measure serum creatinine and calculate eGFR annually
- If ACR is raised (microalbuminuria) i.e. ACR >30 mg/g creatinine, repeat ACR
twice over the following four months:
Background
Previously known as diabetic nephropathy, DKD is defined as diabetes
with albuminuria (ratio of urine albumin-to- creatinine ≥30 mg/g), im-
paired glomerular filtration rate (<60 mL/min/1.73 m2), or both and is
» Microalbuminuria is confirmed if ACR is elevated in two out of three tests, now recognized as the strongest predictor of mortality in patients with
in the absence of infection or overt proteinuria diabetes509. It is a leading cause of ESRD affecting ∼20–30% diabetes
» If both repeat tests are not raised, check again annually
patients, and is associated with increased CV mortality510. It affects 10–
» An ACR >300 mg/g indicates macroalbuminuria
• DKD is diagnosed on the basis of a raised urine albumin/protein or a reduced eGFR 40% of T2DM patients who eventually suffer from kidney failure511,512.
(<60 mL/min/1.73 m2) calculated from the Chronic Kidney Disease Epidemiology In the cross-sectional survey of Indian patients with T2DM in CINDI and
Collaboration (CKD-EPI) equation. CKD-EPI is the preferred formula. CINDI2 studies diabetic nephropathy was prevalent in 1.06% and 0.9%
• The Modification of Diet in Renal Disease (MDRD) formula for calculation of eGFR of patients respectively513,514. The cost of treatment for advanced DKD is
is not validated above 70 years of age and in Indian patients.
• For patients <18 years of age (including infants, toddlers, children, and teens), the
substantial. Less than 10% of ESRD patients have access to any kind of
Bedside Schwartz equation should be used. renal replacement therapy515,516. Thus, in a country with limited re-
• Individuals with DKD should be managed as follows: sources, it becomes appropriate to direct efforts toward the prevention
- Identified high-risk individuals (hypertensives, duration of diabetes >3-5 years, of DKD rather than the treatment.
family history of nephropathy/HF/ASCVD) must get preference for SGLT2
inhibitors for glycemic management if feasible and accepted by patients (eGFR
>30 mL/min/1.73 m2)
Pathophysiology of diabetic kidney disease
- Use angiotensin converting enzyme (ACE)-inhibitors or angiotensin receptor The pathophysiological mechanisms of DKD are complex and are often
blockers (ARBs) in individuals with micro-or macro-albuminuria, titrated to the evident by intrarenal hypertension, compromised GFR and
maximum tolerated dose microalbuminuria. Microalbuminuria, is the first and most critical mani-
- Intensify management of BP (target ≤130/80 mm Hg) using BP lowering
festation of diabetic nephropathy, which when progressed to overt albu-
medications and dietary modification (low salt and reduced protein intake)
- Intensify management of blood glucose minuria (increased albumin levels in the urine) indicates severe renal
- Monitor ACR, eGFR and serum potassium dysfunction culminating to renal failure 517 . The presence of
- Advise daily limiting protein intake to 1 g/kg of high biological value protein. In microalbuminuria is a powerful marker of cardiovascular disease and
those with advancing CKD, restrict to 0.8 g/kg daily with advice for caution in all-cause mortality518. Thus, the presence of diabetes, particularly accom-
patients consuming a non-vegetarian diet
• Intensify other renal and CV protection measures
panied by microalbuminuria, is most often considered a warning signal
• Assessment and management of anemia and bone disease and appropriate vaccination for CV risks in patients with diabetes.
• Smoking leads to progression to end-stage renal disease (ESRD) in diabetes, so DKD is characterized by a constellation of histopathological changes
patients must be counselled to quit smoking beginning from glomerular hyperfiltration causing glomerular basement
• Consider referral to nephrologists when there is uncertainty about the etiology of membrane thickening, progressive accumulation of extracellular matrix
kidney disease, complex management issues (stress, obesity, high uric acid, UTIs,
anemia for timely use of Erythropoietin analogues, BP to targets, Nocturnal BP
in glomerular mesangium and tubulointerstitium, causing mesangial ex-
control stressed) pansion and Kimmelstiel–Wilson nodules (an aggregation of mesangial
• Agree to a referral criterion for specialist renal care between local diabetes specialists cells and mesangial matrix), arterial hyalinosis, and tubulointerstitial
and nephrologists. Referral criteria might include changes [Figure 9]. Additionally, podocyte dropout is also a critical factor
- eGFR<30 mL/min/1.73 m2, progressive deterioration of kidney function,
for DKD development. Podocytes are known to distort and change their
persistent proteinuria, biochemical or fluid retention problems or difficult
diagnosis (to rule out non-diabetic renal disease where fundus is normal and no size and shape to accommodate or cover the openings created by the
proteinuria). basement membrane thickening causing them to shift or dropout.
• Rule out non-diabetic kidney disease in patients with early onset of nephropathy (<5
years), absence of retinopathy, heavy proteinuria, presence of active urinary
sediments or unexplained rapid decline in eGFR.
EPE was found to be useful in the serial evaluation of kidney function in

Indian patients with diabetes526,527. Moreover, EPE is a simple and
inexpensive screening procedure for urinary protein excretion, which
can be used as a diagnostic test in outpatient wards, particularly in
developing countries like India.
• As EPE is an inexpensive screening procedure to assess kidney function,
the panel recommended it for use in the Indian population who are at
risk of diabetic nephropathy.
• Screening of microalbuminuria and estimating glycated albumin can help in
the clinical management of diabetic nephropathy528. Screening for albumin-
uria by measuring urine albumin concentration or estimating ACR is ac-
ceptable in the Asian population529. However, evidence suggests that vig-
orous exercise even for short periods (15–20 min) leads to ACR above the
microalbuminuria threshold even in healthy participants530,531.
• Based on evidence, the panel suggested that physicians should ask about
recent vigorous exercise and avoid measuring urine albumin excretion
for at least 24 h in the presence of same.
• Microalbuminuria shows a strong association with increased CVD risk
in diabetic patients in Indian population532–534.
Figure 8: Pathophysiology pathways in diabetic kidney disease. AGEs: • A recent cross-sectional study in diabetic nephropathy patients showed a
Advanced glycation end products; PKC-DAG: Protein kinase C- positive correlation between eGFR and cortical renal thickness. Cortical
diacylglycerol;RAAS: Renin-angiotensin-aldosterone-system; VEGF: renal thickness was a better predictor of renal function than bipolar renal
Vascular endothelial growth factor length.535
In India, with an increase in the prevalence of diabetes, it becomes im- Management of hyperglycemia in patients with diabetic kidney disease
perative to evolve definite guidelines for the detection of diabetic ne- In patients with DKD, when selecting and dosing glucose-lowering
phropathy and suggest practical clinical recommendations to combat it. drugs, renal function has to be assessed and periodically monitored during
Improving glycemic control, aggressive antihypertensive treatment, and treatment to detect changes that may affect drug metabolism and excre-
the use of ACE inhibitors or ARBs will slow down the rate of progression tion. While mild renal insufficiency can be treated with most OADs,
of nephropathy519,520. In addition, protein restriction and other treatment patients with DKD stage 3-5, most often require treatment adjustments
modalities such as phosphate lowering may have benefits in selected according to the degree of renal insufficiency.
patients521. Careful consideration should be given to normoalbuminuric Combinations of therapies are available for the management of hypergly-
kidney disease in patients with T2DM. Although the serum creatinine is cemia in patients with type 2 diabetes. Metformin is a first-line agent in all
usually normal, most normoalbuminuric patients with DKD have an patients, including patients with DKD. Second-generation
eGFR <60 mL/min/1.73 m2 per the MDRD formula. However, as expect- sulphonylureas are also commonly used. Although, the reduction in
ed, because of normoalbuminuria and other favorable characteristics, HbA1c is modest with an average between 0.5-1.0%, DPP-4 inhibitors
their risk for DKD progression or death is lower.522 can be safely used at the appropriate dose in DKD. SGLT2 inhibitors and
DPP-4 inhibitors are responsible choices in moderate to severe cases of
DKD [Table 14].
Identification and monitoring and diabetic kidney disease: Persistent Oral antidiabetics that exert renoprotection
microalbuminuria is the earliest sign of diabetic nephropathy or DKD. • Evidence suggests that two oral hyperglycemic agents DPP-4 inhibi-
The diagnostic reference standard for defining microalbuminuria is the tors536 and SGLT2 inhibitors, exert renoprotective effects in patients
detection of 30 to 300 mg of albumin in a 24-h urine sample and is the with diabetes. SGLT2 inhibitors are indicated to improve glycemic
first-line annual screening test for most persons with diabetes. It is rec- control in adults with T2DM by reducing the reabsorption of filtered
ommended that once a screening test detects microalbuminuria, it should glucose. They can also lower the renal threshold for glucose, thereby
be confirmed with additional spot urine tests over the next three to six increasing urinary glucose excretion.
months. The Kidney Disease Outcomes Quality Initiative (KDOQI)- • While these medications have been used safely in patients with Stage 3
Clinical Practice Guidelines and Clinical Practice Recommendations for DKD (eGFR down <30 mL/min), the glycemic reduction response to
Diabetes and Chronic Kidney Disease by the National Kidney the SGLT2 inhibitors declines with decreasing kidney function, as a
Foundation (NKF), recommend that patients with diabetes should be decrease in eGFR results in a decrease in urinary glucose excretion.
screened annually for CKD: 5 years after the diagnosis of type 1 diabetes • Canagliflozin has been approved for use in patients with eGFR>45 mL/
and from onset/diagnosis of type 2 diabetes. The presence of albuminuria min/1.73 m2, with a dose limited to 100 mg once daily in patients with
must be evaluated based on the UAE concentration or Urinary albumin- eGFR 45≤60 mL/min/1.73m2. Empagliflozin can also be used in pa-
to-creatinine ratio (UACR) in untimed (spot) urine specimens and by tients with an eGFR down to 45 mL/min/1.73 m2, while dapagliflozin is
estimating the glomerular filtration rate from serum creatinine measure- approved in patients with an eGFR down ≥60 mL/min/1.73 m2. Regular
ments by using prediction equations523,524. The ADA recommends iden- assessment of renal function is recommended with the use of any of
tifying and monitoring DKD based upon assessments of kidney function these SGLT2 inhibitors.
with an estimated GFR (eGFR), 60 L/min/1.73m2, or kidney damage by • Recently completed CREDENCE study reported that at a median
estimation of albuminuria 30 mg/g creatinine along with annual screening follow-up of 2.62 years, the risk of kidney failure and cardiovascular
for microalbuminuria. Clinical recommendations by the ADA for DKD events was lower in the canagliflozin group than in the placebo
screening also suggest that persons with type 1 or 2 diabetes and group537. In the Canagliflozin Cardiovascular Assessment Study
microalbuminuria should continue to be tested for albuminuria annually (CANVAS) Program, canagliflozin treatment was associated with a
to monitor disease progression and response to therapy525. reduced risk of sustained loss of kidney function, attenuated eGFR
• Estimated Protein Excretion (EPE) is a method of estimating ACR in a decline, and a reduction in albuminuria. These encouraging results
random urine sample to assess renal function in patients with diabetes.
suggest that canagliflozin exerts renoprotective effect in patients with Referral to specialist
T2DM538. The panel endorsed IDF recommendation on referral criteria; however, it
• The EMPA-REG OUTCOME trial evaluated the non-inferior cardio- was suggested that, most of the patients at this stage of diabetic nephrop-
vascular safety of empagliflozin in high- CV-risk T2D patients with an athy require a specialist care which may not be available at primary care
estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73 or single physician center. Hence, local diabetes specialists should refer
m2. Empagliflozin reduced the rate of new onset or worsening nephrop- the patient to specialist renal care center/nephrologist. Likewise, nephrol-
athy, which were defined as new-onset microalbuminuria, doubling of ogists should refer patients to specialist renal care if the patient presents
creatinine, and eGFR ≤ 45 mL/min/1.73 m2, initiation of renal replace- with following condition:
ment therapy, and death due to renal disease (hazard ratio [HR]: 0.61,
95% confidence interval [CI]: 0.53–0.70; p < 0.0001)539. - eGFR<30 mL/min/1.73 m2
• Results of the DECLARE–TIMI 58 cardiovascular outcomes trial sug- - progressive deterioration of kidney function
gest that, in patients with T2DM, Dapagliflozin prevented and reduce - persistent proteinuria, biochemical or fluid retention problems or
the progression of renal disease540. - difficulty in diagnosis (to rule out non diabetic renal disease where
• The DAPA-CKD trial concluded that among patients with chronic fundus is normal and proteinuria is not present).
kidney disease, regardless of the presence or absence of diabetes,
the risk of a composite of a sustained decline in the estimated GFR Table 15: Stratifying target blood pressure as per clinical condition
of at least 50%, end-stage kidney disease, or death from renal or
cardiovascular causes was significantly lower with dapagliflozin Guideline Recommendation
than with placebo. 541
• The EMPA-Kidney study in an ongoing randomised controlled trial. The <140/90 mmHg is recommended to decrease CVD mortality
and slow down CKD progression
primary aim of the study is to investigate the effect of empagliflozin on
Lesser targets such as <130/80 mmHg might be considered in
kidney disease progression or cardiovascular death versus placebo on top of ADA individuals with albuminuria and at increased risk of CVD and
standard of care in patients with pre-existing chronic kidney disease. 542 2019[451] CKD progression
While achieving <130 mmHg SBP target, especially in old people,
Protein restriction care should be taken to avoid DBP levels
• IDF recommends limiting protein intake to 1 g/kg body weight daily <60-70 mmHg
among individuals with DKD, if they are found proteinuric. Similarly, In DKD patients, not requiring dialysis, with UAE <30 mg/day and
ADA recommends protein intake should be 0.8 g/kg/body weight/day office BP consistently below 140/90 mm Hg, a target of ≤140/90
in patients with DKD543. In the Indian context, the source of protein is KDIGO mmHg is recommended
2012[452] In DKD patients, not requiring dialysis, with UAE >30 mg/day and
mainly from vegetable and animal oils and daily protein consumption is office BP consistently >130/80 mm Hg, a target of ≤130/80 mmHg
about 0.6–0.8 g/kg body weight.544 Furthermore, protein content in is recommended
non-vegetarian diet was found to be higher when compared to the veg-
ADA: American Diabetes Association, BP: Blood pressure, CKD: Chronic kidney disease,
etarian diet.545 In addition, evidence suggests that animal protein may CV: Cardiovascular, CVD: CV disease, DKD: Diabetic kidney disease, SBP: Systolic BP,
aggravate the risk of diabetes546. Therefore the panel emphasized on DBP: Diastolic BP, UAE: Urinary albumin excretion
protein restriction and avoiding extra protein intake, particularly in non-
vegetarians with nephropathy.
Indian evidence
Smoking • Prevalence of microalbuminuria is strongly associated with age, DBP,
• Smoking is associated with hyperglycemia, dyslipidemia and decline in HbA1c, FPG and duration of diabetes552,553.
GFR which leads to the progression of ESRD in patients with diabe- • A positive co-relation between urine albumin excretion rate and eGFR
tes547,548. Smoking tends to induce albuminuria and abnormal renal <60 mL/min/1.73m2 was observed indicating that these two parameters
function through formation of advanced glycated end products provide a complimentary benefit in management of CKD554.
(AGEs), which are responsible for advanced vascular permeability and • Vitamin D deficiency can have significant impact on albuminuria. Therefore
kidney damage.549 A recent systematic review reported that consump- supplementation with calcitriol should be considered in these patients as it
tion of ≥15 packs of cigarettes/year increases the risk of progression of has been shown to provide beneficial effects on microalbuminuria555.
DKD550. Moreover, data from a recent study in India suggests that
compared to non-smokers the prevalence of microalbuminuria in Implementation
smokers was 4-fold higher551. Management of DKD requires access to healthcare professionals, labora-
• The panel opined that patients must be counselled against tobacco use and tory for ACR and creatinine estimations, and the availability of multiple
encouraged to quit smoking to reduce the risk of progression to ESRD. blood-pressure-lowering medications, in particular renin-angiotensin sys-
tem blockers.
Table 16: Dose adjustment for oral antidiabetics agents for patients CHRONIC COMPLICATIONS 2: DIABETIC FOOT AND
with diabetic kidney disease PERIPHERAL ARTERIAL DISEASE
Class Dose adjustments Recommendations
Metformin Metformin can be used till to GFR 30

Recommended Care
GFR ≥45-59: use caution with dose and follow renal
function • Assess feet of patients with diabetes at every visit for lesions requiring active
GFR ≥30-44: max dose 1000 mg/day or use 50% dose treatment and for risk factors for ulcer and amputation:
reduction. Follow renal function every three months GFR: - History of previous foot ulceration or amputation, symptoms of peripheral
<30: avoid use arterial disease (PAD), physical or visual difficulty in self-foot-care
- Foot deformity (hammer or clawed toes, bone prominences), visual evidence of
Second-generation Glipizide: GFR <30: Use with caution
neuropathy (dry skin, dilated veins) or incipient ischemia, callus, nail deformity,
SU Glimepiride: GFR <60: Use or damage. Patient footwear should also be assessed
with caution; <30: Avoid use
- Detection of neuropathy by 10 g Semmes Weinstein monofilament (or 128 Hz
Glyburide: Avoid use
tuning fork); a biothesiometer (to assess vibration perception threshold) is an
Gliclazide-upto GFR 30: No dose adjustment; <30: Low
option for quantitative assessment (cut-off point for ulcer risk >25 volts) and
dose preferred
non-traumatic pin-prick.
TZD No dose adjustment - Michigan Neuropathy screening instrument is a useful, easy-to-use
epidemiological tool to assess neuropathy in a patient with diabetes.
Alpha-glucosidase Acarbose: Serum creatinine >2 mg/dL: Avoid use - Palpation of foot pulses (dorsalis pedis and posterior tibial). Doppler ultrasound
Inhibitors Miglitol: GFR <25 or serum creatinine >2 mg/dL: Avoid examination or ankle: brachial pressure (ABI) ratio (<0.9 for occlusive vascular
use disease) may be used where pulses are diminished to quantify the abnormality.
• Discuss the reasons for foot review with each patient with diabetes, as part of the
DPP-4 inhibitor Sitagliptin: GFR≥50: 100 mg foot-care educational process.
daily; GFR 30-49: 50 mg daily • Must completely refrain from walking barefoot, including visiting religious places.
GFR <30: 25 mg daily • Timely screening and early detection of diabetic neuropathy may help prevent the
Saxagliptin: GFR >50: 2.5 or 5 progression to diabetic foot.
mg daily; GFR ≤50: 2.5 mg daily • Agree upon a foot-care plan based on the findings of an annual foot review
Linagliptin: No dose adjustment with each person with diabetes. Assess and provide necessary foot-care
Alogliptin: GFR >60: 25 mg daily; GFR 30-59: 12.5 mg education according to individual needs and risks of ulcer and amputation.
daily; GFR <30: 6.25 mg daily • F18PET/CT (labeled WBC) may be considered (if available) to confirm osteomyelitis
Tenaligliptin 20 mg/day - No dose adjustment in the complicated diabetic foot; if MRI is contraindicated because of CKD.
• Classify and manage according to risk classification level based on findings of foot
SGLT2i Canagliflozin: GFR 45-<60: Maximum dose 100 assessment.
mg OD; GFR<45: avoid use Dapagliflozin541: GFR • People with foot ulceration or infection require the following management:
<60: Avoid use
- Pressure offloading
Empagliflozin542: GFR <45: Avoid use
- Refer to a multidisciplinary foot-care team within 24 h for:
Mineralocorticoid MRA- Finerenone556 : full dose : 20-mg daily. » Appropriate wound management, dressings, and debridement as indicated
Receptor eGFR: 25–60 ml/min per 1.73 m2 or serum » Infections should be classified as mild (superficial with minimal cellulitis),
Antagonists potassium 4.8–5 mEq/L,10 mg daily moderate (deeper than skin or more extensive cellulitis), or severe
(MRA) (accompanied by systemic signs of sepsis). Consideration of systemic antibiotic
therapy (often longer term) for extensive cellulitis or bone infection as
GFR: Glomerular filteration rate, SU: Sulfonylureas, OD: Once daily, TZD:
Thiazolidinedione, DPP-4: Dipeptidyl peptidase, SGLT2i: Sodium-glucose
co-transporter 2 inhibitors
indicated. Risk classification level Management

- First-line medications: generic penicillin, cephalosporins, macrolides,
clindamycin and/or metronidazole, as indicated No added risk: Provide structured foot-care education and annual
- Second-line medications: amino-quinolones co-amoxicillin, imipenem. No risk factors; no previous history review.
- Medical treatment may be considered as an adjunct after TCC. of foot ulcer or amputation
- Methylprednisolone and bisphosphonates have not been shown to
reduce the time to remission. At risk: • Foot-care team to regularly review every 6
- Rivoraxaban for PAD also has promising outcomes in diabetic foot One risk factor; no previous history months.
patients of foot ulcer or amputation • At each review:
» Probing to bone, radiology and scans, magnetic resonance imaging and biopsy - Inspect both feet - ensure provision of
were indicated for suspected osteomyelitis local management as indicated
» Reduce weight bearing, relief of pressure (walking with crutches, rest) - Educate patient to wash feet daily
offloading and optimal pressure distribution (casting, if indicated) (with careful drying, particularly
» Investigation and treatment (referral) for vascular insufficiency between the toes), use emollients to
» Specialist therapeutic footwear and orthotic care (e. g. insoles) and lubricate dry skin, cut toe nails straight
individualized discussion of prevention of recurrence, when an ulcer has healed across, and avoid using chemical
» Optimal blood glucose control agents or plasters or any other
• Patients with foot complications, including DFU have an increased risk of mortality technique to remove callus or corns
and need close monitoring for cardiovascular events. - Evaluate footwear - provide appropriate
• Tc 99m uptake scan may be considered for the diagnosis of Charcot, if MRI is advice
contraindicated. - Enhance foot-care education
• Amputation should not be considered unless:
High risk: • Foot-care team to frequently review every
- A detailed vascular evaluation has been performed by the vascular team 3-6 months.
≥2 risk factors; previous ulcer or
- Ischemic rest pain cannot be managed by analgesia or revascularization • Educate patient to self-monitor foot skin
amputation (very high risk)
- A life-threatening foot infection cannot be treated by other measures temperatures once per day to identify any
- A non-healing ulcer is accompanied by a higher burden of disease that would early signs of foot inflammation to prevent a
result in amputation. first or recurrent plantar foot ulcer.
- Management of Charcot’s foot will include • At each review:
• Non-surgical treatment: offloading (casting), walking in a walking boot, use - Inspect both feet - ensure the provision
of Charcot Restraint Orthotic Walker (CROW) of local management as indicated
• Surgical treatment: Surgery is recommended for those patients who have - Evaluate footwear - provide advice and
severe ankle and foot deformities that are unstable and at high risk of specialist insoles and shoes if indicated
developing a foot ulcer. In addition, if the deformity makes braces and - Consider the need for vascular
orthotics challenging to use, surgery may be indicated. After surgery, the assessment or referral, if indicated
patient will have to avoid putting full weight on the Charcot’s foot for an - Evaluate and ensure appropriate
extended period. provision of intensified foot-care
• Danosumab may be considered along with TCC to reduce the risk of education
fractures in acute Charcot Foot. However, Teriparatide has not been shown
to reduce time to remission or fracture risk.
• COVID-19 and its impact
- COVID-19 is associated with an increased risk of thrombotic complications
including the peripheral ischemic foot. It needs heightened screening with ABI
in patients with a history of COVID-19. Limited Care
• Diabetic patients with the risk or history of stroke:
- Pioglitazone may be effective for secondary prevention in patients with • Risk assessment and classification: Similar to ‘recommended care’ but with
stroke/transient ischemic attack. sensory assessment by 10 g monofilament or tuning fork, with or without non-
traumatic disposable pin-prick only, and peripheral circulation assessment by
palpation of pedal pulses.
• NSS and NDS in T2DM population have been found to be a useful resource
and an essential bed-side tool in evaluating diabetic sensorimotor
polyneuropathy.
• Classification of infection: Similar to ‘recommended care’, but antibiotic
therapy would be with generic penicillin, quinolones, macrolides and/or
metronidazole, given intravenously for deep tissue infections adjusted by
response or culture results.
• Vascular referral would be according to findings and local revascularization
facilities.
Background
Peripheral neuropathy, peripheral vascular disease (PVD), if it occurs
only in the arteries, is called PAD, gait disorders, ischemia, foot ulcers,
infections, gangrenes, Charcot neuroarthropathy, and lower extremity
amputations are some of the lower limb complications observed in pa-
tients with diabetes557,558. Lack of sanitation and hygiene, socio-cultural
practices such as barefoot walking indoors and at religious places, walk-
ing on fire, a lack of awareness on the use of proper footwear, and a dearth
of foot care clinics, together with economic factors exacerbate diabetic
foot complications in India559,560.
Diabetic foot ulcers and peripheral arterial disease

In India, DFUs [Figure 10] affect 25% of total diabetic patients during
their lifetime and are one of the most common reasons for hospitalization
and amputation. The cost of diabetic foot care in India is among the
highest in the world561 (~5.7 years of average annual income).
Neuropathy and PVD are important risk factors in diabetic foot infections562–
564
that are a significant cause of amputation and mortality amongst patients
with diabetes in India565,566. While the prevalence of neuropathy has been
estimated to be ~15%,567 PVD prevalence varies across geographies. A
lower prevalence has been reported among Indians compared to Western
countries (13% versus 48%);568 a younger patient population, a shorter
lifespan of patients with diabetes, and a lower proportion of smokers could
be plausible reasons for this difference.564,568,569The presence of PVD and
claudication in patients with diabetes indicates PAD, leading to a higher risk
of cardiovascular mortality and morbidity.[487] Recently, COVID-19 has
been associated with an increased risk of thrombotic complications, including
the peripheral ischemic foot. It needs heightened screening with ABI in
patients with a history of COVID-19.570,571 Despite the prevalence of PAD
being estimated to be 50- 60% amongst patients with DFU, appropriate and
timely diagnosis of PAD [Figure 10] is still a major concern and a leading
cause of amputation in patients with diabetes572 . Figure 9: Pathogenesis of diabetic foot ulcer. Adapted from Boulton
et al., 2018573.
Charcot neuroarthropathy
The Charcot neuroarthropathy is a major consequence of diabetic neu-
ropathy that leads to bone deformities, subluxation, and dislocation re-
sulting in inflammation characterized by a reddish, hot, swollen foot: the
Charcot’s foot. The classic “rocker-bottom” foot is an example of an end-
stage disease with severe fracture dislocation, the collapse of the midfoot,
dorsal dislocation of the metatarsals, and plantar dislocation of the tarsal
bones.573–575 The prevalence ranges from 0.4%-13% among patients with
diabetes, with a mortality rate of 28%. Using X-ray and MRI, the detec-
tion rates increase to ~30% and 75%, respectively.574
Diagnosis of Charcot’s foot is often delayed or missed and can lead to severe
foot deformity, ulceration, infection and/or lower extremity amputation.575
Initial diagnosis includes testing for sensory neuropathy done using a 128-
Hz tuning fork, a 10-g monofilament, or by testing light-touch perception.
Treatment is primarily conservative, with early treatment options being off- Figure 10: Vascular examination for PAD diagnosis. Adapted from
loading with total contact casting (TCC) and non-weight bearing in a cast or Boulton et al., 2018;573 PAD: Peripheral artery disease; TcpO2:
wheelchair until the acute inflammatory process subsides (may take weeks or Transcutaneous oximetry
months). A prefabricated orthosis device such as a Charcot Restraint Orthotic
Walker (CROW) may also be used. Overall, the fixation period depends on Considerations
reduced edema and a drop in skin temperature below 2°C compared to the Identifying a diabetic patient at-risk of a foot ulcer is an important step in
contralateral extremity. Late treatment requires reconstructive surgery to re- the timely management of future complications. The panel recommended
pair the deformity and obtain a plantar-grade foot. Off-loading using thera- IWGDF 2019581 risk stratification system for risk assessment and the
peutic footwear that off-loads the foot by at least 30% may be associated with corresponding frequency of foot screening and examination [Table 17].
a lower risk of recurrence.573
Diabetic foot infections

Compared to non-diabetics, patients with diabetes are more susceptible to
infections due to their impaired inflammatory response, inferior wound
healing owing to inadequate phagocytic clearance, increased oxidative stress,
and down-regulation of different growth factors resulting in defective angio-
genesis.576 The Infectious Diseases Society of America (IDSA) recommends
that the antibiotic regimen in patients with diabetic foot infections should be
based upon culture and susceptibility analysis577. Additional therapies may
include antibiotic impregnated beads, negative pressure wound therapy
(NPWT), and hyperbaric oxygen [Figure 11]578. In 2014, The Society for
Vascular Surgery (SVS) published the Threatened Limb Classification
System [Figure 13], based on three major risk factors associated with limb
amputation: Wound, Ischemia, and foot Infection (WIfI)579.
Strategies aimed at preventing foot diseases are cost-effective and can even
be cost-saving if increased education and efforts are focused on those pa-
tients with recognized risk factors for the development of foot problems.
The management of diabetic foot disease may seem poorly defined by
comparison with complications such as nephropathy, hyperlipidemia and
retinopathy, for which clear guidelines exist. A multidisciplinary team ap-
proach, particularly in specialized diabetic foot clinics, can reduce the bur-
den of diabetic foot complications in developing countries like India.
Patients not conforming to the foot care advice suffer and develop new Figure 11: Diagnosis and management of diabetic foot infection. Adapted
problems and/or require surgical procedures.580The present guideline fo- from Boulton et al., 2018.573 MDRO: Multi-drug Resistant Organism;
cuses on the various mechanisms of managing diabetic foot disease.
NWPT: Negative Wound Pressure Therapy • Tip-therm, a device that tests for temperature discrimination, was com-
The panel endorsed the IDF 2017 recommendations for the diagnosis and pared with two validated methods for detecting neuropathy-a monofil-
management of diabetic foot complications. However, few recommenda- ament and biothesiometry in a study comprising 910 diabetic patients.
tions were modified based on local factors such as limited resources and Tip-therm was found to be an inexpensive, highly sensitive, and specific
lack of quality assurance in laboratories, which were reviewed in an device for the detection of diabetic neuropathy when compared with
Indian context. biothesiometry and a monofilament590.
• Evidence suggests that abnormal plantar foot pressure may exist in
Table 17: IWGDF risk stratification diabetic patients before there is evidence of neuropathy (determined
by biothesiometry and monofilament tests). Podotrack, a novel, the
IWGDF risk Ulcer Frequency (adapted for the inexpensive method can be used as a screening test for abnormal plantar
Characteristics
category risk Indian population) foot pressure in this patient population591.
• Gait variations and restrictions in the subtalar and first
0 Very low No LOPS and no PADS Once every 12 months
metatarsophalangeal joint have been reported in cases of diabetic neu-
1 Low LOPS or PAD Once every 6-12 months ropathy even before the onset of foot deformity. They could be used as
an aid for early diagnosis592.
LOPS + PAD or
LOPS + foot
• ABI and tcPO2 may be used as predictors of ulcer healing and ampu-
2 Moderate deformity Once every 3-6 months tation, respectively; ABI = 0.6 was found to have 100% sensitivity and
LOPS + foot 70% specificity and tcPO2 = 22.5 was found to have 75% sensitivity
deformity and 100% specificity in predicting wound healing.593
LOPS or PAD + one or more of
the following: History of foot
Once every 1-3 months
Avoid walking barefoot
3 High
ulcer
And at every visit to the
• Sociocultural practices like barefoot walking indoors and in other reli-
A lower-extremity amputation
doctor gious places, use of improper footwear, and lack of knowledge regard-
(minor or major)
End-stage renal disease
ing foot care are significant contributors to diabetic foot complications
in India.567,594 Therefore, the panel emphasized educating patients on
Adapted from International Consensus on the Diabetic Foot 2019.581 LOPS: Loss of
problems associated with walking bare foot595 and advice on using
protective sensation, PAD: Peripheral artery disease
appropriate/therapeutic footwear, particularly for those at high-risk to
prevent the development of foot deformities and ulceration.596
• A questionnaire-based study evaluating the foot care knowledge and
practices with foot complications in 300 Indian patients suggests that
most were not previously educated about foot care and walked indoors
without footwear. The study emphasized that poor knowledge of foot
care and poor footwear practices are important risk factors for foot
problems in diabetes. It called for a joint effort from doctors and the
footwear industry to educate patients about foot care and improve their
choice and selection of footwear to reduce foot problems597.
Management of diabetic foot complications

• MRI has emerged as the most accurate method of diagnosing bone
Figure 12: Threatened limb classification system. Adapted from Mills infection, but bone biopsy for culture and histopathology remains the
et al., 2014;579 SVS: Society for vascular surgery criterion standard598
• Neuropathy increases the risk of amputation 1.7-fold; 12-fold if there is
deformity, and 36-fold if there is a history of previous ulceration.
Rationale And Evidence • A phase 3 multicentre study has provided evidence to support the safety
Detection and timely screening and efficacy of rhEGF formulated gel; the gel healed diabetic foot ulcers
• Vibration perception threshold (VPT) is considered as a gold standard for faster than treatment with placebo.599
the diagnosis of diabetic peripheral neuropathy. However, the use of simple • A peptide mimetic of the C-terminus of Cx43 (gap- junctional protein),
clinical scores such as NSS and diabetic neuropathy examination (DNE) alpha connexincarboxy-terminal (ACT1), when incorporated into the
scores were found to be valuable tools for the diagnosis of peripheral standard-of-care protocols, was found to be associated with a more
neuropathy in patients with diabetes.582,583 Moreover, a good correlation significant percentage of participants achieving 100% ulcer re-
between VPT score with a tuning fork, monofilament, and ankle reflex was epitheliazation and a reduced median time-to-complete-ulcer closure600.
found, suggesting that simple bedside tests are useful in clinical practice, • Imipenem was found to be the most potent antimicrobial against both
even in those in whom foot care practices are not followed584,585. Gram-Positive Cocci and Gram-Negative Bacilli. Among combination
• Using NSS and NDS in T2DM patients has been found to be a useful therapies, cefepime-tazobactum and cefoperazone-sulbactum were the
resource in evaluating diabetic sensorimotor polyneuropathy as an im- most effective. Antimethicillin-resistant Staphylococcus aureus
portant bed side tool.586–588 (MRSA) antimicrobials such as linezolid and vancomycin and an anti-
• Graduated RydelSeiffer tuning fork has a high specificity and a fairly extended spectrum of beta-lactamase (ESBLs) like imipenem and
good sensitivity in diagnosing diabetic foot problems.589 meropenem can be given to patients producing MRSA or ESBL601.
• Rivoraxaban is recommended along with the standard of care in patients • Systematic review done on RCTs published in PubMed, EMBASE,
with PAD (especially following revascularization) to reduce the inci- SCOPUS and Cochrane Library from January 1994 to December 2019
dence of adverse limb and cardiovascular events. Studies have also showed that pharmacotherapy non significantly increased time to remission
shown that Rivoraxaban for PAD is useful as well. 602–605 compared to TCC alone. A nonsignificant increase in BMC, a decrease in
foot temperature, and alkaline phosphatase were observed with interven-
Adjunctive treatment options tion. Limited evidence from available studies does not support the role of
• In a small study comprising six patients with DFU, hyperbaric oxygen anti-resorptive or anti-inflammatory drugs for earlier remission when added
therapy showed a positive effect in initiating ulcer healing compared to to offloading with total contact cast for active CN of the foot. 620
standard treatments like offloading, wound debridement, and glucose • Other studies include long-term foot outcomes following differential abate-
control.606 ment of inflammation and osteoclastogenesis, charcot neuroarthropathy in
diabetes mellitus, prevalence of mortality in Asian Indians with the same,
Pressure off-loading and outcome analysis, with the efficacy of interventions such as teriparatide
• Pressure modulation, commonly referred to as ‘off-loading’ is an im- for diabetic chronic Charcot neuroarthropathy.621–624
portant component in managing and treating diabetic foot ulcers. It • The role of Danosumab and Teriparatide for Charcot neuroarthropathy
involves mitigating pressure at an area of high vertical or shear has been highlighted by Petrova et al. and Busch-Westbroek et al. 625,626
stress607,608. Combining effective, easy-to-use off-loading devices such
as total contact casts and removable cast walkers ensure patient com- Stroke
pliance, healing foot ulcers, and avert limb amputations608,609. Rationale and Evidence
• Mandakini off-loading device610,611 and Samadhan off- loading sys- & Pioglitazone for primary stroke prevention in Asian patients with type 2
tem611,612 were found to be most economical, easy to apply and effec- diabetes and cardiovascular risk factors. Compared with patients who
tive methods to re-distribute the pressure in ulcerative areas. did not receive pioglitazone, those who administered pioglitazone had a
• A recent systematic review and meta-analysis report that compared with lower risk of developing ischemic stroke (adjusted hazard ratio: 0.78;
standard dressing changes, negative- pressure wound therapy had a 95% confidence interval: 0.62–0.95). The subgroup analyses defined by
higher rate of complete healing of ulcers (RR: 1.48; 95% CI: 1.24, different baseline features did not reveal significant alterations in the
1.76; p<0.001), shorter healing time (MD:-8.07; 95% CI:-13.70,-2.45; observed effect of pioglitazone. Moreover, a significant decreasing trend
p=0.005), greater reduction in ulcer area (MD: 12.18; 95% CI: 8.50, in ischemic stroke risk with an increase in pioglitazone dose (p-value for
15.86; p<0.00001), greater reduction in ulcer depth (MD: 40.82; 95% trend = 0.04) was observed.627
CI: 35.97, 45.67; p<0.00001), fewer amputations (RR: 0.31; 95% CI: & Pioglitazone is a potent insulin sensitizer, preserves beta-cell func-
0.15, 0.62; p=0.001) and no effect on the incidence of treatment-related tion, causes a durable reduction in HbA1c, corrects multiple compo-
adverse effects (RR, 1.12; 95% CI: 0.66, 1.89; p=0.68)613. nents of metabolic syndrome, and improves non-alcoholic fatty liver
• The risk of amputation increases with increasing severity and location of disease/non-alcoholic steatohepatitis. Adverse effects (weight gain,
the deformity and complexity/stage of Charcot neuroarthropathy, as per fluid retention, fractures) must be considered, but are diminished
Roger’s Charcot foot classification system.614 with lower doses and are arguably outweighed by these multiple
• Patients who use therapeutic footwear have demonstrated lower foot pres- benefits. With healthcare expenses attributable to diabetes increasing
sure, while those who use nontherapeutic footwear show an increased foot rapidly, this cost-effective drug requires reconsideration in the ther-
pressure, implying that therapeutic footwear is useful in reducing new ulcer- apeutic armamentarium for the disease.628
ation and, consequently the amputation rate in the diabetic population615. & In the Insulin Resistance Intervention After Stroke (IRIS) randomized
• Patients with diabetic peripheral neuropathy and/ or prior foot ulcers report a clinical trial, pioglitazone, an insulin-sensitizing agent, reduced the risk
higher incidence of falls than non-diabetics616–618. Specialty off-loading for recurrent stroke or myocardial infarction (MI) among patients with
devices, decreased sensorimotor function, musculoskeletal/neuromuscular insulin resistance. However, insulin resistance is not commonly mea-
deficits and pharmacological complications are implicated as the high inci- sured in clinical practice.629
dence observed. Novel technological advancements, such as virtual reality
proprioceptive training, may help in reducing the risk of such falls.617 Implementation
Availability of basic equipment, appropriate protocols, structured records, and
Medical Management of Charcot’s foot recall systems need to be supported by proper training for professionals
• In the trial by Das et al., to assess the effect of methylprednisolone (MP) providing screening and management services. Standard care of diabetic foot
or zoledronic acid (ZA) for resolution of active Charcot neuropathy complications includes maintaining adequate vascular supply, preventing and
(CN), it was observed that there was no added benefit of ZA for earlier treating soft-tissue and bone infection, performing initial excisional debride-
remission of CN as compared with TCC alone, as previously document- ment and maintenance debridement as inducted, and adhering to high-quality
ed. The strengths of this study include an intensive follow-up, a com- off-loading. Liaison needs to be established with orthoptists, footwear sup-
parison of a potent anti-inflammatory agent (MP) with ZA and TCC, pliers, and cast technicians. Multidisciplinary management programs should
and a prospective analysis of BTMs and inflammatory markers. In con- be initiated focusing on prevention, education, regular foot examinations,
clusion, MP does not reduce time to remission in active CN of the foot aggressive intervention, and optimal use of therapeutic footwear.
despite the reduction in inflammatory cytokines.619
DIABETES AND HEART (DCM). Furthermore, compared to patients without diabetes, T2DM patients
Recommendations have a considerably higher risk of CV morbidity and mortality.632 In addition,
the coexistence of risk factors like hypertension, dyslipidemia, obesity and
Recommended Care smoking with T2DM may increase the burden and complications of CVD.633
In India, CVD attributes to nearly 25% of all deaths. Apart from increasing
• Cardiovascular risk factors that should be assessed in all patients at diagnosis and
annually including
age and obesity, diabetic people have a 33% greater risk for hospitalization for
- Dyslipidemia HF. Even individuals with PD have a 9-58% greater risk to develop HF with
- Hypertension an extended risk for all cause mortality and cardiac outcomes as per a recent
- Smoking status review.634 Furthermore, according to the Global Burden of Disease study,
- Family history of premature coronary disease age-standardized CVD mortality rate was 272 per 100000 population in
- Presence of albuminuria including micro-albuminuria >30 mg.
- Body mass index (BMI) ≥25
India, which was higher than the global average of 235 per 100000 popula-
- Presence of hyperuricemia tion.635 An Indian population-based study in 6198 patients with T2DM that
- Duration of diabetes evaluated the prevalence of CVD risk factors reported that, compared to
- Screening for heart failure on the basis of 2022 AHA/ACC/HFSA Guideline for participants with diabetes versus those without it, prevalence of hypertension
the Management of Heart Failure. 630
was 73.1% (95% CI: 67.2 to 75.0) vs 26.5% (25.2 to 27.8), hypercholester-
- Presence of retinopathy as it doubles the risk of CVD 631
- Sleep duration has also been added as a new parameter for CVD risk olemia was 41.4% (38.3 to 44.5) vs 14.7% (13.7 to 15.7), hypertriglyc-
• Current or previous CVD events, age, body weight, BP and pulse, of patients should eridemia was 71.0% (68.1 to 73.8) vs 30.2% (28.8 to 31.5), low HDL-C
be recorded during their first and subsequent visits was 78.5% (75.9 to 80.1) vs 37.1% (35.7 to 38.5), and incidence of smoking/
• UKPDS risk engine and QRISK3 are simple and effective tools for smokeless tobacco use was 26.6% (23.8 to 29.4) vs 14.4% (13.4 to 15.4;
identifying and predicting CVD risks in patients with T2DM and should be
recommended for identifying high risk individuals*
p<0.001).636 *
• Patients with diabetes and CVD risk should follow the ABC treatment goals** Several landmark studies have reported that patients with T2DM are at
- A (HbA1c): <7% increased risk for several cardiovascular complications. A brief overview
- B (BP): <130/80 mmHg of the CINDI studies, INTEHEART and INTERSTROKE is presented in
- C (Cholesterol -LDL): <100 mg/dL
Table.637–640 Therefore, aggressive control of these risk factors may delay
• CV Risk assessment is to be done in all type 2 diabetes patients with multiple risk factors.
• Primary prevention is important for those at risk of Heart failure (stage A) or pre HF(stage B) or reduce the incidence of CVDs in T2DM patients.
• All patients should be managed with lifestyle intervention including physical exercise
and medical nutrition therapy Considerations
• In high-risk patients, low dose aspirin therapy should be administered along with When framing recommendations for diabetes and CV risk, following factors
lifestyle intervention
• Statins should be added to lifestyle intervention in all patients with CVD risk, if not
should be reviewed: hypertension, smoking, obesity, increased fasting insu-
contraindicated. The intensity can be modified or titrated according to patient’s lin and Insulin Resistance (IR), lifestyle intervention, atherogenic lipid pro-
CVD risk, age, side-effects, tolerability, LDL-C levels etc. file (abnormal cholesterol, high triglycerides, high LDL-C).
• Glycemic control with glucose lowering drugs that are proven to be CV safe Primary prevention of CVDs aims at preventing patients from the event of
and beneficial should be recommended to reduce CVD risk and complications
CHD/CVD. This includes engaging in moderate physical activity, maintain-
in patients with T2DM. SGLT2 inhibitors and GLP-1 receptor agonists are
approved by various regulatory authorities for CV risk reductions, apart from
ing normal body weight, limiting alcohol consumption, reduction of sodium
their glucose lowering ability. intake, maintaining adequate intake of potassium, and consumption of a diet
• Weight control should be an important consideration, while choosing glucose rich in fruits, vegetables, and low-fat dairy products with less saturated and
lowering therapy in overweight/obese persons total fat. Secondary prevention of CVDs in patients with diabetes plans to
• Pharmacological antihypertensive therapy with subsequent titration in addition reduce the mortality and morbidity and prevent the repeated CVD event. This
to lifestyle therapy should be initiated in patients with confirmed office-based
BP of >140/90 mmHg
comprises treatment with aspirin, β-blockers, ACE inhibitors and statin. The
• Pharmacological therapy for patients with diabetes and hypertension should tertiary prevention intends at rehabilitation, preventing complications, and
comprise a regimen that includes ACE inhibitor/ARB, thiazide diuretics, calcium improving QoL. This can be achieved with some interventional surgical
channel blockers, and selective β blockers. If one class is not tolerated, it should be procedures. Quaternary prevention targets at preventing over diagnosis, over
substituted with molecules from other classes; however, FDCs of different drug medicalization, over labeling and over treatment.
classes may be preferred in patients with diabetes to reduce CVD risks and
complications and increase compliance.
• ACE inhibitors are the drug of choice for diabetes, if not contraindicated; and ARBs
may be used if ACE inhibitors are not tolerated Rationale and Evidence
• Other medications for dyslipidemia (fibrates, ezetimibe, concentrated omega-3 Identification
fatty acids, PCSK9 inhibitors, Bempedoic Acid-Recommended DCGI Approved)
Cardiovascular risk factors such as dyslipidemia, hypertension, smoking,
can be considered in patients failing to reach targets with conventional lipid
lowering medications high body-mass index (BMI), family history of premature coronary dis-
ease and the presence of albuminuria and hyperuricemia should be
assessed at least annually in all patients with T2DM.633,641,642 Even the
*The treatment target goals should be individualized according to age, CINDI and CINDI 2 studies in Indian population recommend screening
risk and comorbidity. **Risk factor: Low-density lipoprotein (LDL)-cho- of CV complications at the time of diagnosis.637,638
lesterol ≥100mg/dL (2.6 mmol/L), high blood pressure (> 140/90 mm The following tools have been used by several physicians for assessment
Hg), smoking, overweight/obese, lack of physical activity of the CVD risk in individuals with diabetes and CVD.
• QRISK3 Risk Score643,644
Limited Care • UKPDS Risk Engine.645
• Cardiovascular risk factors like albuminuria and hypertension should be assessed in
Recently, the DISCOVER observational study (N=15,992) has been initiated
all patients at diagnosis and annually
• Cardiovascular risk may be calculated by using different assessment tools for people to collect real world data from 38 countries to understand patterns of T2DM
with diabetes as recommended care in patients who initiated a second-line glucose-lowering therapy. Data
from several lower-middle and upper-middle income countries collected for
the first time through DISCOVER revealed that 26.7% of the patients Across
Background Region Range (ARR) had HbA1C >9%, with highest populations in South-
Patients with T2DM are always at higher risk for several CVDs such as CAD, East Asia (35.6%) mostly attributed to low education level, low country
CHF,(both HFpEF,HFrEF), stroke, PAD, and dilated cardiomyopathy income and larger time in initiation of second line therapy.646
Table 18: Studies assessing cardiovascular risk factors Management

Lifestyle intervention
Study CINDI CINDI 2 INTERHEAR INTERSTROK
characteris (India, 2014) (India, 2016) T (Global, E (Global,
tic 2004) 2016) Early identification of metabolic syndromes such as AO, elevated BP,
hypertriglyceridemia, reduced HDL cholesterol, borderline high-risk
Study 4600 newly 1500 15,152 cases 13,447 cases
population diagnosed newly with acute (10,388 with LDL cholesterol and IFG (110 to 126 mg/dL) and design interventions
patients detected MI, 14,820 ischemic to reduce the CVD risks are the major goals of the primary prevention.647
with young- controls stroke and Furthermore, close monitoring and maintaining recommended targets for
T2DM onset from 52 3059 BP (130/80 mmHg), lipid control (LDL <100 mg/dL), and glycaemia
(men: diabetes countries intracerebral
67%) patients hemorrhage)
(A1C <7%) is important for the prevention of CVD in patients with
(men: and 13,472 T2DM.647,648 In addition, physical exercise, weight control, lifestyle
74%) controls modification with changing food habits, and cessation of smoking also
from 32 prevents the CVD risk in T2DM patients.647
countries (men:
59.6%)
• Diet: In the PURE study (N=135,335), a diet rich in carbohydrates was
shown to be associated with higher risk of total mortality. Surprisingly,
Study To assess To evaluate To assess To assess both, total fat and individual fat type were not correlated with CVD,
objective patients for patients for relationship relationship
diabetic complicatio between between stroke
CVD-related mortality or MI. In fact, saturated fat had an inverse cor-
complicatio ns of smoking, and its risk relation to stroke.649Therefore, a high carbohydrate intake is a potent
ns, diabetes and history of factors risk factor of CVD and mortality. Current nutritional recommendations
hypertensio CV risk hypertensio including for patients with T2DM propose restricting the total carbohydrate intake
n, factors such n or hypertension, to ~45-50% of the total energy. Moreover, there is increased focus on
dyslipidemi BMI, diabetes, physical
a, hypertension WHR, activity,
the quality of carbohydrate intake, with an emphasis on including com-
BMI, , dietary ApoB/ApoA1 plex carbohydrates like brown rice and whole grain wheat into the
diagnosis of dyslipidemia patterns, ratio, diet, diet.650
retinopathy, , and physical WHR, • Substitution of dietary saturated fat with PUFAs is reported to be asso-
neuropathy smoking activity, psychosocial
and consumption factors, current
ciated with improved CV outcomes. Moreover, American Family
nephropathy of alcohol, smoking, Physicians (AFP) advocates that the Mediterranean diet can reduce
blood Apo, alcohol CV mortality and the DASH eating plan is associated with a reduced
and consumption risk of CHD.651 Moreover, the following dietary adaptations can be
psychosocial and diabetes
made to lessen the development of CVDs in T2DM patients: reductions
factors to MI
in caloric intake (by 500 kcal/day to 800 kcal/day), total fat intake
Results Hypertensi Hypertension Diabetes, Previous
(especially saturated fat) and food portion sizes, increased consumption
overview on, obesity , along with history of of dietary fiber, and moderate alcohol use.652
and dyslipidemia, smoking hypertension or • Physical activity: It is an independent and protective risk factor associ-
dyslipidem BMI >23 raised ApoB/ BP of 140/90 ated with reduced CV morbidity and mortality (OR, 0.86; p<0.0001),
ia were kg/m2, and ApoA1 ratio, mm Hg or
present in smoking history of higher, regular
and physical inactivity accounts for 12.2% of the population-
23.3%, were present hypertension, physical attributable risk for acute MI and 6% of CHD with an estimated 0.68
26% in 27.6%, abdominal activity, WHR, year reduction in life expectancy.651 The exercise- based cardiac reha-
and 62.4%, 84.2 obesity, psychosocial bilitation (CR) is the cornerstone for secondary prevention of CVD. CR
27% and psychosocial factors,
patients, 24% factor, lack smoking,
is associated with a 13% and 26% lower all-cause and CVD mortality,
respecti patients. of daily cardiac causes, respectively and a 31% reduction in hospital admissions at 12 months in
vely Diabetic consumption alcohol patients with CHD.651
retinopathy, of fruits and consumption • Stress management: Evidence state that psychosocial stress has an as-
neuropathy, vegetables and
and regular DM were all
sociation with the etiology and pathogenesis of CVDs.653 Most notably,
nephropathy alcohol associated with the INTERHEART and INTERSTOKE studies report that psychologi-
were seen in consumption, stroke. cal factors have a strong effect towards MI (OR: 2.67, PAR 32.5%,
5.1%, and lack of Hypertension p<0.0001) and ischemic stroke (OR: 2·20, 1·78, 2·72; 17·4%, 13·1,
13.2%, and regular was more
22·6) respectively.639,640 In an RCT, cognitive behavioral therapy
0.9%. physical associated with
Ischemic activity were intracerebral (CBT) had a 41% lower rate of fatal and non-fatal first recurrent CVD
heart all hemorrhage than events (HR:0.59; 95% CI: 0.42,0.83; p=0.002), 45% fewer recurrent
disease, significantly with ischemic acute MI (HR: 0.55, 95% CI: 0.36, 0.85; p=0.007), and a non- signif-
PVD, and related to stroke, whereas
icant 28% lower all-cause mortality (HR: 0.72, 95% CI: 0.40, 1.30;
stroke were acute current smoking,
presented in myocardial diabetes, Apo, p=0.28) than the reference group after adjustment for other outcome-
0.7%, 2%, infarction and cardiac affecting variables during a mean 94 months of follow-up period.654
and (P<0.0001 for causes were Nonetheless, a recent Cochrane review did not find such associations
0.1%. all risk factors more associated of CVD events with the psychological interventions in CHD patients.655
95.33% and) with ischemic
needed statin stroke
therapy (P<0.0001) Pharmacological management
• Medical treatment with pharmacotherapies like aspirin, lipid lowering
drugs and BP controlling agents improves survival, extends QoL, re-
DM: Diabetes mellitus, Apo: Apolipoproteins, BMI: Body mass index, MI: Myocardial duces the need for intervention procedures, such as angioplasty and
infarction; T2DM: Type 2 DM, PVD: Peripheral vascular disease, coronary artery bypass graft surgery, and decreases the incidence of
WHR: Waist-to-hip ratio, BP: Blood pressure subsequent MI.656
Antiplatelet therapy intervention according to patient age and ASCVD risk factors.
• Aspirin is widely used for secondary prevention of CVD however; its 3,633
The details have been given in Annexure 6. The Lipid
use in primary prevention is still controversial.[534] In the recent Association of India expert consensus statement 2016 revealed that
ASCEND study, aspirin use prevented serious vascular events in pa- statin therapy is highly effective in lowering Non-HDL-C, LDL-C,
tients with diabetes with no evident cardiovascular disease at trial entry. apolipoprotein B, and remnant cholesterol, besides being remarkably
However, these preventive benefits were counterbalanced with major safe.672 Recent evidence shows a clear CVD benefit of lowering LDL-C
bleeding hazards.657 Furthermore, a meta- analysis demonstrated 35% with ezetimibe on top of a statin in patients with T2DM.673
reduction in MI among men (RR: 0.65; 95% CI: 0.51,0.82; p<0.01), but • Furthermore, in CHD/CHD risk-equivalent patients ezetimibe addition
the results were not significant in women (RR: 0.90; 95% CI: 0.71, onto simvastatin, atorvastatin, or rosuvastatin provided greater LDL-C
1.14; p=0.37).658However, a systematic review including 10 RCTs re- reductions and goal attainment than up-titrating statin therapies.674 The
ported no CVD benefit and trials with diabetes subgroup analyses also Fenofibrate Intervention and Event Lowering in Diabetes (FIELD)
did not show any effect.659 Similarly, a recent meta-analysis evaluated study assessed the effect of fenofibrate on CV events in T2DM patients.
aspirin for primary prevention of CVD in patients with diabetes and Fenofibrate reduced total CV events, mainly due to fewer non-fatal MI
reported no difference with respect to the risk of all- cause mortality and revascularizations but, did not significantly reduce the risk of cor-
(OR: 0.93, 95% CI: 0.81, 1.06), individual atherosclerotic events, bleed- onary events such as CHD death or non-fatal MI.675 But the recent
ing, gastrointestinal bleeding, or hemorrhagic stroke rates compared to ACCORDION Study done on the surviving patients (N=853) of the
placebo. 660 Furthermore, a meta-analysis (n = 4000) by the ACCORD study continued fenofibrate, claimed that the incidence rate
Antithrombotic Trialists’ (ATT) collaborators showed that the effects in the fenofibrate group were lower with respect to all-cause mortality
of aspirin on major vascular events were similar for patients with or (ACM) CVD-mortality, Non-fatal MI,CCF and major Coronary Events
without diabetes: (RR: 0.88, 95% CI: 0.67, 1.15) and (RR: 0.87, 95% than placebo in the post-trial group. Allocation to combined statin and
CI: 0.79, 0.96) respectively.661 fenofibrate showed a beneficial effect on ACM by 35% (Adjusted
• Based on cumulative data, the US Preventive Services Task Force HR=0.65; 95% CI-0.45-0.94; P=0.02).676
(USPSTF) updated its 2016 recommendations on the use of aspirin • Furthermore, USFDA states that the current evidence base is insufficient
for the primary prevention of CVD. The 2022 USPSTF recommenda- to support fibrates for CVD protection and that more trial evidence is
tions suggest that the decision to initiate low-dose aspirin for the pri- needed.677 Nonetheless, prescribing lipid-lowering agents in older peo-
mary prevention of CVD in adults aged 40 to 59 years who have a 10% ple with T2DM (>85 years) requires special consideration because ex-
or greater 10-year CVD risk should be an individual one (C statement), posure to higher doses (or higher potency) might increase the risk of
and recommends against initiating low-dose aspirin use for the primary adverse effects instead of improving life expectancy. As per LAI guide-
prevention of CVD in adults aged 60 years or older (D statement). In lines too, fibrates should be added when the TG level goes above 500
patients with aspirin intolerance/allergy or patients at very high-risk for mg/dl.
CVD, clopidogrel is recommended633,662 Evidence suggests that clo- • Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates degra-
pidogrel was significantly more effective than aspirin in secondary pre- dation of LDL-receptors (LDLR). PCSK9 inhibitors, such as
vention of CVD in patients with diabetes.662 Furthermore, dual anti- evolocumab and alirocumab, have been shown to enhance recirculation
platelet therapy may be reasonable for up to a year after ACS.633 of LDLRs to the surface of hepatocyte cells and accelerate clearance of
• A Cochrane systematic review report demonstrated that use of clopid- circulating LDL-C. PCSK9 inhibitors can prove to be a valuable treat-
ogrel plus aspirin was associated with a reduction in the risk of CV ment option for statin-intolerant patients.678
events and an increased risk of bleeding compared with aspirin alone.
However, only in patients with acute non-ST coronary syndrome, ben- Glucose lowering drugs
efits outweigh harms.663 • Intensive glycemic control with antidiabetic drugs [Table 1] reduces CV
risk and complications in patients with T2DM. A meta-analysis includ-
Lipid lowering agents ing large, long-term prospective RCTs (such as the UKPDS, the pro-
• A high prevalence of lipid abnormality in patients with T2DM positions spective pioglitazone clinical trial in macrovascular events [PROactive],
them at high risk category in the CVD risk stratifications. Elevated levels of the Action in Diabetes and Vascular Disease: Preterax and Diamicron
atherogenic cholesterol (AC), generally measured as non HDL-C, plays a MR Controlled Evaluation [ADVANCE] trial, the Veterans Affairs
central role in CVD, especially among Asian Indians.664 Diabetes Trial [VADT] and the Action to Control Cardiovascular Risk
• For management of dyslipidemia, the primary goal is to reduce LDL-C in Diabetes [ACCORD] trial) report that intensive glycemic control was
levels to <100 mg/dL by addition of drug therapy (statins) to maximal associated with 17% reduction in events of nonfatal MI (OR 0.83; 95%
diet therapy. Furthermore, fibrates may be added if triglycerides remain CI: 0.75–0.93), and a 15% reduction in events of CHD (OR, 0.85; 0.77–
>200 mg/dL in patients receiving statin therapy.656 Statins reported a 0.93); however the study did not find any significant effect on events of
significant benefit in CV risk reduction and showed significant primary stroke (0.93, 0.81–1.06) or all-cause mortality (1.02, 0.87–1.19).679
and secondary prevention of CVD/CAD deaths in patients with diabe- • DPP4, dipeptidyl peptidase 4; GIP, gastric inhibitory polypetide; GLP-
tes.665–667 1, glucagon-like peptide-1;SGLT2, sodium-glucose transport protein 2.
• A recent meta-analysis investigating 4,351 diabetes patients reported • In a meta-analysis of 301 clinical trials, the CVD risk of all glucose-
that compared with placebo, standard-dose statin treatment resulted in lowering drugs including; metformin, sulphonylurea, thiazolidinedione,
a significant RRR of 15% in the occurrence of any major CV or cere- DPP4 inhibitor, AGI, SGLT2 inhibitors, GLP-1 analogue, meglitinides,
brovascular event (RR: 0.85, 95% CI: 0.79, 0.91). Compared with and insulins, were evaluated. The results indicated that there were no
standard- dose statin treatment (simvastatin 20 mg, pravastatin 40 mg significant differences in the association between any of the nine
or atorvastatin 10 mg), intensive-dose statin (simvastatin 80 mg or glucose-lowering drugs alone or in combination and risk of CV
atorvastatin 80 mg) treatment resulted in an additional 9% RRR.668 mortality.680
• Moreover, statins were reported to produce similar results in various • SGLT2 inhibitors, empagliflozin, canagliflozin, and dapagliflozine were
studies in India.669,670 Evidence advocates atorvastatin has negligible or recently shown to provide CV benefits in patients with T2DM.
no ability to increase HDL-C, which is the key feature in patients with Empagliflozin was reported to produce substantial reductions in CVD
diabetes. Thus, other statins should probably be preferred to atorvastatin death (38%) and all-cause mortality (32%), as well as in hospitalization
in patients with diabetes/MS. 671 for HF (35%), as compared with standard-of-care in EMPA- REG
• In addition ADA recommends that, either high intensity or moderate OUTCOME trial. 232 In the recently published CANVAS trial,
intensity statin therapy should be used together with lifestyle canagliflozin significantly reduced the composite of death from CV
causes, non-fatal MI, or nonfatal stroke (HR, 0.86; 95% CI, 0.75 to 0.97; of a major macrovascular or microvascular event was also reduced by
p<0.001 for non-inferiority; p=0.02 for superiority) in T2DM patients 9%.689
with established CVD or at high risk for CV events.232 • Furthermore, some patients require a combination of two drugs in order to
• Similarly DECLARE also showed similar benefits with dapagliflozine achieve a recommended BP target. Several Indian studies evaluated the
in type 2 diabetes with low CV risk. efficacy of some FDCs: losartan 50 mg plus ramipril 2.5 mg vs each
• GLP 1 analog CVOT LEADER trial, liraglutide 1.8 mg daily was alone,690,691 metoprolol extended release (XL) plus amlodipine vs losartan
associated with lower rates (patients) of death from CV causes (4.7% plus amlodipine,692 metoprolol and amlodipine,693and reported that the
vs. 6.0%, HR, 0.78; 95% CI: 0.66 to 0.93; p=0.007) or any causes FDCs were effective, safe and well-tolerated in patients with hypertension.
(8.2% vs 9.6%, HR, 0.85; 0.74 to 0.97; p=0.02) compared to placebo
in patients with T2DM.269 Therefore, using these medications early in Metabolic memory
the course of management in high risk T2DM patients could provide Metabolic memory refers to the beneficial effects of early, intensive control
potential benefits from looming CVDs. of hyperglycemia, which can help reduce chronic complications of T2DM in
• All 3 SGLT 2 I are showing significant reduction in heart failure as a later years. The STENO-2, EMPA-REG and LEADER trials have shown the
class effect. DAPA-HF681trial concluded that patients with heart failure positive effects of metabolic memory. Recent results of STENO-2 trial after
with reduced ejection fraction, the risk of worsening heart failure or 21 years follow-up reported that an intensive, multifactorial intervention
death from cardiovascular causes was lower among those who received including ACE inhibitors/ARBs demonstrated a median of 7.9 years of gain
dapagliflozin than among those who received placebo, regardless of the of life in patients with T2DM694,695The choice of individual agent for a
presence or absence of diabetes. The EMPEROR trial showed that person with diabetes may be influenced by a number of factors including
Empagliflozin reduced the combined risk of cardiovascular death or their risk profile (CV, renal, end-organ damage), preferences, and previous
hospitalization for heart failure in patients with heart failure reduced experience of therapy, as well as costs.
ejection fraction and a preserved ejection fraction, regardless of the
presence or absence of diabetes.682 Implementations
Patients with diabetes and CVD risk should be assessed for complete lipid
Recent 2022 AHA/ACC/HFSA Guidelines recommend following profile and BP measurement during their medical visits. Antiplatelet
1. HFrEF SGLT 2 I are must as one of 4 essential medicines agents, lipid lowering therapies, and antihypertensive medications along
2. HFmrEF SGLT 2 I class of recommendation 2a with lifestyle interventions should be provided with individualization and
3. New recommendations for HFpEF are made for SGLT 2 I 2a preference of each patient. Structured annual assessment and record-
keeping should be instituted.
• Furthermore, recently released top-line results from the, CAROLINA
trial (NCT01243424) showed that linagliptin was comparable to
glimepiride vis-à-vis their impact on CV morbidity and mortality in
patients with T2DM, after a median follow-up of 6.3 years.683
• In the SAVOR-TIMI 53 trial where patients were either randomized to
saxagliptin or placebo, treatment with saxagliptin was associated with a
27% increased relative risk of hospitalization for heart failure in patients
assigned to saxagliptin.224 The risk was highest in patients with elevated
levels of natriuretic peptides, previous heart failure or chronic kidney
disease.684
• Except saxagliptin, other DPP- 4 inhibitors are cardiovascular neutral
and therefore safe for the heart.685
• Major trials assessing the impact of glucose lowering agents in improv-
ing cardiovascular endpoints are schematically presented in Figure 14.
Blood pressure lowering agents.

• A tight control of BP with pharmacological therapy like ARBs, ACE
inhibitors, or β-blockers, diuretics, and calcium channel blockers helps
in minimizing CVD risks in patients with T2DM.633Tight control of
blood glucose decreases the risk of microvascular complications, Figure 13: Major trials assessing cardiovascular outcomes in patients with
whereas tight control of BP reduces both micro-and macrovascular diabetes. 3-P: 3-point; 4-P: 4-point; 5-P: 5-point. DECLARE-TIMI 58:
complications. Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence
• ADA, IDF and other organizations recommends a target BP of 130/ of Cardiovascular Events; ESRD: End-stage renal disease; HARMONY
80 mmHg in diabetes patients.264,633 Furthermore, patients with con- Outcomes: Effect of Albiglutide, When Added to Standard Blood
firmed office-based BP >140/90 mmHg in addition to lifestyle therapy Glucose Lowering Therapies, on Major Cardiovascular Events in
should be initiated with pharmacological therapy to achieve BP Subjects With Type 2 Diabetes Mellitus; PIONEER 6: A Trial
goals.633 Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects
• A meta-analysis including 147 RCTs involving 464,164 people report a With Type 2 Diabetes; REWIND: Researching Cardiovascular Events
significant reduction in risk of coronary events (20–25%) and stroke With a Weekly Incretin in Diabetes; VERTIS CV: Cardiovascular
(30–45%) with all five BP lowering agents. However, calcium channel Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus
blockers had a greater preventive effect on stroke (RR 0.92, 95% CI: Participants With Vascular Disease. Adapted from Cefalu et al., 201856
0.85 to 0.98).[584]
• Two meta-analyses and ACCORD study reported that intensive BP Amplitude O trial- In this trial involving participants with type 2 diabe-
control was associated with a reduction of stroke event, albeit with tes who had either a history of cardiovascular disease or current kidney
greater adverse effects.686–688 In addition, in the ADVANCE trial, a disease plus at least one other cardiovascular risk factor, the risk of car-
fixed combination of perindopril and indapamide was associated with diovascular events was lower among those who received weekly subcu-
mean reduction in SBP of 5.6 mmHg and DBP of 2.2 mm of Hg after a taneous injections of efpeglenatide at a dose of 4 or 6 mg than among
mean of 4.3 years of follow-up in patients with T2DM. The relative risk those who received placebo.696
OTHER COMPLICATIONS- BONE, SKIN AND at risk of fracture. Often oral bisphosphonates are preferred in low and
HEPATOMEGALY moderate-risk cases.
TYPE 2 DIABETES MELLITUS AND OSTEOPOROSIS Recommendations for the management of osteoporosis in chronic kid-
Recommended Care ney disease (CKD) patients and those on dialysis
• Management of patients with osteoporosis and CKD is difficult as
Screening bisphosphonates are contraindicated in stage 4 and 5 kidney disease
• Screening for osteoporosis by ordering a DXA test should perhaps be (eGFR below 30 to 35 ml/min). Denosumab is not cleared by the kid-
more liberal in patient with diabetes (PWD). The IOF recommends that ney and therefore can be used in these patients. However, the risk of
both men and women over the age of 50 should be screened. Since that hypocalcemia is high with this agent, especially in patients in stage 5
seems impractical, we have suggested in our review that all over 60 disease. Optimal calcium intake and vitamin D status should be assured
should be screened, and those between 50 and 60 with at least 10 years before starting denosumab.
diabetes duration should be screened. This is a suggestion and based on • A major concern with antiresorptive therapy in patients with CKD is
resource logistics, but also on the fact that the risk of fractures only adynamic bone disease and selected patients should undergo
increases after 5-10 years of diabetes. The point about screening must undecalcified iliac bone biopsy if facilities are available, to guide correct
be emphasized so that more people with diabetes are evaluated for their decision making for the management of osteoporosis.
bone health and measures instituted early rather than acting after the
occurrence of fracture.697–699 Recommendations for HRT
• Treatment for osteoporosis in people with type 2 should be considered at • Although effective in increasing bone mass and prevent fractures, HRT
a T score of -2 rather than -2.5 is not recommended for managing osteoporosis due to high risk of side
• Bone turnover markers are often "not high" and people with diabetes effects such cardiac events and breast cancer (although breast cancer
and must be interpreted with caution. The response of these markers to risk is not increased with estrogens alone). HRT can be used when there
treatment is not altered - they will still reflect efficacy of treatment. is additional indication to use estrogens such as uncontrollable meno-
• If FRAX is used, Rheumatoid arthritis should be ticked as a risk factor in pausal symptoms. In select cases (within the first 10 years after meno-
PWD since the risk conferred is about the same. pause in women without contraindications), HRT can be used for pre-
vention of postmenopausal osteoporosis.
Initial first-line therapy for individuals with prevalent vertebral • Testosterone therapy may be added in androgen deficient men (testosterone
fractures level less than 200 ng/dL on more than one determination) if accompanied
• Teriparatide is an effective anabolic agent to initiate therapy in these by signs or symptoms of androgen deficiency (e.g. low libido, unexplained
cases- to be continued for 24 months and followed by antiresorptive. chronic fatigue, loss of body hair, hot flushes, etc.) or “organic”
• Intravenous zoledronic acid or denosumab are also effective options. hypogonadism (due to hypothalamic, pituitary, or specific testicular disor-
Since the protocol for discontinuing denosumab is still not firmly es- der). If testosterone treatment does not alleviate symptoms of androgen
tablished, zoledronic acid is usually preferred as initial therapy for 3-5 deficiency after 3–6 months, it should be discontinued, and other therapies
years. considered. It should be noted that anti-resorptive and anabolic drug thera-
• Oral bisphosphonates can be used if the patient wants to avoid injectable pies are equally effective for osteoporosis in men as well.
therapies.
Recommendations for intranasal calcitonin in the management of
Initial first line therapy for individuals with prevalent hip fracture osteoporosis
• Intravenous zoledronic acid is the agent of choice in this group- it is • Intranasal calcitonin can be used for temporary bone pain relief. However,
recommended that hospitalized/post-surgical patients with hip fractures calcitonin's effectiveness in the prevention of osteoporotic fractures is very
be given a dose of intravenous zoledronic acid before being discharged limited and should therefore be prescribed only in women who cannot
from the hospital. tolerate bisphosphonates, denosumab, teriparatide, or raloxifene or for
• Denosumab is also an apt and effective choice but is often used after whom these therapies are not considered appropriate.
zoledronic acid, for reasons explained above.
• While teriparatide can be used in this situation, there is limited data Recommendations for combination therapies
available on the prevention of hip fracture Combination therapy can be considered in patients with very high or
imminent fracture risk. The use of teriparatide and denosumab has been
Recommendations for initial first-line therapy for high-risk individuals shown to result in a great increase in BMD as against either agent alone.
without prevalent fractures However, fracture prevention data are not yet available.
• Bisphosphonates are generally agents of choice for those at high risk for
fracture. While either weekly oral (alendronate, risedronate) or annual Recommendations for sequential therapies
intravenous agents are effective, concerns about compliance and ease of • Treatment with teriparatide should always be followed by antiresorptive
once-a-year administration has made zoledronic acid the preferred drug agents to prevent bone density decline and loss of fracture efficacy.
for most patients. Both options should be discussed with the patient Either bisphosphonates or denosumab can be used in this setting.
(weekly oral vs. annual intravenous) and treatment chosen accordingly. • In patients unresponsive to anti-resorptive therapy alone, treatment can
Denosumab can be used as a first choice too if the patient reacts to or be followed by a combination of teriparatide and anti-resorptives.
wants to avoid bisphosphonates. Teriparatide can be considered for some • Treatment with denosumab, if it has to be discontinued, should be
with very low BMD (T score <-3.5) and high risk of vertebral fracture. followed by bisphosphonate, either zoledronate or alendronate in pa-
• The risk of rebound fractures is increased if subsequent doses of tients with adequate renal function. Delay in denosumab therapy or lack
denosumab are not administered in time of another therapy 6 months after last denosumab dose is associated
with a rebound increase in fractures.
Recommendations for initial first-line therapies for low and moderate-
risk cases for vertebral, non-vertebral, and hip fractures Recommendations for initial first-line therapy for high-risk individuals
• Approved agents with efficacy to reduce hip, non-vertebral, and spine without prevalent fractures
fractures include alendronate, risedronate, zoledronic acid, and • Bisphosphonates are generally agents of choice for those at high risk for
denosumab, and these are appropriate as initial therapy for most patients fracture. While either weekly oral (alendronate, risedronate) or annual
intravenous agents are effective, concerns about compliance and ease of 9. Sun exposure
once-a-year administration has made zoledronic acid the preferred drug 10. Anemia
for most patients. Both options should be discussed with the patient 11. Renal dysfunction
(weekly oral vs. annual intravenous) and treatment chosen accordingly.
Denosumab can be used as a first choice too if the patient reacts to or Diagnosis
wants to avoid bisphosphonates. Teriparatide can be considered for Clinical
some with very low BMD (T score <-3.5) and high risk of vertebral Any adult with a fragility fracture should be suspected of having under-
fracture. lying osteoporosis (primary vs. secondary). In addition, historical height
• The risk of rebound fractures is increased if subsequent doses of loss of more than 4 cm in postmenopausal women raises the possibility of
denosumab are not administered in time asymptomatic vertebral fractures. Individuals with persistent back pain
may have underlying vertebral fractures as well.
Recommendations for initial first-line therapies for low and moderate-
risk cases for vertebral, non-vertebral, and hip fractures Dual-Energy X-ray Absorptiometry (DXA)
• Approved agents with efficacy to reduce hip, non-vertebral, and spine Dual energy X-ray absorptiometry, or DXA, is the most commonly used
fractures include alendronate, risedronate, zoledronic acid, and technique for measuring BMD. Although true density measurement is 3-
denosumab, and these are appropriate as initial therapy for most patients dimensional, DXA is a two-dimensional measurement and thus calculates
at risk of fracture. Often oral bisphosphonates are preferred in low and areal bone density.
moderate risk cases. BMD values are calculated in grams per cm2 (or area of bone density). In
order to account for differences across DXA equipment across different
Recommendations for the management of osteoporosis in chronic kid- manufacturers, the values are further expressed in standard deviations
ney disease (CKD) patients and those on dialysis (SD) units from the mean BMD value of the reference population
• Management of patients with osteoporosis and CKD is difficult as • ‘T’ score of an individual is the number of SD his/her BMD deviates
bisphosphonates are contraindicated in stage 4 and 5 kidney disease from the mean BMD of 20-29-year-old reference population (usually
(eGFR below 30 to 35 ml/min). Denosumab is not cleared by the kid- Caucasian women- see further discussion below).
ney and therefore can be used in these patients. However, the risk of • ‘Z’ score of an individual is the number of SD his/her BMD deviates
hypocalcemia is high with this agent, especially in patients in stage 5 from the mean BMD of the same age, gender, and ethnic group refer-
disease. Optimal calcium intake and vitamin D status should be assured ence population.
before starting denosumab.
• A major concern with antiresorptive therapy in patients with CKD is Indications for DXA measurement
adynamic bone disease and selected patients should undergo • Women aged 60 and older and men aged 65 and older, regardless of
undecalcified iliac bone biopsy if facilities are available, to guide correct clinical risk factors
decision making for the management of osteoporosis. • Postmenopausal women younger than 60 years and men aged 50-64
years when there are concerns for osteoporosis based on their clinical
Rationale and Evidence risk factor profile
The multicentered prospective study from North India700 followed • Women in the menopausal transition if there is a specific risk factor
up 264 patients for 12 months and found that ageing, osteoporosis, associated with increased fracture risk, such as low body weight, prior
and diabetes are predictors of poor outcomes. We recommend de- low-trauma fracture, or high-risk medication
velopment of newer strategies that target male as well as female • Individuals who have had a fragility fracture before the age of 50 years
patients with osteoporosis with particular attention to preventing • Individuals with a condition (e.g., rheumatoid arthritis, diabetes
in-house falls and fractures. mellitus, malabsorption syndrome) or who are taking medication
Background (e.g., glucocorticoids in a daily dose ≥5 mg prednisone or equivalent
Osteoporosis is a skeletal disorder characterized by diminished bone for ≥ three months) associated with low bone mass or bone loss
strength that increases the risk of fracture in instances of trivial trauma. • Any individual being considered for pharmacologic therapy for osteo-
Asians have a lower bone mass than the west 701,702 porosis
Recent data suggest that type 1 and type 2 diabetes mellitus are significant
risk factor for fractures. BMD tends to be low in patients with type 1 DM, Biochemical investigations
BMD may be normal in patients with Type 2 DM and yet the fracture risk Biochemical investigations should be directed at identifying the underly-
is increased, reflecting poor bone quality in these patients.703 It is not ing cause of osteoporosis. In patients with osteoporosis, prior to initiation
known whether better control of DM mitigates the increased fracture risk. of pharmacotherapy, a basic biochemical and hormonal profile that in-
cludes serum calcium, phosphorous, total alkaline phosphatase, creati-
Implementation nine, 25-hydroxyvitamin D, and intact parathyroid hormone (iPTH)
• Screening women above 40 in the absence of any high-risk factors 704 would be desirable. In patients with secondary osteoporosis, detailed
• Screening for Vitamin D deficiency blood investigations should be pursued based on clinical suspicion.
Risk Factors Bone turnover markers(BTMs)

The following are the most common risk factors that can raise bone BTMs are dynamic parameters that reflect short-term, acute changes in
complications in diabetics 705 bone remodeling status that are not measured by BMD and are comple-
1. Gender: Women had significantly lower BMD as compared to men mentary to BMD measurement. However, BTMs have no role in the
2. Vitamin D deficiency diagnosis of osteoporosis. Although BTMs are not routinely used to di-
3. Previous fragility fracture agnose osteoporosis, they are increasingly used in the follow-up of pa-
4. Hypertension (controversial) tients who are on anti-osteoporotic treatments. Hence, wherever avail-
5. Diabetes able, patients contemplating anti-osteoporotic therapy can get a baseline
6. Cardiorespiratory illness BTM level estimated prior to initiation of therapy for subsequent com-
7. Rheumatoid arthritis (RA) parison during follow-up.
8. Smoking and alcohol
Follow up Conclusion
Treatment of osteoporosis with either anti-resorptive or osteoanabolic Osteoporosis is a major public problem in India. However, diagnosing
therapy reduces the risk of incident fractures along with a subsequent and effectively managing osteoporosis is challenging in the Indian set-
reduction in morbidity and mortality. In a study assessing treatment al- ting. Since data indicates that osteoporotic fractures occur at an earlier age
gorithms in patients with osteoporosis in India, most clinicians preferred in Indians than in the West, screening for osteoporosis should begin at an
bisphosphonates as the first-line of therapy. However, in another study earlier age. Maintaining optimum serum 25-hydroxyvitamin D levels is
that aimed explicitly to evaluate the treatment adherence and compliance essential, which, in most cases would require regular vitamin D supple-
of postmenopausal osteoporotic women for different regimens of mentation. Pharmacotherapy should be guided by the presence/absence
bisphosphonates in Indian postmenopausal women, the authors found of vertebral/hip fractures or the severity of risk based on clinical factors,
that an adherence rate of 56% was found with the monthly regimens, although bisphosphonates remain the first choice in most cases. Regular
36% for weekly regimens, and 32% for daily regimens . Herein lies the follow-up is essential to ensure adherence and response to therapy.
paramount importance of continuous monitoring and vigilant follow-up.
SKIN
Frequency of follow-up Different skin disorders in diabetes
• There exists no consensus regarding the frequency of follow-up for • Acanthosis nigricans: This condition typically affects people who are
patients on anti-osteoporotic therapy. The first follow-up can be obese and is a marker of insulin resistance. It sometimes goes away when
planned after 3 months following initiation of therapy. Thereafter, pa- a person loses weight.
tients can be followed-up at 3-6 monthly intervals for 2-3 subsequent • Diabetic dermopathy: Also known as “shin spots,” the hallmark of diabetic
contacts followed by annual visits . This promotes adequate adherence dermopathy is light brown, scaly patches of skin, often occurring on the
to the treatment regime and reinforcement of fall prevention practices. shins. These patches may be oval or circular. They’re caused by damage to
the small blood vessels that supply the tissues with nutrition and oxygen. This
Clinical follow-up skin problem is harmless and doesn’t require treatment. However, it often
• History doesn’t go away, even when blood glucose is controlled.
• Fungal infections The culprit in fungal infections of people with diabetes is
At each visit, a brief history with an emphasis on assessing new incident often Candida albicans. This yeast-like fungus can create itchy rashes of
fractures, new-onset/worsening of kyphosis/scoliosis, new-onset or wors- moist, red areas surrounded by tiny blisters and scales. These infections often
ening of back pain, and perceptible height loss should be elicited. A occur in warm, moist folds of the skin. Problem areas are under the breasts,
history of falls is a predictor of future falls and hence should be specifi- around the nails, between fingers and toes, in the corners of the mouth, under
cally queried. Patients should also be asked about the possible side effects the foreskin (in uncircumcised men), and in the armpits and groin. Common
of anti-osteoporotic therapy, notably, thigh and jaw pain. At each and fungal infections include jock itch, athlete's foot, ringworm (a ring-shaped
every visit, the need for continuation of treatment and regular follow- itchy patch), and vaginal infection that causes itching.
ups should be reinforced and family members/caregivers should be ac- • Localized itching is often caused by diabetes. It can be caused by a yeast
tively involved in decision making. infection, dry skin, or poor circulation. When poor circulation is the cause
of itching, the itchiest areas may be the lower parts of the legs.
Physical evaluation • Necrobiosis lipoidica diabeticorum: Light brown, oval, and circular patches
• A short physical examination focusing on the patient’s height should be are also a hallmark of necrobiosis lipoidica diabeticorum (NLD). This con-
undertaken. Other characteristics to assess include spinal tenderness, dition is rarer than diabetic dermopathy. In the case of NLD, though, the
kyphosis, decreased spacing between lower ribs and pelvis, and oral patches are often larger in size and fewer in number. Over time, NLD skin
hygiene. Patients on anti-resorptive therapy with poor dentition may patches may appear shiny with a red or violet border. They’re usually itchy
be referred to a dental physician for a detailed oral evaluation. and painful. As long as the sores don’t open, no treatment is required. It
affects adult women more often than men, and also tends to occur on the legs.
Drug holiday • Allergic reactions and Diabetic blisters (bullosis diabeticorum): Although
• The concept of a “drug holiday” has been proposed to potentially reduce the rare, people who have type 2 diabetes and nerve damage may also get blisters
incidence of the rare adverse events associated with long-term anti-resorp- that look like burns. They usually heal in a few weeks and aren’t painful.
tive therapy. However, the recommendation for drug holidays is still a • Eruptive xanthomatosis and Digital sclerosis: This skin condition
matter of debate, especially since there is a dearth of data from India. A causes the skin on the hands, fingers, and toes to become thick, tight,
drug holiday can be considered in low-moderate risk patients following a waxy, and potentially stiff in the joints. Elevated blood sugar can increase
course of bisphosphonate with fracture risk being revaluated every 1-3 year. the risk of developing digital sclerosis. Lotions, moisturizers, and regu-
There is no consensus on using BTMs to assess the need for drug holiday. lated blood sugar levels can help prevent or treat the condition.
• Fall prevention is an integral part of comprehensive osteoporosis care, and • Disseminated granuloma annulare: Disseminated granuloma annulare
physicians following up patients with osteoporosis should educate patients (disseminated GA) appears as red or skin-colored raised bumps that look
about fall prevention. Important points that need to be reiterated at each visit like rashes, commonly on the hands or feet. These bumps may be itchy.
include use of low-heeled shoes with rubber soles for more solid footing, They’re harmless, and medications are available for treatment.
avoiding walking on slippery floors/sidewalks, using hand rails while walk- • Acquired perforating disorders: They are caused by local trauma, rubbing
ing up or downstairs, keeping rooms, bathrooms and stairs well lit, securing or due to deposition of hydroxyapatite leading to inflammatory reaction .The
in-room carpets, and installing grab bars on the bathroom’s walls. usual presentation is keratotic papules on extensor surface that are pruritic and
• Thus, patients with osteoporosis on treatment require close monitoring may have follicular base with central plug. The retinoic acids, topical gluco-
and vigilant follow-up. A clinical assessment at 3-6 monthly intervals corticoids and PUVA therapy is useful in treating these cases.
for the initial 2-3 visits and thereafter annually would be feasible in our
setting. Wherever facilities are available, a DXA scan should be repeat- ADA Recommendation for Skin Care
ed every 2 years. If available, BTMs can be performed at least twice, at 3 • Keep good glycemic control. People with high glucose levels tend to
months and 6 months following therapy initiation, and should ideally be have dry skin and less ability to fend off harmful bacteria. Both condi-
compared with baseline pre-treatment values to assess patient compli- tions increase the risk of infection.
ance. Fracture risk should be evaluated periodically in patients on anti- • Keep skin clean and dry.
resorptive therapy, and a drug holiday can be considered in patients with • Avoid very hot baths and showers. If your skin is dry, don't use bubble
low-moderate risk of fracture. baths. Moisturizing soaps may help. Afterward, use a standard skin
lotion, but don't put lotions between toes. The extra moisture there can • Obstructive sleep apnea (important)
encourage fungus to grow.
• Prevent dry skin. Scratching dry or itchy skin can open it up and allow Screening
infection to set in. Moisturize your skin to prevent chapping, especially 1. Incorporation of the FIB-4 score into the care checklist and care path-
in cold or windy weather. way to identify patients at high risk of NASH with advanced fibrosis.
• Treat cuts right away. Wash minor cuts with soap and water. Only use • Addition of a platelet count and FIB-4 calculator to the care checklist of
an antibiotic cream or ointment if your doctor says it's okay. Cover the patient with diabetes or prediabetes.The formula for FIB-4 is readily
minor cuts with sterile gauze. See a doctor right away if you get a major available online.
cut, burn, or infection. • Involvement of a patient navigator to
• During cold, dry months, keep your home more humid. Bathe less - flag patients who need laboratory measurements for the calculation of
during this weather, if possible. FIB-4;
• Use mild shampoos. - identify patients with indeterminate or high-risk FIB-4 scores who need
• Do not use feminine hygiene sprays. referral to a specialized liver center and/or referral for VCTE;
• See a dermatologist (skin doctor) about skin problems if you are not able - follow-up to ensure that the patient underwent VCTE or the specialist
to solve them yourself. appointment.
• Take good care of your feet. Check them every day for sores and cuts. 2. Referral for VCTE
Wear broad, flat shoes that fit well. Check your shoes for foreign objects • FIB-4 <1.3: Low risk patients (patients are unlikely to have advanced
before putting them on. fibrosis). Follow-up with PCPs for appropriate preventive interventions
• Talk to your doctor or dermatologist if you are not able to solve a skin of lifestyle changes and a yearly calculation of FIB-4.
problem yourself. • FIB-4 ≥1.3: Refer the patient for VCTE
(i) if liver stiffness measure is <8 kPa: follow up with PCP and repeat
FIB-4 and VCTE in 1 year; (ii) if liver stiffness measure is ≥8 kPa: Refer
NON-ALCOHOLIC FATTY LIVER DISEASE the patient to a liver specialist.
Recommendation (Note, in case of VCTE failure, an alternative, such as shear wave
• All patients with T2DM and prediabetes be evaluated for NAFLD. They elastography/acoustic radiation force imaging, magnetic resonance elas-
recommend evaluation for NAFLD by measuring baseline and yearly tography [particularly when body mass index is >35 kg/m2] may be
liver enzymes and referral to a specialized center for persistently elevat- considered according to local availability).
ed or worsening transaminases. 3. Referral to specialized liver centers for further assessment of all patients
• The AASLD guidelines state that “there should be a high index of suspicion with FIB-4 ≥1.3 and VCTE ≥8 kPa.
for NAFLD and NASH in patients with T2DM.They recommend the use of
noninvasive measures of fibrosis, such as the NAFLD fibrosis score,
fibrosis-4 index (FIB-4), or vibration-controlled transient elastography
(VCTE) to identify those at low or high risk for advanced fibrosis.
• However, there is no clear consensus about how to implement screening
and which patients should be referred to specialized centers.
• Patients with a FIB-4 score ≥1.3 should undergo further evaluation by a
liver specialist.
Background
Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease
(NAFLD) commonly exist together and more precisely in Asian Indians.
They both are consequences or a complication of metabolic syndrome. The
presentations of NAFLD ranges from simple steatosis (NAFL) to non alco-
holic steatohepatitis (NASH), and cirrhosis. NAFLD is defined or could be
diagnosed as hepatic steatosis diagnosed either by histology/imaging with
macrovesicular steatosis in >5% of hepatocytes according to histological
analysis or by proton density fat fraction or >5.6% as assessed by proton
magnetic resonance spectroscopy (MRS) or quantitative fat/water selective
Figure 14: Screening algorithm for different populations
magnetic resonance imaging (MRI) with no secondary cause for steatosis.
Complications
overall prevalence of NAFLD in T2DM Indian population was found to be
Among macrovascular complications mainly CVD in NAFLD is in-
56.5%, which is in line with prevalence of 54.5% described by Mohan
creased by 1.87-fold in the presence of T2DM. NAFLD has been asso-
et al,10 but higher than the prevalence rate of 12.5% and 20.9% described
ciated with increased carotid intima-media thickness, increased coronary
in other studies. The corelation In Asian Indians could be predominantly due
artery calcium score, early left ventricular diastolic dysfunction, de-
to presence of excess abdominal fat (abdominal subcutaneous and intra-
creased myocardial perfusion, and reduced myocardial high-energy phos-
abdominal fat) and lifestyle factors (imbalanced diets and physical inactivity),
phate metabolism in patients with T2DM.
and presence of high grade insulin resistance.
NAFLD is also known to increase microvascular complications of diabe-
• Data on drug management needs to be updated. SGLT2i data from India
tes such as chronic kidney disease and retinopathy.
is important, as is GLP1RA data.
A strong association between NAFLD and chronic kidney disease has been
• Greater use of fibroscan has to be emphasized- ultrasound serves little
largely described in the literature.706 NASH is associated with a 2-fold
purpose.
increase risk of chronic kidney disease, and patients with advanced liver
fibrosis are at a 5-fold higher risk of chronic kidney disease compared to
Risk Factors
patients without fibrosis, independently of the presence of diabetes
• Type 2 diabetes mellitus
Diagnosis
• Metabolic syndrome
For high specific and sensitive diagnosis of NAFLD liver biopsy is the
• Obesity
investigation of choice.
• Physical inactivity
A non-invasive imaging test for steatosis is ultrasound (USG) (preferred Metformin

for first-line diagnosis which shows increased echogenicity) Metformin is considered as the first-line therapeutic agent for the treat-
MRI and proton MRS or quantitative fat/water-selective MRI/fibroscan/ ment of T2DM. Metformin decreases body fat with an improvement in
CT could be assessed as more sensitive diagnostic technique. hepatic insulin sensitivity. But for the treatment of NAFLD without dia-
betes, there is no license or proper recommendation for the use of met-
Rationale and Evidence formin. But it has been seen that there is an improved survival in cirrhosis
There have been studies done around the prevalence of clinically relevant and HCC even though definitive improvement in steatosis or histological
liver fibrosis due to non-alcoholic fatty liver disease in Indian individuals with features of NASH has not been established.
type 2 diabetes707, low skeletal muscle mass is associated with liver fibrosis in
individuals with type 2 diabetes and non-alcoholic fatty liver disease. 708 Thiazolidinediones
Pioglitazone cause adipose tissue sensitization to insulin through activa-
Randomised Controlled Trials from India: tion of PPARϒ resulting in fatty acid uptake and storage. There is also an
Effect of dulaglutide on liver fat in patients with type 2 diabetes and increase in adiponectin with amelioration of pro-inflammatory
NAFLD: randomised controlled trial (D-LIFT trial)709: This trial concluded adipokines, thus reducing gluconeogenesis and fatty acid influx improv-
that when included in the standard treatment for type 2 diabetes, dulaglutide ing insulin sensitivity. They also cause restoration of normal adipose
significantly reduces LFC and improves GGT levels in participants with tissue biology and result in an improvement in hepatic steatosis.
NAFLD. There were non-significant reductions in PFC, liver stiffness, PIVENS trial compared low-dose pioglitazone versus Vitamin E versus
serum AST and serum ALT levels. Dulaglutide could be considered for placebo for 2 years in patients without overt diabetes and concluded that
the early treatment of NAFLD in patients with type 2 diabetes. pioglitazone (improved all histological features [except for fibrosis]) and
resolution of NASH was achieved more than placebo. Cusi et al. in a
Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes double-blind randomized placebo-controlled study concluded that there
and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial was reduction in hepatic steatosis, inflammation, and ballooning without
(E-LIFT Trial)710: This trial concluded that when included in the standard worsening of fibrosis with pioglitazone in NASH with prediabetes or
treatment for type 2 diabetes, empagliflozin reduces liver fat and im- T2DM. Improvement in fibrosis, insulin sensitivity in liver, skeletal mus-
proves ALT levels in patients with type 2 diabetes and NAFLD. cle, and adipose tissue was also present and the positive outcomes were
maintained even after 36 months of treatment.
Dapagliflozin Improves Body Fat Patterning, and Hepatic and
Pancreatic Fat in Patients With Type 2 Diabetes in North India711: Glucagon-Like Peptide-1 Analogs
Trial concluded that Dapagliflozin, after 120 days of use, reduced pan- But definitive data needs to be explored.Glucagon-like peptide-1 (GLP-1)
creatic and liver fat and increased insulin sensitivity in Asian Indian analogs by its weight loss of GLP-1 receptor as seen in animal studies.
patients with T2DM. property can result in an improved hepatic steatosis and steatohepatitis
and also by the expression
Management
The interventions for the management of NAFLD should have an Insulin secretagogues: sulfonylureas
indirect effect which improves IR and glycemia as Insulin Resistance They stimulate insulin secretion and are associated with a higher risk of
(IR) is considered a major pathophysiological mechanism behind severe hypoglycemia than metformin and other drugs in patients with
NAFLD in Diabetes and thus are used for the treatment ofT2DM as advanced age and chronic liver or kidney disease. They do not modify
well as for the treatment of NAFLD also pharmacotherapy has to be IR neither any improvement is seen with perspective to NAFLD, their use
reserved for those with highest risk for disease progression in NAFLD. is not recommended specifically for NAFLD.
Definitive clinical trials are limited. NOTE - Some of the drugs such Glibenclamide (glyburide) and gliclazide are metabolized in the liver and
as ursodeoxycholic acids are not recommended for the treatment of eliminated through bile and kidney. Hepatotoxicity has been reported
NASH/NAFLD with glibenclamide and gliclazide. Therefore their use is not recommend-
ed in NAFLD or hepatic impairment.
Statins
Many patients with T2DM are treated with statins to decrease risk of Meglitinides
CVD, and in 2006 the Liver Expert Panel stated that statins can be safely Repaglinide and Nateglinide are the 2 most commonly used drugs. They
used for dyslipidemia in patients with NAFLD/NASH Statins can be used stimulate the beta cells of the pancreas, both agents are metabolized in the
in dyslipidaemia with increased baseline liver enzymes. But however liver, however, repaglinide is rapidly eliminated through the bile and its
until more randomized clinical trials prove their efficacy, statins should rate of elimination is significantly reduced in patients with CLD thus, it
not be used to specifically treat NAFLD/NASH. may induce hypoglycemia and it is contraindicated in patients with ad-
The GREACE trial also showed the safety of statins in NAFLD/NASH. vanced liver insufficiency but its use in NAFLD grade I and II could be
Although use of statins in NASH cirrhosis is safe but it should be avoided indicated. In contrast, the pharmacodynamics of Nateglinide is not altered
in decompensated cirrhosis. in patients with CLD and is considered to be safer.
Omega-3 Polyunsaturated Fatty Acid SGLT 2 I

Hypertriglyceridemia or high TG, which often coexists in NAFLD and SGLT2 inhibitors reduce plasma glucose levels by inducing glucosuria and
T2DM, can be treated with high-dose omega-3 polyunsaturated fatty acid osmotic diuresis. They should be carefully administered to patients with
(PUFAs) but their use to specifically target fatty liver is still uncertain. risks of hypovolemia (older age, cardiovascular diseases, treatment with
More detailed real world evidences are required. diuretics, liver cirrhosis with circulatory dysfunction). They are contraindi-
cated in patients with renal impairment grade IV or eGFR less than 30 mg/
Vitamin E dl. Their use in NAFLD has not been established out clear as in direct or
Oxidative stress occurs in both NAFLD and T2DM which is a predictive indirect effect. But should be avoided with higher risk of hypovolemia.
precursor for macro as well as microvascular complications. According to
PIVENS trial, 800 IU/day of Vitamin E for 96 weeks improved liver Glitazars
enzymes, steatosis, inflammation, and ballooning (except fibrosis) and Saroglitazar is a glitazar class compound that has been approved by the
induced resolution of NASH in 42% of patients. central drug standard control organization of India for treating diabetes
dyslipidemia with the excellent safety profile. Real-world evidence has Background
showed that there was also a consistent improvement in liver parameters Obesity is a highly prevalent metabolic disorder that is often associated
with reduction in ALT levels in NAFLD. Studies in northern India have with T2DM.712,713 For adults, WHO define overweight as BMI of ≥25
shown improvement in liver parameters such as SGPT in diabetic dyslip- kg/m2 and obesity as BMI of ≥30 kg/m2.714 However, WHO and
idemia patients with NAFLD who received saroglitazar. International Obesity Task Force (IOTF) suggested BMI cut-offs of 23
and 25 kg/m2 for Asian Indian adults for overweight and obesity, respec-
Bariatric Surgery tively.715,716 Furthermore, the World Health Organization Asia Pacific
Indication for bariatric surgery is noncirrhotic NASH unresponsive to Guidelines defined generalized obesity (GO, BMI ≥25 kg/m2), abdominal
lifestyle changes and pharmacotherapy. Clearance of NASH was seen obesity (AO, WC ≥90 cm for men and ≥80cm for women), and combined
in 85% of patients, and inflammation and fibrosis in 37% and 20%, obesity (CO = GO plus AO) for Asian population.715–717 In India, the
respectively. This was actually attributed to weight loss. The prevalence prevalence of obesity is rising at an alarming rate, primarily affecting the
of metabolic syndrome reduced from 70% to 14%, i.e., there was a res- urban population.712,718 The ICMR-INDIAB study data reports that about
olution of hypertension, dysglycemia, and dyslipidemia in 85%, 93.8%, 135, 153, and 107 million individuals in India might suffer from GO, AO,
and 95.6% of patients, respectively. Portal hypertension should be ex- and CO, respectively, if extrapolated to the whole country.717–719
cluded before attempting surgery. Furthermore, female gender, hypertension, diabetes, higher socioeco-
nomic status, physical inactivity, and urban residence were significantly
OBESITY AND TYPE 2 DIABETES MELLITUS associated with obesity in the Indian population. Indians have an in-
creased predisposition to diabetes attributed to the “Asian Indian
Recommended Care Phenotype” characterized by lesser GO measured by BMI and more
significant central body obesity. More truncal fat, as shown by greater
• The cut-off points for overweight and obesity in Indian patients with T2DM patients WC and WHR.712,720–724 Abdominal obesity contributes significantly to
are as follows: metabolic alterations such as Insulin Resistance (IR), dysglycemia, and
- BMI 18-22.9 kg/m2: Normal
- BMI 23-24.9 kg/m2: overweight
dyslipidemia.718,724–728 T2DM is closely linked to obesity, particularly
- BMI ≥25kg/m2: Generalized obesity adult weight gain, and is the main contributor to rising healthcare costs.
Waist circumference (WC) ≥90 cm for men and ≥80 cm for women: abdominal While it seldom develops with BMI <21 kg/m2, most people with T2DM
obesity have a BMI >25 kg/m2, and around 50% have a BMI >30 kg/m2.729
High consumption of sugars among children and adults in India may also
• Criteria for metabolic syndrome are as follows:
- Abdominal or central obesity (WC ≥90 cm for men and ≥80 cm for women) plus have clinical significance, given the increased tendency for Indians to
- Any 2 of the following four factors: develop IR, abdominal adiposity, hepatic steatosis, and the increasing
» Increased triglycerides (≥150 mg/dL or specific treatment) “epidemic” of T2DM.712,730 Because Asian Indians tend to develop dia-
» Reduced HDL cholesterol (men: <40 mg/dL; Women: <50 mg/dL or specific
betes at a significantly lower BMI and WC than white Europeans, lower
treatment)
» Increased blood pressure (systolic BP ≥130 or diastolic BP ≥85 mm Hg or
thresholds of BMI to define overweight (BMI: 23-24.9 kg/m2) and obe-
treatment of previously diagnosed hypertension) sity (BMI ≥25 kg/m2) were proposed by IDF and National Institute of
» Increased fasting plasma glucose (FPG ≥100 mg/dL or previously diagnosed Health and Care Excellence (NICE).731,732
T2DM) Considering the increasing prevalence of obesity in both developed and
Management Strategies: developing countries and a higher risk for developing IR, dyslipidemia,
• Maintaining a healthy lifestyle is recommended for the management of the metabolic dysglycemia, and a higher Cardiovascular risk at lower levels of BMI in
syndrome
Indians, a consensus meeting was convened in New Delhi in 2008733 to
• Moderate calorie restriction (to achieve a 5%-10% loss in body weight)
• At least 150 mins/week of physical activity is recommended, which includes aerobic redefine the cut-offs for BMI and WC.
exercise, work-related activity, and muscle strengthening activity. It is to be increased
to 300 mins/week. Diagnosis of Obesity and Abdominal Obesity:
• Change in dietary composition (low-calorie diet) For diagnosing overweight and obesity in the Indian population, accord-
• Combination of aerobic and resistance training exercise
• Change in behavioral pattern
ing to this consensus statement, a BMI of 18–22.9 kg/m2 should be
• Pharmacotherapy for obese patients with T2DM should be considered in addition to considered normal, a BMI of 23–24.9 kg/m2 should be regarded as over-
lifestyle changes in those with BMI >25 kg/m2 weight, and a BMI ≥25 kg/m2 indicates the presence of obesity. The
- GLP-1 analogs and SGLT2 inhibitors should be preferred as add-ons to metformin upper limit for WC for men and women was defined as 90 cm and 80
in obese patients with T2DM cm, respectively.718
- Lipase inhibitors (orlistat) may be used for inducing weight loss in addition to
OADs in patients who have BMI >25 kg/m2
• Surgical treatment (bariatric surgery) may be considered an option in patients with Normal Weight Obesity and Diabetes in India
T2DM with BMI >32.5 kg/m2 who cannot achieve sustainable weight loss and Those who are not obese by the current criteria may have higher body fat
improvement in the severity of co-morbidities, including hyperglycemia, despite and excess fat in the ectopic sites.734,735In a recent study from Kerala; it
proper nonsurgical management.
• Surgical options for weight loss surgery include:
was found that about a third of the study population (n=1147) had higher
- Restrictive procedures: Laparoscopic adjustable gastric banding (LAGB) and body fat percentage despite having a BMI in the non-obese category. The
sleeve gastrectomy. Gastric balloons/other devices may be tried if surgery cannot prevalence of diabetes, hypertension, and dyslipidemia is similar in these
be done. individuals with normal weight obesity compared to those with overt
- Malabsorptive procedures: Biliopancreatic diversions (BPD)
obesity in the Indian population.736 Moreover, this phenotype is more
- Combined procedures: Roux-en-Y gastric bypass (RYGB)
- Experimental procedures: Ileal interposition and duodenojejunal bypass, various resistant to lifestyle intervention in the Indian setting. However, more
implantable pulse generator data are needed.737
• Comprehensive lifestyle changes including dietary modification, exercise,
behavioral management and pharmacotherapy, and bariatric surgery in select COVID-19 and Obesity
patients are the most effective interventions for weight management in T2DM
patients
The COVID-19 pandemic has severely influenced the world’s lifestyle,
with no exception for the diabetic population. Weight gain due to a dis-
turbed lifestyle has been seen during the COVID-19 epidemic. The pres-
ence of obesity itself is a substantial risk factor for severe COVID-19 and
mortality738 and this could be further aggravated due to diabetes.739
Sarcopenic Obesity • Behavioral therapy should address modifiable factors such as eating
Sarcopenia is a decreased muscle strength, function, and mass predomi- patterns and exercise habits that can significantly impact the manage-
nantly due to age. Sarcopenic obesity is applied when sarcopenia is comment of obesity. A review of the Indian scenario suggested that slow
bined with excess body fat. Multiple factors are responsible for sarcope- eating techniques and stimulus control (not being distracted by televi-
nic obesity, such as lack of physical activity, malnutrition, low-grade sion, books, or other materials) positively affect weight loss.751 In obese
inflammation, and insulin resistance. It is related to excess morbidities, patients with T2DM patients, IDF recommends not only moderate cal-
mortality, and delayed recovery from any acute condition. Hence, sarco- orie restriction but also a moderate increase in physical activity as a part
penic obesity demands identification and intervention at an early stage. of behavioral therapy to promote weight loss (5–10% loss of body
Criteria from a recent Indian study (Sarco-Cubes study) could be follow- weight in the first year).752 Other essential components of behavioral
ed for the diagnosis of sarcopenia, and BMI>25 kg/m2 should be taken for therapy embrace self-monitoring, goal setting, and stimulus or cue con-
diagnosis of obesity.740 trol. Such strategies help set realistic goals, guide patients in identifying
stimuli that lead to excessive nutrient intake, and eliminate them
Obesity, Type 2 Diabetes, and Increased Risk of Cancer accordingly.753
Individuals with obesity and T2DM are at a greater risk of developing • Body weight is inversely associated with physical activity.754 Patients
multiple cancers, including breast, prostate, colorectal, gastric, pancreatic, with low physical activity have a 3-fold greater risk of significant
and hepatic.741 Multiple potential metabolic abnormalities in obesity and weight gain in men and almost a 4-fold in women.755,756 This associa-
T2DM may explain the increased risk of cancer and cancer-related mor- tion was stronger for women than men and the obese compared to
tality in these patients.742–744 average weight or overweight individuals.757 Furthermore, prolonged
exercise is associated with improved metabolism and muscle mass con-
Clinical Considerations servation during dietary restriction.758,759 An RCT comprising 262 sed-
The following factors were considered when framing recommendations entary men and women reported that a combination of aerobic and
for obesity that were reviewed in the Indian context: high prevalence of resistance training exercise reduced WC from −1.9 to −2.8 cm and mean
obesity, high abdominal adiposity, increased fasting insulin and IR, nu- fat mass of −1.7 (−2.3 to −1.1 kg; p<0.05) compared with the non-
tritional factors, atherogenic lipid profile (increased triglycerides and exercise group.760 Physical activity, including aerobic, work-related,
LDL and low HDL).733 and muscle strengthening, should be prescribed at the individual, com-
Identification of obesity in patients with type 2 diabetes munity, and societal levels to help Asian Indians become more physi-
• At first and on each subsequent visit, patients with T2DM should be cally active (Table 1). As per the WHO recommended levels of physical
screened for the presence of excess body weight using appropriate an- activity for adults (18-64 years), it should be at least 150 minutes of
thropometric measurements (BMI and WC). They should be classified moderate-intensity weekly or 75 minutes of vigorous-intensity aerobic
as overweight or obese based on cut-off values recommended for the physical exercise weekly.761
Indian population. • In the Diabetes REmission Clinical Trial (DiRECT), 306 patients with
• Based on the current evidence, WC is preferred over WHR as a measure T2DM, with a BMI of 27-45 kg/m2 and not receiving insulin, were
of abdominal obesity with Asian Indian specific cut-offs.733 Asian assessed for the remission of T2DM during a primary care-led intensive
Indians have higher morbidity at lower cut-offs for WC than the western weight management program. At 12 months, almost half of the partic-
population; ≥90 cm in men and ≥80 cm in women.726,733 Measurement ipants, 68/149 (46%), achieved remission versus 4% in the control
of waist circumference should be done by standard method.745 group to a non-diabetic state and were off antidiabetic drugs. At 24
months, 64% of those who had lost more than 10 kg were still in
Lifestyle interventions remission.762,763
• Lifestyle interventions, including diet therapy, physical activity, and • The randomized controlled PREVIEW lifestyle intervention study re-
behavioral and psychosocial strategies, have shown positive health out- ported that total physical activity accounts for more significant variance
comes in obese patients with T2DM patients. The Diabetes Prevention in IR and some related cardiometabolic risk factors than moderate-to-
Program (DPP)746 and the Look AHEAD (Action for Health in vigorous physical activity. In adults with prediabetes, objectively mea-
Diabetes) trial747 report clinically significant weight losses averaging sured physical activity and sedentary time have been associated with
4-5% (or 4–5 kg) at 3–4 years with lifestyle intervention. Similarly, an cardiometabolic risk markers.764,765 Fixed low-energy diet has been
RCT including Asian Indians reported that subjects with less education shown to induce an overall 11% weight loss and showed significant
lost a model-predicted 3.30 kg more in weight and 4.95 cm more in WC improvements in insulin resistance; men appeared to benefit more than
than those with more formal education.748 women.766
• The lifestyle interventions for overweight or obese T2DM patients should be • Short-term weight loss has also been seen with the Ketogenic diet and
based on decreased energy intake and increased energy expenditure to pro- Intermittent fasting in obese patients. However, long-term data are not
duce a negative energy balance. This includes a low-calorie diet with a available. Specifically, more trials are needed in patients with T2DM.
higher fiber intake, lower intake of saturated fats, optimal ratio of essential Therefore, prescribing aerobic and resistance training exercises in indi-
fatty acids, reduction in trans fatty acids, slightly higher protein intake, lower viduals with T2DM can improve metabolic control while reducing obe-
intake of salt, and restricted sugar intake.749 High-protein meal replacement sity and its related complications.
diet-based intervention in overweight/obese Asian Indians has shown a sig- • Caloric restriction and increased protein intake to promote muscle
nificant reduction in weight, abdominal obesity, blood pressure, lipids, gly- growth based on individual characteristics. Treatment mainly re-
cemic parameters, and hepatic enzymes compared with a standard control volves around dietary and physical activity interventions to reduce
diet in Indians.750 Although studies assessing the ideal carbohydrate intake 5-10% of body weight. There is no recommended pharmacotherapy
for people with diabetes are inconclusive, modifying carbohydrate intake for sarcopenic obesity, but the same treatments for obese patients
considering the blood glucose response is of value, especially in the Indian may be indicated.
context, where carbohydrate intake across all regions of India is very high.
Table 19: Physical activity prescription for aerobic and muscle disease and diabetic kidney disease, the usage is not as expected, mainly
strengthening exercise733 owing to the high cost of therapy and gastrointestinal adverse effects.
Besides, it is contraindicated in patients with a history of pancreatitis,
Type of Moderate Durati Frequ Vigorous Duration Frequency
physical intensity on ency/ intensity / days per
diabetic retinopathy, and medullary thyroid cancer.
activity modality days modality week In general, higher doses of GLP-1 RA would be required for weight loss
per repetitio
week ns than those used for glycemic control. An up-titration of the amount is
needed for optimal effects (Figure 1).
Aerobic Brisk 30 min 7 Football, 20 min 3
physical walking, badminto
stair n, SGLT2 Inhibitors
activity climbing, basketbal SGLT2 inhibitors promote weight loss and provide cardiovascular and
jogging (4-7 l,
running, renal benefits. They cause a more significant loss of visceral fat mass than
rope lean mass. In a double-blind RCT on patients with T2DM, SGLT2i, when
m/s), jumping, added to patients uncontrolled with metformin, reduced body weight by
cycling, dancing
treadmill 4.54 kg, waist circumference by 5.0 cm, and fat mass by 2.8 kg over 102
and weeks772. In a retrospective analysis from India, T2DM patients who lost
swimming
maximum weight were significantly younger; and had higher use of met-
Muscle Resistance
weight
1-3
sets of
2
-
Resistanc
e weight
>3 groups
of >12
2-3 formin, SGLT2i, and GLP1-RA773. Bays et al. showed that canagliflozin
training, 8-12 3 training, 100 mg reduces body weight by 2.8 kg in obese patients without diabe-
strengthen curls, repeti curls, repetition tes774. A systematic review and meta-analysis of 6 RCTs involving 872
ing presses, anti- tions presses, s individuals on the use of SGLT2i in overweight or obese adults without
activity gravity target anti- targeting
exercise, ing gravity major diabetes found that, compared to the placebo group, the SGLT2i group
isometric major exercise, had statistically significant reductions in body weight (1.42 kg vs. 1.14
isometric
kg; P<0.00001) and BMI (0.47 vs. 0.31; P<0.00001)775. 70. In a recent
exercise, muscle exercise, muscle
children- groups children- groups Indian study, a statistically significant reduction in weight, BMI, body fat,
body body circumferences, and all skinfold thickness was seen after 90 days of
treatment with dapagliflozin. Still, handgrip strength increased, meaning
weight weight
activity activity betterment of skeletal muscle function.776
(pull-ups) (pull-
ups)
GLP-1RA and SGLT2i Co-administration
Co-administering SGLT2i with GLP1-RA in obese patients without dia-
Pharmacotherapy betes reduces body weight by 4.5 kg at 24 weeks, and the weight loss was
Though lifestyle modifications effectively induce weight loss and im- maintained for up to 1 year (5.7 kg)75. A combination of SGLT2i and
prove the diabetic status, they often fail. Initiation of pharmacotherapy GLP1-RA for weight loss is expected to provide a complimentary benefit,
is required quite often. as SGLT2i causes weight loss by calorie loss and GLP1-RA promotes
Metformin is the drug of the first choice for T2DM, with some evidence weight loss by decreasing calorie intake.
of weight loss.767,768 Addition of acarbose may also produce a small
amount of weight loss. Though these two drugs have a favorable effect Figure 15: Recommendations for initial up-titration of GLP-1 RA777
on weight loss, they are not considered potent weight loss drugs. 59, 60,
61,62, 63, 64
Available choices of weight loss options in patients with T2DM are as

follows:-
Orlistat (tetrahydrolipstatin),
It is a lipase inhibitor and causes modest weight loss by blocking fat
absorption from the gut. Combined with lifestyle changes, it was found
to be effective in reducing weight and preventing diabetes.721 A recent
systematic review and meta-analysis report that treatment with orlistat
and lifestyle intervention resulted in significantly more significant weight
loss and improved glycemic control in overweight and obese T2DM
patients compared with lifestyle intervention alone.769
Anti-hyperglycemic Drugs with Potential for Weight Loss

GLP-1 Receptor Agonists
GLP-1 Receptor Agonists (GLP1 RA) were approved for the first time in
2005 to treat diabetes. Since then, newer molecules from the class have
been introduced, almost all injectable; Exenatide administered twice dai-
ly, Lixisenatide and Liraglutide once daily, Dulaglutide, Albiglutide, and Liraglutide in Children
Semaglutide once weekly. An oral GLP-1 RA, namely oral Semaglutide, The USFDA approved Liraglutide in 2019 for managing pediatric (at or
is now available in India. In part, the weight loss effect of GLP-1 RAs is above ten years of age) patients with T2DM following the landmark Ellipse
mediated by their appetite suppression effects. Additionally, they cause trial778. In 2020, it was approved for chronic weight management among
abdominal fullness and early satiety, thus reducing caloric intake770. patients with obesity aged 12 years and older, as defined by age and gender-
Further, food choices toward less calorie-dense foods may be influenced specific BMI cut-offs corresponding to an adult BMI of 30 kg/m2 or higher.
by GLPI-RA 771.
Although most guidelines worldwide recommend using GLP1 RA in Dual GIP/GLP-1 Receptor Agonist, Tirzepatide
type 2 diabetes patients with a heightened risk of atherosclerotic vascular It is the first dual GIP/GLP-1 agonist. It is a promising agent for the
treatment of both diabetes and obesity. The most common side effects
of Tirzepatide are related to the gastrointestinal tract, like nausea, Table 20: Treatment for Overweight and Obesity in Patients with
vomiting, and diarrhea 779. The USFDA approves it for the treatment of Type2 DM
diabetes. It is administered subcutaneously once a week. A systematic
review and meta-analysis showed that all doses of Tirzepatide were su- BMI≥23- BMI ≥ 25- BMI ≥32.5- BMI≥37.5
Treatment 24.9 kg/m2 32.5 kg/m2 37.4 kg/m2 kg/m2
perior to placebo, long-acting GLP-1 RAs, and basal insulin in reducing Options
HbA1c and body weight 780. Overall, it is one of the most potent drugs for * * * *
weight loss. This drug is not yet available in India. Diet and
Lifestyle
* * * *
Metabolic Surgery Medications
• The surgical options for weight loss include laparoscopic adjustable †† €€
gastric banding (LAGB), sleeve gastrectomy, Roux-en-Y gastric Surgery
bypass(RYGB), biliopancreatic diversion (BPD), ileal interposition
and duodenojejunal bypass, and various implantable pulse *Indicate treatment initiation at indicated BMI cut-off
generators.733 †† For select patients who fail to lose weight and have uncontrolled
• Metabolic surgery is indicated in patients with BMI >32.5 kg/m2 with diabetes after at least one year of medical, behavioral, and lifestyle
co-morbidity or BMI >37.5 kg/m2 without co-morbidity who fail to lose interventions
weight with medical management.733 Several studies suggest that bar- €€ For choose patients with morbid obesity can proceed directly to sur-
iatric surgery provides durable glycemic control compared with inten- gery after a detailed discussion with the patient and physician.
sive medical therapy.781–784 Moreover, gastric bypass has been ob-
served to uniquely restore the pancreatic β-cell function and reduce VACCINATIONS IN PEOPLE WITH DIABETES
visceral fat, thus reversing the core defects in diabetes.781 A systematic Recommendations
review and meta-analysis of RCTs report that RYGB surgery is superior
to medical treatment for the remission of T2DM and improvement of Recommended Care
the underlying metabolic defects and other CV risk factors.785
• Laparoscopic sleeve surgery and RYBG were safe and effective treat- • All diabetes subjects should be educated about administering at least pneumococcal and
influenza vaccines.
ment options among the obese Indian population with T2DM, with • Vaccination against pneumococcal disease, including pneumococcal pneumonia,
significant remission rates of 77% and 85%, respectively (p<0.001), with the 13-valent pneumococcal conjugate vaccine (PCV13) is recommended for
with substantial reductions in HbA1c and diabetes medication us- children before the age of 2 years.
• People with diabetes aged 2 through 64 should receive a 23-valent pneumococcal
age.786–788 polysaccharide vaccine (PPSV23). At age ≥65 years, regardless of vaccination history,
additional PPSV23 vaccination is necessary.
Medical Devices for Weight loss and Weight Management • Annual vaccination against influenza is recommended for all people ≥6 months of age,
especially those with diabetes.
The FDA has recently approved several minimally invasive medical de-
- Quadrivalent influenza vaccine should be preferred to bivalent.
vices for short-term weight loss, which can be used for obesity manage- • Vaccination is contraindicated/postponed in patients with:
ment in T2DM patients.789 - Hypersensitivity to the active substances or any of the excipients of the vaccine
• At present, there are four types of FDA-regulated devices intended for - History of chicken egg allergy, particularly when considering a flu shot
- Recent history of Guillain-Barre syndrome within six weeks of previous influenza
weight loss: vaccination in the case of a flu shot
- The gastric band can be placed around the top portion of the stomach, - Postponed in patients with febrile illness or any acute infection.
thereby leaving a small amount available for food • Depending on the risk and need, other available vaccinations can be considered for
diabetes.
- Electrical stimulation systems block nerve activity between the brain
- Hepatitis
and stomach using electrical stimulators which are placed in the abdomen - Herpes
- Gastric balloon systems act by delaying gastric emptying using inflat- - HPV
able balloons placed in the stomach to utilize space. - COVID-19
- Gastric emptying systems drain food after eating with the help of a tube
that is inserted between the stomach and outside of the abdomen.
Summary
• Treating obesity is an essential and often neglected aspect of diabetes
treatment. The clinician should choose appropriate regimens to aid the
patient in weight management and thus improve the quality of care.
• There is strong and consistent evidence that in obese or overweight
patients with Type2 DM, weight management can improve glycemic
control and reduce the amount of glucose-lowering medications37-42
• There is data to suggest that intense caloric restriction and 10-15 kg
weight loss may lead to a lowering of HbA1c and, in some instances,
remission of Type 2 DM for at least two years.52
• Several glucose-lowering medications, namely the SGLT2-I and GLP1
RA, afford weight reduction and other pleiotropic benefits in addition to
glycemic management and should be an early consideration in an obese
patient with Type 2 DM.
• Metabolic surgery has been associated with significant improvement of Limited Care
type 2 DM and other co-morbidities and reduced mortality.77-81
The principles for infections and vaccinations with diabetes are recommended care subject to the
availability and affordability of pneumococcal and influenza vaccines.
Background ▪ Hepatitis A is the most common vaccine-preventable virus acquired

The risk of developing infectious diseases due to diabetes is now consid- during travel and is highly prevalent in the Indian subcontinent.
ered a significant complication of diabetes.790,791 Diabetes increases the Protection with hepatitis A vaccination is proven to last at least 15
risk of infection by two to three times compared to the non-diabetic years.808
population. The morbidity and mortality associated with infectious dis- • Data from a systematic review of 13 observational studies indicate that
eases such as influenza, pneumonia, and hepatitis, which is usually pre- efforts to diagnose, detect, and treat diabetes early may have a beneficial
ventable by appropriate vaccination, also appear to be very high in dia- impact on TB control.809
betes subjects.792 Patients with T2DM, especially those with PVD, are at
increased risk for many typical and atypical infections due to immune Types of vaccines
dysfunction, DN, and poor circulation.793 Furthermore, skin breakdown Various types of vaccinations recommended to prevent these infections
in patients with advanced diabetes and PVD provides a portal of entry for are:
bacteria. Longer duration of diabetes and poor glycemic control causes an • Pneumococcal vaccination: Two pneumococcal vaccines are available:
increased risk of pneumonia related hospitalizations in diabetes subjects PPSV23 and PCV13. Secondary immune response after PCV13 immu-
due to the compromised immune system of the host.794 A recent study nization is higher, whereas the response is lower after immunization
demonstrated that patients with high blood glucose levels are at increased with the PPSV23 vaccine.810
risk of community-acquired pneumonia.795,796 Even certain viral infec- • The panel recommends the use of PCV13 for adults ≥50 years followed
tions can lead to new onset of diabetes in the population genetically prone by a dose of PPSV23 at least 1 year later (and at least 5 years after their
to develop diabetes. previous PPSV23 dose) depending on the clinical judgment of the phy-
sician. These recommendations are in line with the guidelines from the
Considerations ADA 2017 and are also in synergy with the guidelines released recently
The decision to conduct a screening program should be based on local by the Indian Society of Nephrology 2016, Indian Academy of Allergy
factors such as limited resources and the high prevalence of diabetes- 2017, and the Geriatric Society of India 2015.811–814
related infections that were reviewed in the Indian context. • PCV13 is available for vaccination of older adults and must be consid-
ered an important step for vaccinating older diabetes patients with an
Rationale and Evidence age of >50 years. PPSV23 may be offered to immune-compromised
Infections in diabetes patients with diabetes for additional coverage after PCV13. Repeated
• Several factors have been implicated for infections in diabetes, of which vaccination with PPSV23 must be avoided to prevent hypo-responsive-
altered immunity is the most predominant one.793,797 Other predispos- ness. Clinical judgment in relation to individual subjects should be
ing factors increases susceptibility to infections include diabetes-related relied upon before these recommendations are put into practice.
complications, frequent catheterization and dialysis in chronic renal fail- • Influenza vaccination: In all patients with T2DM with age ≥6 months,
ure patients. Evidence that these immunological defects can be corrected excluding those allergic to eggs, influenza vaccine is recommend-
through reasonable glycemic control, supports the importance of close ed.815,816 Influenza vaccination among diabetes patients reduced hospi-
monitoring of infectious diseases in subjects with diabetes.798 tal admissions by 79% in two influenza epidemics in England.817
• Urinary tract, respiratory tract, foot, and deep soft infections are most • HBV: To all unvaccinated patients with diabetes of 19–59 years, three-
common in T2DM, with increased incidence and high mortality.799,800 dose series of HBV is recommended.816 In unvaccinated patients ≥ 60
• The following section deals with evidence from Indian and global stud- years of age, the three-dose series vaccine could be considered.816
ies on infections that commonly occur in patients with diabetes • Apart from the vaccines mentioned above, other routinely recommend-
ed, age-related vaccines should also be provided to all diabetes pa-
◦ Influenza: Diabetes increases the risk of hospitalization after influenza tients.816
infection and quadruples the risk of intensive care unit (ICU) admission
after hospitalization.801 Death rates among patients with diabetes during Methods to improve the rate of vaccination
influenza epidemics may increase up to 5–15%.802 Evidence that influ- • Despite the importance of vaccination in diabetes patients, vaccination
enza can trigger coronary complications, when taken in the context of rates are low. In a survey on 307 diabetes patients in Singapore, only
diabetes subjects, gains more significance since the risk for CVD is 30.6% of patients were vaccinated with the influenza vaccine.818
already 2-to 4-fold higher in this subgroup.800,803 Another cross-sectional survey on 279 diabetes patients in Spain deter-
◦ Infections of hand and upper limb: Diabetes ulcers in the upper limb mined the vaccination rates for seasonal influenza, pneumococcus, and
should be promptly treated with adequate surgical means to prevent the hepatitis B as 40%, 2%, and 2% respectively.819 A survey on 274
spreading of infection. Creating awareness of healthy cleaning practices elderly people in Turkey revealed that the proportion of diabetes pa-
minimizes disability and results in a better outcome.804 tients vaccinated for influenza or pneumococcus or tetanus was 38.1%,
◦ Hepatitis: It has been observed that several patients with underlying 13.4%, and 9.28% respectively.820
diabetes suffer from a prolonged or complicated course of acute viral • Perception, knowledge, and misconception that vaccines are infective
hepatitis. It is possible that with impaired hepatocyte regenerating ca- and cause side effects are some of the barriers to avoiding
pacity, these patients run a more prolonged and complicated course. In vaccination.818,819
the diabetes population, hepatitis B and C produces more comorbidities • Maintaining a diabetes registry, systemic tracking system, and reminder
and prolonged infections. system serve as tools for improvising the acceptance to vaccination and
communicating with the subjects for the need of vaccination which
▪ Even though the hepatitis B virus (HBV) itself may not cause diabetes provides awareness on immunization.819,821 The combined use of pa-
directly, cirrhosis derived from HBV infection poses a two-fold higher tient outreach letters, special immunization clinics, standing orders, and
risk for T2DM.805 Infection due to HBV may occur during monitoring practitioner reminders on medical records resulted in a remarkable 15
of blood glucose and other procedures involving multi-patient use of fold increase in pneumococcal vaccinations in diabetes patients in
finger stick devices designed for single-patient use and inadequate dis- Guam, United States.822 Similarly, a combination of strategies including
infection and cleaning of blood glucose monitors between patients.806 dissemination of guidelines, advice on setting up disease and vaccine
▪ When hepatitis C virus (HCV) infection occurs in diabetes patients, the registers, call and recall systems and benchmarking of performance
chronicity and the risk of infections increase. A meta-analysis of 22 remarkably improved influenza and pneumococcal vaccination rates in
studies found that patients with T2DM were at higher risk for acquiring high-risk individual groups including diabetes patients in the United
HCV than non-T2DM patients (OR: 53.50, 95% CI: 52.54, 54.82).807 Kingdom.823 Periodic training of the staff accompanied by ongoing
assessment of immunization rates and work flow and also a close follow Limited Care
up with the patient or his care giver by the treatment team is beneficial in • Adult men with diabetes should be screened with a detailed sexual function history for
minimizing the risk of inappropriate re-vaccinations.824 ED, as early as when they are diagnosed with diabetes.
• The protocols should also aim at implementing a quality assurance • Symptoms of hypogonadism including lack of interest in sex and ED should be
process to maintain the standards of care.825 investigated further with screening for serum testosterone concentration in the
morning.
• Promotion of lifestyle changes to reduce the associated risk factors should be
Implementation encouraged in men with diabetes and SD
Apart from the micro-and macro-vascular events in diabetes, infections • To identify whether a woman with diabetes has sexual dysfunction, a detailed history
due to influenza and pneumococci should be considered a significant and examination is the first step.
• Currently, the therapeutic recommendations for FSD include maintaining a
public health concern. All clinics providing vaccinations shall maintain healthy lifestyle, achieving optimal glycemic control, genitourinary infection
the records to assess the efficacy of vaccines regarding the occurrence of control, and resolving psychosocial issues.
various complications in vaccinated individuals compared to non-
vaccinated subjects. Vaccination strategies for diabetes should evolve as
part of routine care, and a central registry must be maintained. Background
Diabetes ensued vasculopathy and neuropathy have been associated with
SEXUAL DYSFUNCTION dysfunction of normal sexual function leading to psychosocial disruption
Recommendations and decreased quality of life in both men and women.827–829 Sexual
dysfunction (SD) in diabetics is a neglected aspect in India, primarily
Recommended Care due to minimal communication time between physician and patient, lack
of privacy during doctor visits and the taboo factor. In men with diabetes,
• A detailed history and examination should be conducted in an unintimidating
private setting with structured interviews by encouraging discussion regarding erectile dysfunction (ED) as a result of autonomic neuropathy is com-
sexual concerns in both men and women with diabetes. monly observed, and the prevalence odds compared with controls is more
• Appropriate language considering the patient’s age and culture should be used to make than 3.5 times.830 In a study conducted in a hospital in New Delhi, Sondhi
the patient comfortable. et al. observed the prevalence of ED to be 78.7% in men with T2DM
• Psychological and social disturbances, if any, should be discussed in an empathetic
manner.
versus 46% in non-diabetics and a significant correlation between dura-
• Promotion of lifestyle changes to reduce the associated risk factors should be tion of diabetes and ED.831 Furthermore, the Massachusetts male aging
encouraged in patients with diabetes of both sexes. study demonstrated that the risk of ED is double in aged diabetics versus
Men the general population.832 Diabetic neuropathy, impaired relaxation of
• Prolactin and TFT levels should be considered before measuring testosterone.
cavernosal smooth muscle due to altered cyclic guanosine
• Testosterone levels should ideally be recorded in a good NABL lab, and should be
done before 11 am, repeated if it is low. CBC PSA should be monitored thoroughly. monophosphate/nitric oxide pathway and risk of decreased testosterone
• Patients should be made to understand the difference between erectile dysfunction and levels resulting from hypogonadism can constitute the underlying pathol-
premature ejaculation. ogy of ED.833,834 Other sexual complications in men with diabetes in-
• Adult men with diabetes should be screened with a detailed sexual function history for clude ejaculatory dysfunction and hypogonadism. The recent ADA
ED as early as they are diagnosed with diabetes. Sexual history has to be taken during
the first visit, along with the study of the frequency of sexual dynamics.
guideline recommends testing for serum testosterone concentration in
• Detection of ED and evaluation of the response to treatment should be performed by men with diabetes who have symptoms of hypogonadism.835
validated questionnaires such as IIEF or Sexual Health Inventory for men. Compared with men, SD in women with diabetes is rarely investigated
• PDE-5 inhibitors should be given based on the sexual frequency of the patient and and often untreated. In countries like India, where gender inequality and
may be offered as first-line therapy for the treatment of ED in men with diabetes as
they improve the quality of life of the patients and are associated with low side effects.
the cultural disparity are high, management strategies for tackling such
• Symptoms of hypogonadism, including lack of interest in sex and ED should be health concerns are almost nonexistent.836 However, the findings of a
investigated further with screening for serum testosterone concentration in the meta-analysis showed that the risk of female sexual dysfunction (FSD)
morning. Testosterone replacement may be beneficial in men with diabetes with was two times higher (OR [95%CI], 2.02 [1.49, 2.72]) and correlated with
symptomatic hypogonadism.
a low Female Sexual Function Index (FSFI) score in women with diabe-
• Since psychogenic and organic components are also broadly responsible for ED,
counselling should be recommended. tes as compared with non-diabetics.837 FSD is an intricate condition in-
Women volving both physiological and psychosocial changes. It includes
• To identify whether a woman with diabetes has sexual dysfunction, eliciting a detailed hypoactive sexual desire disorder, arousal and lubrication disorder, pain
history in a compassionate manner and examination is the first step. during sexual intercourse, and loss of ability to achieve orgasm.838
• Several self-reported validated questionnaires such as Female Sexual Function Index,
the Female Sexual Distress (FSD) Scale, the Brief Index of Sexual Functioning for
Hyperglycemia decreases the hydration of the vaginal mucosa and lubri-
Women, and the Derogates Interview for Sexual Function have been developed to cation of the vagina and is the cause of genitourinary infections and
assess FSD. dyspareunia. The vascular complications and endothelial dysfunction
• Post-menopausal women with diabetes are prone to have a low desire or depression826 may impact blood supply to the clitoris and lead to poor lubrication of
and, mental health check-ups are recommended to rule out or manage the symptoms.
• Postmenopausal women, particularly those in the middle-age range, should be
the vagina and reduced arousal and dyspareunia.827 Diabetic neuropathy
assessed for CV risk factors and FSD, so that both CVDs and sexual problems do not may cause structural and functional changes in the female genitalia and
persist unnoticed. can disrupt the balance between receiving sexual stimuli and sexual re-
• Currently, the therapeutic recommendations for FSD include maintaining a sponse triggers. Hormonal imbalances in levels of estrogen and andro-
healthy lifestyle, achieving an optimal glycemic control, genitourinary infection
gens can lead to FSD in women with diabetes. In a study from North India
control, and resolving psychosocial issues., And of course, Genitourinary
hygiene. conducted on women with diabetes, it was observed that 45.19%
• Treatment with water-based vaginal lubricants, hormone replacement therapy, clitoral complained of desire disorder, 62.71% of arousal disorder, 84.75% of
therapy device, and genital infection control therapy is recommended. orgasmic disorder and 20.38% experienced pain disorder; the incidence
• Treatment strategies with dehydroepiandrosterone supplementation, estrogen or of these disorders was higher in older women.839
androgen replacement, flibanserin (serotonin 1A receptor agonist and a serotonin 2A
receptor antagonist), and PDE-5 inhibitors are investigated; however, currently there
is limited evidence for their use. Considerations
Gender, glycemic control, comorbidities, lifestyle management and
knowledge of sexual disorders and their management, cultural environ-
ment, psychological disorders, and counselling should be considered
when framing these recommendations for sexual dysfunction in patients
with diabetes.
Rationale and Evidence their health care professionals (HCPs). Moreover, midlife women are
Men typically unaware or have misconceptions about conditions that may
• Longer duration of diabetes is considered a risk for ED.831 adversely impact their sexual life, such as genitourinary syndrome of
• Commonly associated comorbidities of diabetes including metabolic menopause and hypoactive sexual desire disorder. Without understand-
syndrome, obesity, hyperlipidemia, hypertension and autonomic neu- ing there may be underlying medical conditions, there is also a lack of
ropathy are also considered as risk factors of ED.840 awareness about the fact that safe and effective treatments are available.
• Anti-hypertensives, antidepressants and fibrates are frequent concomi- 850,853
tant medications consumed by patients having diabetes and these are • According to the data of “The Prevalence of Female Sexual Problems
associated with increased risks of ED.841 Associated with Distress and Determinants of Treatment Seeking
• A significant association between ED and cardiovascular events, all- (PRESIDE) study”, involving 31,581 US women, sexual problems (de-
cause mortality, CHD and stroke has been reported in several studies.842 sire, arousal, and orgasm) affect 43.1% of women. Hypoactive sexual
Meena et al. observed an increased cardiovascular risk in patients with desire is the most common dysfunction reported by 39% of women, low
T2DM and ED without overt cardiovascular disease (CVD) in compar- arousal by 26%, and orgasm problems by 21%.854 In Europe, the
ison to patients without ED (34.87 ± 18.82 vs 20.91 ± 11.03 p = “Women’s International Sexuality and Health Survey” (WISHeS), con-
0.002).843 ducted in 1356 women from Germany, United Kingdom, France, and
• Below normal testosterone concentrations and higher rates of Italy, reported a prevalence of FSD in 29% of women.855
hypogonadism have been reported in men with diabetes as compared • Sexual disorders in female patients with type 2 diabetes demonstrate the
with the general population.844 Testosterone regulates normal erectile correlation with the occurrence of depression and the acceptance of their
functioning and, evidence from studies suggests the use of testosterone illness. Sexual disorders in diabetic patients occur more frequently in
replacement in patients with diabetes and symptomatic older women and in those with a longer duration of diabetes.856
hypogonadism.845 In a cross-sectional study conducted in India, the
prevalence of hypogonadism was found to be 20.7%in T2DM In a study, 756 Adults with diabetes completed an online survey includ-
patients.846 ing questions on sexual functioning (adapted Short Sexual Functional
• Men with hypogonadism do not respond optimally to phosphodiesterase Scale), general emotional well-being (WHO-5), symptoms of anxiety
type (PDE)-5 inhibitors and in such patients, testosterone replacement (GAD-7) and diabetes distress (PAID-20). One third of participants re-
was observed to be effective in 50% of patients.845 ported a sexual dysfunction. Men reported erectile dysfunction (T1D:
• Whether glycemic control has any effect on the reduction of ED risk is 20%; T2D: 33%), and orgasmic dysfunction (T1D: 22%; T2D: 27%).
unclear as studies have shown contrasting results. However, intensive In men, sexual dysfunction was independently associated with, older
lifestyle changes ameliorated ED worsening and improved the overall age (OR = 1.05, p = 0.022), higher waist circumference (OR =
International Index of Erectile Function (IIEF) score in overweight men 1.04; p < 0.001) and longer duration of diabetes (OR = 1.04; p =
with diabetes compared with controls in the LOOK AHEAD study.847 0.007). More men with sexual dysfunction reported diabetes distress
• Men with T2DM and severe ED were found to have poor glycemic (20% vs. 12%, p = 0.026). Women reported decreased desire (T1D:
control, longer duration of untreated diabetes, later age of onset and 22%; T2D: 15%) and decreased arousal (T1D: 9%; T2D: 11%). More
poor quality of life.848 women with sexual dysfunction reported diabetes distress (36% vs.
• The ongoing TRAVERSE Trail findings will implicate determining the 21%, p = 0.003), impaired emotional well-being (36% vs. 25%, p =
CV safety and long-term efficacy of testosterone treatment in middle- 0.036) and anxiety symptoms (20% vs. 11%, p = 0.026).857
aged and older men with hypogonadism with or at increased risk of CV
disease.849 Implementations
• Ejaculatory dysfunction (EjD) constitutes significant sexual sequelae in Normal sexual function is essential for the holistic well-being of an indi-
diabetic men, with up to 35-50% of men with DM suffering from EjD. vidual. Diabetes with its ever-increasing prevalence is a cause of sexual
The main disorders of ejaculation include premature ejaculation (PE), dysfunction in both men and women. The vascular and neurological
delayed ejaculation (DE), anejaculation (AE) and retrograde ejaculation complications induced by diabetes constitute the underlying pathogenesis
(RE). Whilst promising findings from large randomized controlled trials of these sexual dysfunctions. Association of diabetes with obesity, meta-
(RCTs) have provided strong evidence for the licensed treatment of PE, bolic syndrome, hypertension, dyslipidemia and CVD are considered as
similar robust studies are needed to accurately elucidate factors risk factors for ED. The diagnosis of ED predicts further investigation of
predicting EjD in DM, as well as for the development of pharmacother- CV events in men with diabetes. Furthermore, symptoms of
apies for DE and RE.850,851 hypogonadism should be investigated by assessing the serum testosterone
concentrations. A detailed history of FSD obtained in a compassionate
Women and structured method is essential in women with diabetes. Although,
• Diabetes-induced neuropathy and vascular dysfunction may be mainly limited evidence exists to show correlation between FSD and CV events,
responsible for the FSD and the low Female Sexual Function Index may lifestyle modifications, glycemic control, care of genetic infections and
be associated with BMI.[670] resolution of psychosocial factors should be discussed and emphasized.
• Higher risk of FSD was observed in premenopausal as compared to It becomes clinically relevant to assess particularly postmenopausal wom-
postmenopausal women with diabetes. en for FSD and CVDs, since both disorders still remain underdiagnosed
• The risk factors associated with FSD include age, obesity, dyslipidemia, and sub-optimally untreated. Clitoral Doppler ultrasound could represent
CVD, complications of diabetes, depression and marital status.828,852 a useful technique to diagnose the presence of underlying CVD, which
• Based on the current evidence, a clear correlation between FSD and along with risk factors could predict sexual dysfunction in women.
CVD has not been established unlike in men with diabetes. A mention about possible relationship between CV disease and ED in
• In women, psychological and psychosocial factors contribute to FSD men having T2DM will be justified based on robust evidence necessitat-
more than in men. ing CV risk assessment and/or screening for ASCVD in male patients
• Social stigma around female sexuality remains and as a result, women having T2DM and ED.
often avoid and/or are embarrassed to discuss their sexual health with
CLINICAL MONITORING SMBG is an essential component of modern diabetes treatment; it is the

RECOMMENDATIONS most straightforward and possibly most practical tool to assess the effi-
cacy and safety of glycemic control.851,862 SMBG facilitates patients
Recommended Care and healthcare providers to adjust their therapeutic regimen in response to
blood glucose values and regulate their dietary intake, physical activity,
• Monitor blood glucose control by measuring HbA1c using high-precision methods and insulin doses to improve glycemic control regularly.858,863
standardized and aligned to the international reference values.
• Self- Monitoring Blood Glucose (SMBG) enables patients to confirm symptomatic
Established advantages with SMBG include achieving target HbA1c,
hypoglycemia and detect asymptomatic hypoglycemia and glucose variability. It reducing glucose variability, and predicting severe hypoglycemia.863
facilitates making appropriate adjustments in treatment medications and nutrition SMBG complements HbA1c testing as it can differentiate the fasting,
therapy to achieve HbA1c targets and prevent hypoglycemia. pre-prandial, and post-prandial hyperglycemic levels, detect the glycemic
• In patients on insulin, a combination of HbA1c and SMBG helps achieve glycemic
excursions, recognize and contribute to monitoring and resolution of hy-
control.
• Measure HbA1c every three to six months depending on level, stability of blood poglycemia, and provide immediate feedback to patients about the effects
glucose control, and changes in therapy and report HbA1c results in percentages. of food choices, activity, and medication on glycemic control.864
• Advise individuals with diabetes that maintaining an HbA1c <7.0% minimizes the The International Diabetes Federation (IDF) and American Diabetes
risk of developing complications. Association (ADA) recommend SMBG as an integral component of ef-
• A lower value of the HbA1c target may be considered if it is quickly and safely
achieved without hypoglycemia.
fective T2DM management.7,857 Despite substantial evidence of the
• A higher value of the HbA1c target may be considered for individuals where benefits of SMBG, compliance to self-monitoring is reported “low” glob-
previous attempts to optimize control were associated with unacceptable ally,865 particularly in developing countries like India, where patients
hypoglycemia or in those individuals who are at a higher risk for hypoglycemia. usually seek treatment after complications have set in. This may be at-
• Treatment should be reviewed and modified if the HbA1c level exceeds the agreed
tributed to a lack of awareness, literacy levels, and perception that SMBG
target on two consecutive occasions.
• Advise those who target HbA1c levels cannot be reached that any improvement is
is painful and costly.866
beneficial. CGM has fulfilled an unmet need in diabetes care by providing an option
• Anemia must be excluded before a proper diagnosis based on HbA1c values is of automated glucose monitoring, which may help improve glucose con-
made. Anemia and abnormal hemoglobin may affect the values obtained for HbA1c trol in patients with uncontrolled T2DM and patients on acute and inten-
in some assays. To determine whether abnormal hemoglobin is present, use high-
sive glucose lowering regimens. The current recommendations provide
performance liquid chromatography or mass spectrometry. In individuals with
hemoglobinopathies, fructosamine may be used as a surrogate. insight into the importance and frequency of monitoring to facilitate med-
• Point-of-care capillary blood glucose meters should be used to measure blood ication and lifestyle changes when average HbA1c values remain above
glucose when patients are hospitalized. Blood glucose meters conforming to the target levels.
latest ISO standards should be used.
• When prescribing continuous glucose monitoring or ambulatory glucose profile
(CGM/AGP), robust diabetes education, training, and support are required for
Recommendations for Glycosylated hemoglobin for monitoring
optimal continuous glucose monitor implementation and ongoing use. blood glucose:
• Regular monitoring of HbA1c will facilitate the identification of patients

with poor glycemic control and help physicians and patients to take the
Limited Care necessary steps to achieve desired glycemic targets867,868 Though
frequent monitoring of HbA1c is associated with reduced diabetes-
• If HbA1c measurement is unavailable, blood glucose should be measured either at related complications and improved metabolic control,868,869 most
point-of-care or in the laboratory.
patients do not understand or are unaware of the importance of glycemic
• In limited resource settings, diabetes control may need to be based on measuring
monitoring. Therefore, it is vital to educate patients and improve their
plasma glucose levels alone.
understanding of HbA1c levels for optimal glycemic control. 868,870
• The concept of estimated average glucose (eAG) was introduced fol-
Background lowing continuous ambulatory blood glucose monitoring.871The eAG
Monitoring the glycemic status is critical to ensure optimum glycemic may help people with diabetes relate their HbA1c to daily glucose
control. It is a cornerstone of diabetes care that may help physicians to monitoring and highlight any inaccuracies in HbA1c measurement rel-
adjust the treatment regime according to patients' needs and allow patients ative to glucose levels.872 Calculators are available for converting
to follow the prescribed diabetes care.850 Glycated hemoglobin HbA1c to eAG in both mmol/L and mg/dL. Measurement of glucose
(HbA1c), which assesses the glycosylation of the hemoglobin to an esti- levels, before meals, after meals, and fasted state are often recommend-
mated level of blood glucose over the previous three months, and self- ed as a substitute for HbA1c when the latter is unavailable or
monitoring of blood glucose (SMBG), which records the day-to-day inappropriate.
blood glucose levels, are the two most essential tools for monitoring of • Abnormal hemoglobin levels are known to affect HbA1c values in a
glycemic control.851 Measurement of HbA1c is a gold standard ap- way that can significantly alter the results concerning diabetes con-
proach for monitoring diabetes in research and clinical settings.852–854 trol.873 Therefore; it is crucial to consider hematological factors that
Most guidelines recommend clinicians must perform HbA1c measure- can confound HbA1c levels in people with diabetes; best detected using
ments routinely in all patients with T2DM as a part of continuing HPLC-based assays or measuring surrogates like Fructosamine.
care.855,856 Long-term hyperglycemia, as measured by HbA1C, is as- • Anemia significantly impacts HbA1c levels. In a cross-sectional study,
sociated with a higher risk of secondary macro-and microvascular com- the mean HbA1c in patients with controlled diabetes with Iron
plications of diabetes.857,858 Patients with diabetes who do not reach Deficiency Anemia (IDA) was considerably higher than in those with-
appropriate glycemic targets or are at an increased risk of developing out IDA (7.86 ± 0.11% vs. 5.45 ± 0.038% [p<0.05]) and the HbA1c
complications require more intensive monitoring. Further, in Asian coun- values were inversely proportional to total hemoglobin (p<0.05).874
tries like India, cultural aspects of weekly fasts, festivals, a diet rich in • Further, significantly higher HbA1c levels are observed in patients with
carbohydrates, and reluctance to change dietary habits further support the IDA than in healthy individuals (5.51 ± 0.696 v/s 4.85 ± 0.461%,
need for regular glucose monitoring. Frequent SMBG,852,858 continu- p<0.001), and the HbA1c levels significantly decline following iron
ous glucose monitoring (CGM), 859,860 assessing impending glucose supplementation (p<0.001).10 Therefore, HbA1c results in diabetes pa-
excursions (hypoglycemia and hyperglycemia), and glycemic variabili- tients with IDA should be interpreted carefully. Ideally, IDA has to be
ty861 are some of the methods of intensive glucose monitoring. corrected before a proper diagnosis is made.
• Measuring blood glucose using blood glucose meters on admission to • In elderly patients, the frequency of SMBG should be once daily (dif-
hospital wards help identify patients with hypoglycemia or hyperglyce- ferent times each day) in the initiation phase, and later it should be
mia. Considering that in developing nations like India, where cost is a reduced further to two to three times per week.
significant barrier to monitoring, these devices should be accurate and Considerations
cost-effective and field testing tailored explicitly for Asian and Indian The decisions on clinical monitoring of glycemic levels in T2DM patients
needs is imperative.875 were based on local factors such as the availability of newer technologies
• A study that assessed knowledge and attitude towards self- and the cost of monitoring that were reviewed in the Indian context
monitoring and the impact of SMBG on glycemic control re- (Table 26).
vealed that patients who monitored ≥3 times had significantly
better glycemic control of HbA1c (7.1–8%) than those who Rationale and Evidence
monitored <3 times (p=0.021).876 Insulin self-titration interven- Table 22: Recommended care for frequency/timing of SMBG 851
tions based on structured SMBG are associated with a signifi-
cant reduction in HbA1c during a follow-up of 12 weeks with a
T2DM on OADs T2DM on insulin or insulin + OADs
trend towards greater effectiveness in improving glycemic con-
trol than conventional treatment, with no increase in the inci-
New New
dence of hypoglycemia or body weight gain.877 Comparative onset/uncontrolled/
Stable/well-
onset/uncontrolled/
Stable/well-
controlled controlled
studies in patients with T2DM on insulin across cohorts of during acute illness during acute illness
regular SMBG users versus SMBG non-users have demonstrated
Paired testing at
that HbA1c levels in regular SMBG users were lower by 0.7- least 3-4 days in a
1.1%.865,878–880 week (1 day/ week
Patients on SU or At least four
pre- and post-
meglitinides: At least tests in a week
Target values for glucose control for HbA1c and capillary blood glucose At least four breakfast, one
four times/day and on four
times/day and should day/week pre- and
for diabetes, as described by the IDF 2017, are as follows881[Table 21]. should include pre- consecutive
include pre-prandial post-lunch, and one
prandial and days or
and bedtime levels. day/week pre- and
bedtime levels. alternate days
Table 21: Target values for glucose control for glycosylated hemo- Must check whenever post-dinner) or as
Patients on other (including an
globin in non-pregnant adults OADs: FBG and three
hypoglycemia is frequently as
suspected. possible.
At least FBG on postprandial
Must check
Targets Targets, if possible, to alternate days. values).
whenever
achieve without
hypoglycemia is
causing hypoglycemia.
suspected.
HbA1c (%) <7.0 <6.5
FBG: Fasting plasma glucose, OADs: Oral antidiabetics, SU: Sulphonylureas, DM:
Diabetes mellitus, T2DM: Type 2 DM
Fasting Blood 115 <100
Glucose(mg/dL)
Post-prandial blood glucose 160 <140 Those who drive must measure sugar before the start of the journey to
(mg/dL) ensure it’s more than 90 mg/dl and preferably every 2 hours after that
DM: Diabetes mellitus, FPG: Fasting plasma glucose, during the trip. Periodic carbohydrate snacking is recommended. To stop
HbA1c: Glycosylated hemoglobin, IGT: Impaired glucose tolerance, PPG: Postprandial the car engine, take out the keys and move to the non-driver’s seat if they
glucose, T2DM: Type 2 DM
feel hypoglycemic, measure blood sugar, and if it’s below 90 mg/dl, to
have simple carbohydrates. Not to drive for at least 45 minutes after
Recommendations for self-monitoring of blood glucose [Tables 22 - 25] recovery. Anyone who is an Insulin user or on drugs that are known to
• Selecting a structured, flexible SMBG pattern that can be tailored to the cause hypoglycemia like Sulfonylureas or meglitinides should record
clinical, educational, behavioral, and financial requirements of individ- their blood glucose on a glucometer which has memory and can store
uals with diabetes is recommended.851 It is essential to determine the readings for up to last three months (to be reviewed by the physician).
frequency and intensity of SMBG needed to support the chosen treat-
ment regimen. One should also consider practical obstacles to monitor- Table 23: Recommended care for frequency/timing of self-
ing, such as affordability or access, individualize glycemic targets and monitoring of blood glucose for diabetes in pregnancy 851
modify monitoring patterns accordingly.882,883
• Individuals with insulin-treated diabetes should be advised to perform Patients on lifestyle modifications Patients on OADs or insulin
SMBG daily, failing which, at least weekly monitoring should be en-
couraged. Pre-meal SMBGs help guide the prandial insulin dose. A day profile once a week-FBG and three
At least four times/day (FBG and three
postprandial values at least once a week or
Fasting blood glucose readings help guide the basal insulin dose. Ideal staggered over the week.
postprandial values).
SMBG: six to seven tests/day, i.e., three before and three after each meal
every day and periodically, one additional test at 3 am.851 FBG: Fasting plasma glucose, OADs: Oral antidiabetics
• In addition, SMBGs in motivated patients may help identify and correct
dietary preferences. Monitoring and documenting diet patterns and
SMBG recordings may be recommended in such cases. Plasma Glucose measurement in laboratories: Plasma glucose is the most
• Pregnant women on lifestyle modifications should have a daily profile preferred measure in most modern laboratories. Readings based on whole
weekly. This should include one fasting and three post-prandial values blood measurements are lower due to the volume occupied by hemoglo-
at least once a week or staggered over a week. 851 bin. Capillary blood glucose strips measure the glucose in the plasma of
• Pregnant women with diabetes who are on insulin may need to monitor the capillary blood sample. Still, they may be calibrated to give results as
their blood glucose more frequently, i.e., 4-6 times/day. plasma or whole blood glucose (check meter instructions).
• In patients with pre-existing diabetes or GDM, target blood glucose
levels should be 70 to 90 mg/dL fasting, <140 mg/dL 1-h post-prandial, Recommendations for Continuous glucose monitoring
and <120 mg/dL 2-h post-prandial. The recent availability of retrospective and real-time continuous glucose
monitors has opened a new dimension to diabetes care. In affording
patients who can afford technology, CGMs can improve diabetes care by Table 25: Limited care for frequency/timing of self-monitoring of
achieving glycemic targets by identifying and implementing measures to blood glucose
avoid glycemic excursions.
In exceptional cases such as pregnant women, patients on multiple daily New onset/uncontrolled/DM
Stable/well-controlled
insulin doses, and children and adolescents, CGM may help adjust pran- during acute illness
dial insulin doses and other dietary decisions.884 with the convenience of Patients on SU or meglitinides: At least
avoiding finger pricks. At least four tests in a month-at least
T2DM on FBG alternate days.
1 test/week (including an FBG and
• Garg et al. have demonstrated an improvement in glycaemic excursion OADs Patients on other: Ideally, at least FBG
three postprandial values in a month).
in insulin-treated T2DM patients using Real time-CGM, showing a sig- once a week.
nificant reduction of the time spent in the hypo- and hyper-glycaemic At least one value on alternate days
T2DM on
range with an increased time spent in the target glucose range as well as insulin or
At least FBG and one more pre-prandial at different times of the day, with at
a significant reduction of nocturnal hypoglycemia in the Real time-CGM value every day. Must check whenever least one FBG every week.
insulin +
hypoglycemia is suspected. Must check whenever hypoglycemia
group.880 OADs
is suspected.
• Mohan et al., evaluating the use of retrospective CGM, concluded that it
could effectively help healthcare professionals with insights for initiating
changes to treatment regimens, diet, and exercise behaviors and provided Patients on lifestyle modifications Patients on OADs or insulin
patients with improved knowledge of the importance of therapy compli-
ance by demonstrable reductions in HbA1c.885 Paired testing every day (pre- and
• A retrospective analysis based on a blinded study of glycaemic control post-breakfast on 1st day, pre- and
in 296 T2DM adults using masked professional CGM (P-CGM) revealed post-lunch on 2nd day, pre- and post-
One FBG and one postprandial value
Diabetes in dinner on 3rd day, and then keep
that the predominant pattern of hyperglycemia was postprandial while every week (any meal, preferably the
pregnancy repeating the cycle).
previously unknown hypoglycemia was found in 38% of the patients; largest meal of the day).
Post-delivery, an FBG and HBA1c
over half of the cases were nocturnal. The mean HbA1c of the P-CGM are recommended for all GDM
group significantly dropped at six months from baseline (P < 0.0001). patients.
The frequency of performing SMBG was also found to be substantially Patients on
In resource-limited settings, fasting levels can be performed twice a week or
increased. P-CGM motivated the patients for diabetes self-care practices, basal
once in 3 days.
improving glycaemic control over a wide range of baseline therapies.886 insulin
In resource-limited settings, given the high cost, the use of the CGM DM: Diabetes mellitus, FBG: Fasting blood glucose, OADs: Oral antidiabetics, SU:
devices is compromised till the date of publication of this document. Sulphonylureas, T2DM: Type 2 DM
Implementations
There should be access to a laboratory or site-of-care test monitored by Table 26: Other aspects of clinical monitoring
certified quality assurance schemes to measure HbA1c. In instances
where HbA1c measurement is inappropriate, such individuals must be Type of Recommended care Limited care
monitoring
identified by carefully reviewing hematological parameters and other
factors affecting HbA1c values. The provision of capillary blood glucose Complete history A complete history (including- presenting As for recommended care.
meters and strips must be assured in hospitals and clinics. It is vital to and physical complaints, medical conditions, diet,
examination lifestyle, habits, family, medication, and
ascertain whether there are contraindications to using a particular type of physical examination is recommended
glucose meter for a specific patient. It is essential to establish whether Periodicity: At diagnosis or first visit and
glucose meters report values for plasma or blood and to ensure that then Annually.
schemes for monitoring the quality of their output are in place. Blood
Anthropometry Weight, waist circumference/BMI
glucose meters should be calibrated regularly, used in hospitals, and re-
stricted to trained personnel.
Ophthalmic Detailed exam by a qualified Patients are to be referred to
Table 24: Recommendations for glycemic targets in people who are ophthalmologist or fundus photographs ophthalmologists if
prone to develop Hypoglycemia (associated with Renal, Hepatic, or (with in-person or AI-based interpretation retinopathy is suspected.
CVD risks) 882,883 by skilled ophthalmologists).
Periodicity: At diagnosis and every two
years if there is no retinopathy
Target glycemic levels Patients on Patients with Patients
Reasons for:
hypoglycemic intermediate with poor
Immediate referral:
agents health status health
status Rubeosis iridis/neovascular
glaucoma
HbA1c (%) < 7.5 < 8.0 < 8.0 Vitreous hemorrhage
Advanced retinopathy with retinal
Fasting or pre-prandial 90-130 65 100-150 detachment
glucose (mg/dL) Urgent Referral: (<2 weeks)
R3/Proliferative retinopathy
Bedtime glucose (mg/dL) 90-150 150-180 150-220
Routine referral: (<13 weeks)
R2/Pre-proliferative changes
HbA1c: Glycosylated
M1/Maculopathy
hemoglobin
Routine non-DR referral:
Cataracts
Other categories;
R0/No retinopathy-annual
screening, moving to 2 years if two
negative screens.
TECHNOLOGIES
Recommendations
R1/background retinopathy-annual
Recommended Care
screening and inform diabetes care
team.
Continuous glucose monitoring (CGM)
Smoking cessation As for recommended care • CGM should be considered in conjunction with SMBG and HbA1C for glycemic status
assessment in those T2DM individuals treated with intensive insulin therapy and who are
Alcohol Counseling for moderation As recommended for care not achieving glucose targets.895
• Two types of CGMs are available. The professional or retrospective (blinded) CGM which
BP measurement BP measurement at each visit As for recommended care records the data that can be downloaded later in a physician’s office and the personal or
prospective (Real-time) CGM which displays the interstitial glucose values with continuous
Measurement of At diagnosis or age 40 years and At diagnosis or age 40 basis.
lipids periodically (6 monthly) after that years, at least
• CGMs can be a helpful tool in diabetes education by facilitating effective communication
Screening for A resting ECG may provide helpful As for recommended care between clinicians and patients. All users should get trained on how to interpret and respond
CVD information on baseline cardiac status to their glucose data.896
and (for future reference) 2d ECHO when • AGP Report along with %TIR, %TBR, %TAR, and daily glucose pattern may be used for
required education and motivation of patients living with diabetes.897
• 14 days of CGM is required for the assessment of Time in the Range of which at least 70%
Microalbuminuria At diagnosis, after correcting glycemia If resources are limited and
of the data should be available.
and achieving BP Goals, and annually technical issues may
• In well-controlled T2DM, professional CGM once in 6 months could be sufficient
after that. consider using ACEI/ARB.
irrespective of the treatment regimen. If the %TIR is low or %TBR is significantly high then
If BP is >140/80 Dipsticks CGM may be repeated more frequently based on the clinical judgment and availability of
for MA can be used. resources.898
Every patient’s urine should • CGM may be considered in women with GDM or pregnant women with T2DM
be examined routinely and and as a supplemental tool to SMBG in individuals with hypoglycemia
microscopically. unawareness and/or frequent hypoglycemic episodes.
• Only CGM systems with an acceptable level of sensor accuracy should be used and when
Distal peripheral At diagnosis and at least annually As recommended by IDF, assessing hypoglycemia, the accuracy of the CGM data in the lower glycemic range
neuropathy Test for vibration with a 128 Hz tuning Additional training is should be considered and hypoglycemia conformed by SMBG where needed.
fork or a 10 g monofilament, or with required.
Continuous subcutaneous insulin infusion (CSII) or insulin pump therapy
Biothesiometer or Neurothesiometer
• CSII or insulin pump therapy may be considered in pediatric patients or in adults
(VPT) along with pinprick sensation and
on ≥4 insulin injections per day (intensively managed insulin-dependent T2DM).
ankle jerk.
Peripheral arterial At diagnosis As for recommended care Common indications are:

disease History of claudication, distal pulses, and Additional training required • High HbA1C levels despite MDI
ABI, Foot doppler. • Recurrent episodes of hypoglycemia or hypoglycemia unawareness
• Patients on high doses of insulin or poor glycemic control despite intensive therapy
Comprehensive At diagnosis and annually. As for recommended care, • Presence of or future risk of diabetes-related complications, or recurrent DKA/recurrent
foot care Assessment of foot pulses and testing for Additional training is hospitalizations
loss of protective sensation (10 g required. • Dawn phenomenon
monofilament plus testing any one of • Glycemic variability causing challenges in diabetes management
Vibration using 128 Hz tuning fork, • Unpredictable food or meal intake patterns
pinprick sensation, ankle reflexes, or • Patients seeking improved quality of life
vibration perception threshold). • Insulin pump therapy seems to be safe and effective for maintaining glycemic control and
Look for calluses, ulcers, and foot for better outcomes in pregnancies complicated by GDM/ T2DM and requiring large
deformities. insulin doses. However, it is not recommended as a part of routine practice.
• During hospital admissions, CSII is not recommended in critically ill patients if the
BP: Blood pressure, CV: Cardiovascular, CVD: CV disease, ECG: Electrocardiogram, ABI: hospital/ICU staff is not familiar with the device
Ankle-brachial index, ACEI: Angiotensin-converting enzyme, • In non-critically ill patients, continued use of CSII is recommended if the patient can
ARB: Angiotensin receptor blocker, IDF: International Diabetes Federation manage the use of the device himself or has trained assistance for the same.
• CSII should be prescribed to only those eligible patients who are willing and motivated
to monitor glucose levels at least four times a day, quantify food intake, and comply with
follow-up. Patients must be psychologically stable and in the case of young candidates,
they should have adequate support from motivated caregivers who can learn and can
commit to the different aspects of diabetes management.
• CSII should only be initiated at a well-equipped center that has trained resources to initiate
and follow up the patients on CSII or centers willing to acquire the training and expertise.
• AID: Automated Insulin Delivery devices such as 780G though very expensive may be used
in eligible subjects, for automating both basal and bolus insulin delivery based on sensor
glucose levels.
• Continuous training and retraining would be required to learn
the techniques and excel in CSII management.
• Change of cannula insertion site as per manufacturer’s label
should be recommended.
Clinical decision support tools and diabetes management platforms

• Technologies that aid patients and/or healthcare providers in the diagnosis and management
of diabetes can improve both the short-term and long-term disease outcomes.
• Adequate training needs to be provided to the healthcare professionals in using the clinical
decision support tools and diabetes management platforms.
• From among the various diabetes self-management tools and platforms available, patients
must be encouraged to adopt the most appropriate tool that would best suit their disease
needs and lifestyle.
Patients must be encouraged to seek timely guidance and frequent reassessment from a trained
healthcare team and must be made aware that the adoption of various diabetes self-management
tools does not diminish the importance of the former.
Table 27: Recommendations on the technologies suggested for rec- diabetes should be trained and encourages to use the glucose meter reg-
ommended care and limited care ularly through the frequency may differ based on individual needs, nature
of therapy, available resources and glucose profiles.
Technology Recommended Care Limited Care
Continuous glucose monitoring systems
Glucose meter Yes Yes All CGM systems have one goal: providing glucose monitoring data for
(SMBG) optimizing lifestyle interventions and pharmacotherapies for preventing
Diabetes Apps Yes Yes blood glucose variations also measures interstitial fluid glucose and CGM
system involves using devices and sensors attached to a body part (arm/
Insulin pump Yes; indications should Can be discussed
be discussed and apart when there is a abdomen) with a variable life of 7-14 days. This may also require cali-
from usual indications, compelling bration of using an SMBG device.
CSII as an option to indication
improve the quality of
life of the individual Types of CGMS devices
should be discussed.
• Retrospective systems that measure the glucose concentration during a
CGM Yes; indications should be Can be discussed certain time span: The information stored in the sensor can be
discussed where affordability
is not an issue. downloaded using a monitor. They first record the glucose levels, pro-
viding retrospective information of the overall glycemic profile, without
a RT display of glycemic value. In fact, it allows to evaluate the glyce-
mic profile in patients with poorly controlled diabetes, detecting and
Background
preventing unrecognized hypoglycemic events, identifying glycemic
Technology has gradually become indispensable in the management of
patterns and trends which permit changes in pharmacotherapy with
diabetes. Various different technologies are now being routinely used for
physical and dietary interventions.
monitoring, drug delivery, improving clinical decision support, compli-
• Real Time systems that continuously provide the actual glucose con-
ance and adhere to lifestyle changes and therapy.
centration on a display: RT monitoring shows directly to the patient the
Continuous glucose monitoring (CGMs) and Continuous subcutaneous
glucose levels in RT. It may provide alarms when glucose values in case
insulin-pump infusions (Insulin pumps) have limited reach yet in India,
of extremes at pre-defined preset values to prevent severe hyper and
but glucose meters (SMBG), telemedicine and mobile apps may be
hypoglycemia frequency. Some of the RT systems may require inter-
cheaper options for enhancing adherence to therapy, enable coaching
mittent scanning of sensor (min once in 8 hours) to be able to record and
with an aim to improve metabolic outcomes and reach goals of
display the RT data on a continuous basis (isCGM- intermittent CGM).
management.
There have been a few guidelines, consensus and recommendations both
Recommendations for CGMS
internationally, as well as specific to Indian scenario regarding the use of
1. Clinical situations that may require greater glucose monitoring
various technologies, its use and limitations, its merits and challenges,
accuracy
and guidance on recommended care and limited care in resources restrict-
- History of severe hypoglycemia
ed situations, all aimed at improving lives of people with diabetes and
- Hypoglycemia unawareness
preventing complications of diabetes.
- Pregnancy
- Infants and children receiving insulin therapy
- Patients at risk for hypoglycemia, including patients receiving basal
Blood glucose meters
insulin
SMBG with a quality glucose meter has been proven to be useful at any
- Patients receiving basal-bolus insulin therapy with multiple injections
stage of diabetes provided a structured SMBG protocol is implemented
per day
with the patient-centered approach. Glucose monitoring, particularly
- Patients receiving sulfonylureas or glinides (insulin secretagogues)
SMBG is considered as an integral part of diabetes care899–902 since
- Patients with irregular schedules skipped or small meals, vigorous ex-
achieving optimal glycemic control has been proven to be associated with
ercise, travel between time zones, disrupted sleep schedules, shift work
reductions in both macro-and microvascular complications of the dis-
- People with occupational risks that enhance possible risks from hypo-
ease.903–905 SMBG has been demonstrated to be helpful or to correlate
glycemia (for example, driving or operating hazardous machinery).
with effective management in both insulin-treated and noninsulin-treated
2. RT-CGM alone is not recommended for glucose management in the
diabetes.900,904,906–910 Many different models of glucose meters are avail-
intensive care unit or operating room until further studies provide suffi-
able to suit the needs of the patients and differ in terms of their accuracy,
cient evidence for its accuracy and safety916.
amount of blood needed for each test, ease of use, pain associated with
3. CGM is widely used to evaluate the effectiveness of different thera-
using it, testing speed, overall size, memory functions to store the test
peutic approaches in the management of T2D and also to compare the
results, the likelihood of interferences, the ability to transfer data, procure-
effectiveness of the different oral hypoglycemic agents 917
ment costs of the meter and accessories, special features such as automatic
4. CGM is widely used to assess other issues related to T2D, as to eval-
timing, error codes, large display screen, etc.911 Regarding the accuracy
uate frequency and severity of the dawn phenomenon in non-insulin-
of the glucose meters, though there are several current standards, the most
treated T2D patients across different age categories917
commonly followed are those of the International Organization for
5. RT-CGM devices is recommended in adult patients with T1DM irre-
Standardization (ISO 15197:2013)912 and the U. S. Food and Drug
spective of any values who can afford and use these devices on a nearly
Administration (USFDA).913–915 Currently connected glucose meters
daily basis.916
provide a patient-friendly visualization of blood glucose trends, time
6. Real-time CGM (rtCGM) A or intermittently scanned CGM (isCGM)
spent in range, time spent in hypoglycemia, cloud storage, ability to email
B should be offered for diabetes management in adults with diabetes on
the digital blood glucose diary to the physician’s office along with storing
multiple daily injections (MDI) or CSII who are capable of using devices
the entire information. These glucose meters also provide options for
safely (either by themselves or with a caregiver). The choice of the device
users to enter data on insulin and other medications, calculate insulin carb
should be made based on patient circumstances, desires, and needs.
ratio, and insulin correction factor etc. thereby providing a comprehensive
7. The intermittent use of CGMSs designed for short-term retrospective
digital solution to a motivated patient. SMBG continues to be the most
analysis may be of benefit in adult patients with diabetes to detect noc-
important tool to pick up hypoglycemia accurately and all patients with
turnal hypoglycemia, the dawn phenomenon and postprandial
hyperglycemia and to assist in the management of hypoglycemic unwell as regular evaluation of technique, results, and the ability of the
awareness and when significant changes are made to their diabetes regi- patient/caregivers to adjust the therapy based on data, including
men (such as instituting new insulin or switching from MDI to pump uploading/sharing (if applicable).
therapy). 4. When used as an adjunct to pre- and postprandial BGM, CGM can help
8. CGMS device has been used to assess the effect of acute psychological to achieve A1C targets in diabetes and pregnancy.
stress in T2D 917 5. Periodic use of rtCGM or isCGM or use of professional CGM can be
helpful for diabetes management in circumstances where continuous use
Continuous subcutaneous insulin infusion of CGM is not appropriate, desired, or available.
Insulin Pump Therapy (IPT) 6. Skin reactions, either due to irritation or allergy, should be assessed and
Insulin pumps are meant for Continuous Subcutaneous Insulin Infusion to addressed to aid in the successful use of devices.
mimic physiological delivery of insulin. Insulin pumps unlike conven-
tional syringes and pens offer a plethora of benefits. Over the last two
decades, insulin pumps have undergone significant technology advance-
ments. The indications and contraindications of insulin pump therapy is
the physicians' discretion and based on published guidelines. Selection of
the subject is an important criterion to ensure not only success but also to
avoid the possible hazards of using this technology.
Sensor Augmented pumps

Sensor augmented pumps wirelessly connect with CGM; the earlier de-
vices were only capable of eliminating hypoglycemia to an extent.
Standalone pumps may be used along with SMBG or CGM and currently
have limited application.
Automated Insulin Delivery Systems

The new automated insulin delivery devices, with the help of an integrat-
ed algorithm, has been successful in reaching a TIR of around 80%
eliminating both hypoglycemia and hyperglycemia by changing the basal
rates every 5 minutes in response to sensor glucose levels. The new
Automated Insulin Delivery (AID) system available in India is even ca- Figure 16: Types of insulin pumps928–930
pable of delivering auto bolus doses if the algorithm decides so.
Every eligible candidate with T1D may be offered the best advanced
delivery device fulfilling the criteria for selection.918,919 Technologies to improve clinical decision support and treatment
compliance
Insulin pumps for type 2 diabetes The overall quality of diabetes care still remains suboptimal due to vari-
For type 2 diabetes and other types of diabetes, there is evidence that ous patient and provider-related factors. An organized, systematic ap-
insulin pumps could be beneficial not only in maintaining TIR targets proach to diabetes self-management and continued support from a trained
but also in managing neuropathy, erectile dysfunction etc.920–922 multidisciplinary diabetes care team are thus highly crucial for achieving
Physicians may follow the recommendations for choosing the right can- optimal outcomes.931,932 Many solutions have been identified or are be-
didates for IPT.923 ing employed to achieve this such as redesigning the organization of the
care process, empowering and educating patients, implementing clinical
Training and Troubleshooting decision support systems such as electronic health record tools, using
Insulin pumps and AID require intense training, troubleshooting and follow diabetes detection or management apps and platforms for patients and
up by the multidisciplinary team for several months after initiation.924 The healthcare professionals, etc.931,933,934
merits and demerits need to be discussed in detail with the patient or care- Clinical decision support systems (CDSS) are applications that can
giver for a shared decision making while choosing this option.925 analyze data and aid healthcare providers to make clinical deci-
sions and improve patient care. Classic CDSSs may include vari-
Do-It-Yourself Closed-Loop Systems (DIY) ous features like alerts, reminders, order sets, drug-dose calcula-
DIY is not approved by any scientific organization or by the US FDA. tors, etc. that automatically remind the doctors of a specific action,
However, there are thousands of patients who have created their own or care summary dashboards that provide performance feedback on
Artificial Pancreas with compatible pumps, CGM devices, and down- quality indicators thereby ensuring patient safety and improved
loadable algorithms. Even ADA suggests all clinicians have a knowledge health outcomes. Both commercially and locally developed
on DIY AP to troubleshoot as and when required and should never dis- CDSSs are effective at improving healthcare process measures
courage patients from using it due to the possible benefits.926,927 across diverse settings.935,936
Telemedicine is a disease management strategy whose basic concept
Recommendations923 matches that of a CDSS. With the aid of telecommunications, telemedi-
1. Standardized, single-page glucose reports from CGM devices with cine facilitates remote delivery of health-related services and clinical in-
visual cues, such as the ambulatory glucose profile (AGP), should be formation.937 Various telemedicine modalities have been proven to be
considered as a standard summary for all CGM devices. effective and safe across various patient populations irrespective of their
2. In addition to being associated with microvascular complications, IR can type of diabetes. They have been also associated with time savings, cost
also be used to assess glycemic control. For evaluating the treatment regi- savings, high appointment adherence rates, and high patient satisfaction.
men, time below target and time above target are also useful parameters. In populations with limited access to care, telemedicine effectively im-
3. It is crucial for diabetics/caregivers to receive initial and ongoing edu- proves the overall disease outcomes.938–942
cation and training, whether they are receiving it in person or remotely, as
Limitations SPECIAL SITUATIONS

Use of diabetes technology depends on availability of technology, cost, Post-Transplant Diabetes (PTDM)
needs, desires and skills of persons living with diabetes and their care-
givers. Lack of proper education, training and follow up can limit the RECOMMENDED CARE
intended benefits of diabetes technology. People using CGM devices will

still need BGM for reasons ranging from calibration to rapidly changing
glucose levels. Wide adoption of CSII and RT-CGM is limited by cost,
psychosocial, and educational factors943. Pre-transplant assessment: History of diabetes, family history of diabetes, symptoms of
microvascular and macrovascular complications, physical assessment including BMI,
Contact dermatitis/Allergy has been reported with CGM/Pump. HBA1c, blood glucose monitoring as a part of pre-operative evaluation
Digital health technology (Internet, monitoring, coaching, connec- Perioperative hyperglycemia management as per in-hospital hyperglycemia protocol with
tion, lifestyle apps) only from reliable and verified resources backed insulin
Treatment regimen upon discharge to be individualized based on the degree of
by clinical evidence and real-world performance/outcomes should be hyperglycemia, comorbidities, and other factors
used. Limitations may range from inadequate evidence on app accu- For patients with hyperglycemia in the immediate post-operative period, regular monitoring
racy, clinical validity, lack of training provision, poor interoperabil- of blood glucose on follow-up
ity, standardization, and insufficient data security944. Lack of insur- Individuals with pre-operative IGT or hyperglycemia in the perioperative period are at greater
risk of PTDM and need close follow up
ance coverage on advanced digital technologies and devices may also Screening for risk factors of PTDM – modifiable, non-modifiable
restrict their use in India945. Assessment for PTDM to be done not earlier than six weeks after transplantation as per ADA
criteria for DM (FBS, OGTT, HBA1c)
For patients diagnosed to have PTDM, dietary advice and individualization of therapy –
Future of Technology in Diabetes OADs or insulin
The use of technology in the management of PwD is increasing at Patients with PTDM are at greater risk for infections, transplant rejection, cardiovascular
a rapid pace due to proven benefits. Several new frontiers are disease
being explored and a number of new technology-based products
are in the pipeline.
Digital Therapeutics – These are the products that deliver evi-
dence based therapeutic interventions to patients that are driven
by high quality software programs to prevent, manage or treat a
medical disorder or disease. These products have been shown to
improve patient compliance, therapeutic success and economic
outcomes in the management of PwD946.
Self-care & Wellness apps – Several mobile applications that help the LIMITED CARE
patients in monitoring their vitals, calorie intake, activity etc. are currently
Preoperative screening for diabetes/ IGT
available. These are useful for calorie counting, carb counting, calculating
Perioperative blood glucose monitoring
insulin doses, tracking daily activity, tracking the glycemic profile.
Reassessment at six weeks for PTDM
Utmost care should be taken while recommending any such apps to the
Individualized treatment
patients with regards to its accuracy and data security.
Non-Invasive Glucose Monitors – Various non-invasive glucose moni-
toring devices have already been introduced in the market and many more Background
are currently being developed. There is no sufficient evidence to recom- Post-transplant diabetes mellitus (PTDM) is the development of diabetes
mend any of these at present mellitus after solid organ transplantation. NODAT- New Onset Diabetes
After Transplant, a frequently used terminology, may be misleading as
Role of Physicians individuals may have pre-existing IGT/DM, which gets discovered dur-
- The physician should make themselves aware and adept at using tech- ing the post-transplant period. PTDM is seen in 10-40% of transplants
nologies in diabetes with newer technologies and newer versions being and has been known to increase the risk of infection and mortality rates.
constantly updated, the physician should guide the patient towards ap- Timely evaluation and management of PTDM reduce morbidity, mortal-
propriate technology and digital solution selection. ity, and transplant rejection rates.
- The physician should also be involved in training the patient in correct
use of the tool/device, interpretation of reports through ongoing educa- Definition And Diagnosis Of New-Onset Diabetes After Transplantation
tion and training. In 2003 the International Expert panel consisting of experts from fields of
- The physician should also make the patient aware of the limitations of transplant medicine and diabetes suggested that the definition and diagnosis
technology and train to use conventional methods where needed. of diabetes and impaired glucose tolerance should be based on the defini-
tion and diagnosis described by the World Health Organization.948 In 2011,
Implementations the American Diabetes Association (ADA) incorporated hemoglobin A1C
Almost ninety percent of the world’s population is estimated to be within (A1C) > 6.5% as a diagnostic criterion for diabetes mellitus in the general
the reach of a mobile network947 and the number of smartphone users also population based on the observed association between A1C level and the
seems to be on the rise. Therefore, the feasibility of mobile apps to em- risk for future development of retinopathy.949 In 2014, the International
power patients and healthcare providers is now a step higher than other Expert Panel recommended expanding screening tests for PTDM using
approaches. Numerous mobile apps for diabetes management are nowa- postprandial glucose monitoring and A1C. However, because of potential
days available to help clinicians and/or the patients themselves to track confounding factors, the A1C test is not recommended early after trans-
and manage diet, physical activity, blood glucose targets, and medications plantation (arbitrarily defined as within 45 days after transplantation).950 A
Diabetes technologies are meant for saving time and better short-term and normal A1C does not exclude the diagnosis of PTDM in the presence of
long-term outcomes. The choice should depend on the knowledge, infra- early post-transplant anaemia and/or dynamic kidney allograft function.
structure, and the need. The risk factors of PTDM are mentioned in Table 1.
Table 28. Risk factors for PTDM attractive anti-hyperglycemic agent to reduce the likelihood of PTDM
in high-risk individuals960 benefits of metformin need to be weighed
Non-modifiable Potentially modifiable Modifiable against the risks associated with metformin in the context of impaired
African American, HCV Individualization of
Hispanic CMV Immunosuppressive renal function (e.g., lactic acidosis). However, this association has been
Age > 40–45 years Pre-transplant IFG/IGT therapy the subject of critical analysis961 and well-designed clinical trials are
Recipient male gender Proteinuria • Tacrolimus necessary to shed light on metformin’s benefit versus risk ratio. Dose
Family history of DM Hypomagnesemia • Cyclosporin
adjustments or cessation of oral anti-diabetic agents in renal allograft
HLA A30, B27, B42 • Corticosteroid
HLA mismatches • mTOR inhibitors dysfunction should be individualized.
Acute rejection history • Anti CD25 mAB
Obesity or another
Deceased donor Modification Of Immunosuppression
component of the
Male donor Due to the lack of well-defined guidelines, modification of immunosup-
metabolic syndrome
Polycystic kidneys
pression to alleviate the incidence of PTDM should be tailored to each
patient. Reduction in immunosuppression should be weighed against the
Pathophysiology risk of acute rejection. The beneficial effect of steroid avoidance or with-
The pathophysiology of PTDM involves increased insulin resistance and drawal on the incidence of PTDM has been questioned by experts in the
decreased insulin secretion. An immunosuppression regimen is one of the field because rapid steroid taper and the use of lower target cyclosporine
leading causes of PTDM, affecting insulin secretion and action.951 and tacrolimus levels are now standard practice.950
In a meta-analysis of controlled clinical trials to assess the safety and
Detection Of PTDM efficacy of early steroid withdrawal or avoidance, Pascual et al. showed
Pretransplant that steroid avoidance or steroid withdrawal after a few days reduced
In 2004 International Consensus Guidelines suggested that a PTDM incidence among cyclosporine but not tacrolimus-treated kidney
pretransplant baseline evaluation should include a complete medical transplant recipients.962 However, among cyclosporine-treated patients,
and family history, including documentation of glucose history.952 acute rejection episodes were more frequently observed in steroid avoid-
Those with risk factors for metabolic syndrome can be screened further ance compared with conventional steroid-treated groups.963 The use of
with laboratory testing. tacrolimus and mTOR inhibitor combination therapy may increase
PTDM risk and should probably be avoided. Nonetheless, a low dose
After Transplant calcineurin inhibitor (cyclosporine or tacrolimus) and mTOR inhibitor
The expert panel suggested that patients with early post-transplant hyper- combination therapy seem justifiable in transplant recipients with a his-
glycemia (defined as hyperglycemia 45 days after transplantation) should tory of malignancies (such as skin cancers, renal cell carcinoma, or
not be diagnosed as PTDM. New onset perioperative hyperglycemia is Kaposi sarcoma).
common and may be partly due to immunosuppressive therapy and stress
hyperglycemia.953 Deterrence And Patient Education
Pre-transplant patients should receive counseling regarding the risk fac-
Strategies For Prevention And Treatment Beyond Modification Of tors of developing PTDM and how to prevent it. Attention to avoid
Immunosuppressive Regimens weight gain is an established step to prevent PTDM. Weight loss can
prevent PTDM in overweight patients with prediabetic status. In high-
Prevention risk groups such as obese patients, the goal should include weight loss
Pre-operative dietary and lifestyle modification is ideal for all potential with diet, increasing physical activity with a target weight loss of 5% to
transplant recipients regarding their risk of developing PTDM and may 10% of total body weight, and following up with the dietitian before and
reduce the risk of patients with prediabetes developing PTDM. Sharif after transplant. Patients should be advised to eat a healthy, low-calorie,
et al.954 demonstrated the potential for benefit from lifestyle modification low-fat diet. Weight loss immediately after transplant is not recommend-
in kidney allograft recipients with impaired glucose tolerance. ed, as it will delay wound healing.
After being diagnosed with PTDM, as with DM, self-glucose monitoring
Pharmacotherapy and compliance with treatment are essential. Also, patients should be
Insulin: is the only safe and effective agent in the context of high gluco- aware of the importance of an annual eye exam, which is even more
corticoid doses and acute illness early post-transplant. Still, the early and important than in traditional diabetes patients. PTDM patients are prone
aggressive use of insulin may also have long-term benefits. In a random- to the acceleration of cataracts due to the universal use of corticosteroids
ized controlled trial, Hecking et al.955 demonstrated the benefit of early and immunosuppressants. Foot exams should be part of every clinical
basal insulin therapy following the detection of early posttransplant hy- visit. Immunosuppressants place PTDM patients at increased risk of in-
perglycemia (<3 weeks) at reducing subsequent odds of developing fections, so compliance with annual influenza and pneumococcal
PTDM within the first-year post-transplantation by 73%. Although a vaccines is critical in this population. Those patients who desire to get
relatively high glucose threshold of 200 mg/dL (evening or fasting) has pregnant should be encouraged to wait at least one year after the trans-
been previously suggested, it may be reasonable to lower this threshold, plantation to decrease the risk of rejection. The transplant team should be
but further research is warranted before firm guidance can be issued. The involved in all stages before, during, and after pregnancy to reduce the
armamentarium of anti-diabetic therapy is increasing, and individual comorbidities of both mother and baby.964,965
pharmacological risk/benefit profiles must be evaluated in the context
of transplantation.956–958 Further work to understand the pathophysiology Prognosis
underlying PTDM development and progression should assist the choice PTDM decreases patient survival by increasing both cardiovascular events
of pharmacological agents and form the basis of targeted clinical trials. and the risk of infections. PTDM is associated with a higher prevalence of
OADs: Werzowa et al.959 in a randomized controlled trial, compared the rejection and post-transplant renal failure. Studies showed that graft sur-
safety and efficacy of vildagliptin (dipeptidyl peptidase-4 inhibitor) with vival in patients with PTDM was 48% and 70% in patients without PTDM.
pioglitazone (a thiazolidinedione) or placebo in kidney allograft recipi- Also, studies demonstrate that in kidney transplant recipients, cardiovas-
ents with impaired glucose tolerance. Adverse events were equivalent in cular events are 2 to 3-fold more in PTDM in comparison with other
all three arms, and pioglitazone and vildagliptin produced a comparable patients. Additionally, diabetic microvascular complications develop more
reduction in 2-h postprandial glucose levels. Metformin may be an rapidly in patients with PTDM than in traditional DM.965–967
Conclusion
PTDM is a common complication after solid organ transplantation and
has been reported to be associated with increased morbidity and mortality.
Risk stratification, intervention to minimize risk, and early diagnosis may
alleviate the incidence of PTDM and improve outcomes following solid
organ transplantation. Currently, early initiation of basal insulin therapy
in patients with new onset hyperglycemia during the first post-
transplantation week to preserve β-cell function and progression to overt
PTDM cannot be routinely recommended. Management of established
late PTDM should follow the conventional approach and guidelines es-
tablished for the general population. Medical intervention is often neces-
sary when lifestyle modification fails to achieve glycemic control. The
choice of one antihyperglycemic agent over the other should be based on Background
individual agents' potential advantages and disadvantages. Metformin The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
appears safe in kidney transplant recipients with mild to moderate renal pandemic has presented unprecedented challenges and tremendous strain
impairment (eGFR 30-60 mL/min). SGLT2 inhibitor has been suggested on healthcare authorities. As of 3rd August 2022, there have been 575
to be suitable for use following heart transplantation. Its use after kidney million confirmed cases and 6.3 million deaths worldwide, with India
transplantation should be individualized. Similar to the general popula- reporting the second highest number of confirmed cases worldwide at
tion, insulin therapy should be considered in individuals with suboptimal 44 million and 0.5 million deaths.968 Diabetes is one of the most common
glycemic control despite multiple antihyperglycemic agent combination comorbidities in Covid19, with an estimated prevalence of 7-58%. The
therapy. variable prevalence has been attributed to the age and gender proportions
of the included patients in various studies, hospitalization status, and
DIABETES AND COVID-19 severity of illness, with higher prevalence noted in individuals with severe
Recommendations disease.969,970 A bidirectional relationship between diabetes and Covid19
infection has become apparent since the beginning of the pandemic. Data
from clinical studies have uniformly confirmed the poorer Covid19 out-
Recommended care
comes in diabetic individuals, including increased risk of hospitalization,
the severity of illness, intubation and ICU admission rates, and mortali-
ty.971 The ambient hyperglycemia is postulated to increase viral replica-
tion in-vivo directly. Additionally, acute hyperglycemia can upregulate
ACE-2 expression, increasing viral entry. Chronic hyperglycemia, on the
other hand, decreases ACE-2 expression, shifting the balance towards a
pro-inflammatory milieu. Diabetes is also characterized by compromised
innate immunity and chronic low-grade underlying inflammation, which
is heightened with an exaggerated release of pro-inflammatory cytokines
like IL-6, potentially mediating the severity of Covid19 infection in dia-
betic individuals. Other non-hyperglycemia-related factors for adverse
clinical outcomes include underlying comorbidities like hypertension,
obesity, cardiovascular disease, and chronic kidney disease
(CKD).972,973 Conversely, Covid19 also has a deleterious effect on gly-
cemic status. Exocrine pancreas and islet cells express ACE-2 receptors,
which can mediate viral entry and direct pancreatic damage. This can
clinically translate into exocrine pancreatic injury, including pancreatitis,
in addition to worsening pre-existing hyperglycemia and new-onset hy-
perglycemia. Additionally, indirect mechanisms like overactivation of the
renin-angiotensin-aldosterone (RAAS) system, corticosteroids, and cyto-
kine release can contribute to impaired glycemic status. IL-6 is the pri-
mary cytokine culprit and can drive ketogenesis resulting in an increased
risk of diabetic ketoacidosis.974,975 Hence, the guidelines aim to highlight
the importance of early detection of hyperglycemia and its attendant risks
and propose treatment and follow-up algorithms to aid the management
of diabetes in Covid19 patients. The guidelines also cover the manage-
ment of hyperglycemia in these patients, which may be part of previously
undiagnosed diabetes or transient hyperglycemia related to stress and
other factors, including glucocorticoids.
Considerations
Timely diagnosis of hyperglycemia in Covid19 patients with or without
diabetes and appropriate monitoring and management during hospital
stay has important implications for morbidity and mortality. Guideline-
recommended protocols can simplify the management of hyperglycemia
for treating physicians both in-patient or in the outpatient setting.
Monitoring For Dysglycemia After The Acute Illness existing DM” if known as diabetic or on anti-diabetic agents. Other patients
Rationale and evidence with hyperglycemia can be categorized as “undiagnosed DM” if HbA1c
≥6.5% and “stress-induced hyperglycemia” if HbA1c <6.5%.
Primary prevention of infection in diabetic individuals Continued monitoring for hyperglycemia during the hospital stay
• Hyperglycemia after admission and hypoglycemia have been demonstrated
• Glycemic control and management of comorbidities should be optimized if to be associated with poorer outcomes in Covid19.986 Hence, we recom-
not already appropriate with the ongoing medications.972 The medications mend that continued monitoring for hyperglycemia should be done daily in
can be adjusted at the treating physician’s discretion, with the primary target patients with hyperglycemia at presentation, in concordance with the
of optimizing overall glycemia as per targets recommended by general MOHFW guidelines.979 This would include patients with
guidelines for diabetes. Previously held concerns about the role of ACE ◦ Fasting plasma glucose ≥110 mg/dl and/or HbA1c ≥6.5%
inhibitors and angiotensin receptor blockers (ARBs) in mediating adverse ◦ Pre-meal capillary BG ≥140 mg/dl
outcomes in COVID-19-infected patients have been largely mitigated. ◦ Post-meal/ Random capillary BG ≥180 mg/dl
These medications can be safely continued as per clinical indications.975 • Additionally, hyperglycemia can develop during the course of Covid19
• Telemedicine has flourished during the pandemic and has been a bless- illness, especially with clinical deterioration and corticosteroids. Hence,
ing in disguise. Most diabetic patients with Covid19 can benefit from we recommend continued monitoring of blood glucose daily in these
remote consultations, and all attempts should be made to adopt telemed- admitted patients as well.
icine practices in outpatient care. • Glycemic monitoring should be performed with a reliable glucometer,
• Outpatient visits and consultations must be used to emphasize updated the frequency depending upon the treatment chosen for hyperglycemia
vaccination status, including booster/precaution doses as per the nation- management. Capillary blood glucose values should be interpreted cau-
al guidelines. tiously in sick patients with hypoxia and hypoperfusion.
• Continuous glucose monitoring (CGM) real-time devices may be used as an
Screening for hyperglycemia at presentation alternative to glucometers to limit contact exposure to healthcare profes-
• Plasma glucose at the time of hospitalization has been consistently sionals. This would provide glucose values for timely adjustment of medi-
demonstrated to be an independent predictor of adverse clinical out- cations, including insulin, alert for extremes of blood glucose values, and
comes. A recent meta-analysis confirmed blood glucose at admission minimize close contact between health care providers and the patient during
as a significant predictor of mortality in diabetic patients with COVID- capillary glucose monitoring. CGM devices which require autocalibration /
19, in addition to older age, male gender, insulin use, and presence of no calibration with capillary BG values may be preferable in this scenario.
comorbidities like cardiovascular disease, CKD, and chronic obstruc- CGM has demonstrated reliability and utility in critically ill Covid19 patients
tive pulmonary disease (COPD).976 This was confirmed in a study by on intravenous insulin infusion in a few studies.987,988 However, CGM
Kumar et al., where higher plasma glucose at admission strongly cor- devices are not widely available owing to cost concerns, with many medical
related with inflammatory markers, was predictive of moderate-to- professionals not well-versed with the meaningful interpretation of CGM
severe disease, and patients with plasma glucose of 180 mg/dL or less data. It is recommended that physicians get familiar with newer technologies
had better survival.977 In another recent meta-analysis, admission like CGM and get adequately trained to manage diabetic patients using
fasting blood glucose was found to be an independent predictor of CGM-derived metrics and graphs. Limitations of CGM include a small-
disease severity, with every one mmol/L increase in fasting blood glu- time lag between blood glucose and interstitial glucose, limited utility in
cose translating into a 33% increased risk of disease severity.978 the presence of hypoxemia, hypoperfusion, and rapidly fluctuating values,
• Clinical guidance protocols have been previously published by Gupta and a wider coefficient of variation at extremes of blood glucose values. We
et al. and the Ministry of Health and Family Welfare (MOHFW) for the recommend the following CGM-based glycaemic targets: -
management of diabetes in Covid19 infected patients.979,980 We recom- ◦ Time-in-range, TIR (70-180 mg/dl): >70% (>50% in elderly individuals)
mend that random glucose be obtained immediately at presentation in ◦ Time-below-range, TBR (<70 mg/dl): <4% (<1% in elderly individuals)
Covid19 infected patients, followed by documentation of pre-meal and • Inpatient glycemic control is vital for better long-term outcomes in Covid19
post-meal glucose values after the first major meal post-admission. infected patients. In a study from China, T2DM patients with well-
Venous samples for fasting plasma glucose can also be sent if laboratory controlled blood glucose between 70-180 mg/dl during the hospital stay
facilities are available. This will aid in the early identification of hyper- had markedly lower mortality.989 This was similar to the results observed in
glycemia, timely management, and prognostication. the study from India by Kumar et al., where higher mortality was seen in
• Increased plasma glucose at admission can result from pre-existing Covid19 patients with BG >180 mg/dl on admission.977 Similarly, inpatient
uncontrolled diabetes mellitus, newly detected undiagnosed diabetes BG values of >180 mg/dl were associated with a longer median length of
mellitus, the direct effect of the virus on pancreatic β cells, or stress/ stay and higher mortality in the study by Bode et al. 990
drug-induced hyperglycemia. New-onset hyperglycemia was noted in • We agree with the MOHFW guidelines (12) concerning capillary BG
as many as 10.3% of patients without known pre-existing diabetes at targets and recommend the following glycemic targets
admission in the study by Kumar et al.977 ◦ Patients on basal-bolus regimen: Premeal BG < 140 mg/dl, post-meal
• The PISA COVID-19 study revealed that patients with new-onset hy- BG <180 mg/dl
perglycemia had the highest mortality, twice that of normoglycemic ◦ Patients on intravenous insulin infusion: Target range of 140-180 mg/dl
patients, and 30% higher than patients with pre-existing diabetes
mellitus.981 Similar findings of worse outcomes in new-onset hypergly- Implementation
cemia compared to pre-existing DM have been demonstrated in other Standard protocols, as recommended here and in other society guidelines
studies.982–984 This might be secondary to occult end-organ damage in must be widely disseminated among practicing physicians for quality
undiagnosed diabetic individuals or insulin secretory defects and in- care. We would like to re-emphasize the importance of screening for
creased insulin resistance resulting from a severe infection leading to hyperglycemia at initial presentation and the continuation of glucose
pancreatic β-cell destruction, a more severe inflammatory state, and monitoring in high-risk individuals. The choice of therapy should be
corticosteroid use. Conversely, it can be argued that known diabetic based on the patient’s clinical condition, comorbidities, any contraindica-
individuals tend to have better control of hyperglycemia and comorbid- tions to specific medications, and severity of hyperglycemia. The goal is
ities. This is supported by the fact that diabetics with optimal glycemic to achieve the recommended glycemic targets for better clinical out-
control have better outcomes than patients with poor control.985 comes. All normoglycemic discharged patients should be followed up
• Venous samples for HbA1c should be sent on admission at centers where for new-onset hyperglycemia. If normoglycemic, further screening
such laboratory facilities are available. Patients can be categorized as “pre- should be based on the prevalent screening recommendations.
Background
Travelling is defined as an individual’s exposure to unfamiliar socio-
environmental places, irrespective of the purpose. Those with chronic
illnesses, like diabetes, may be vulnerable to the emotional and physical
stresses associated with traveling. However, when unfamiliar foods, un-
accustomed climate, different time zones, and social conditions are con-
sidered during times of travel, patients may face challenges in managing
their diabetes .991 A study conducted in Aberdeen, UK, showed that 15%
of insulin users stated that their use of insulin affected their choice of
travel destination, both in terms of health risk in developing countries
and avoidance of long-haul travel.992 However, individuals with diabetes
can travel safely with adequate preparation and appropriate self-
management skills.
Pre-Travel Recommendation
Visit treating Health Care Professionals (HCP)
Figure 17: Approach to management of hyperglycemia in patient
Patients with diabetes planning to travel should schedule an appointment
with Covid19
with their treating physician at least a month in advance of their trip to
allow for planning of diabetes care when traveling. This will also enable
an updated assessment of glycemic control, evaluation and review of
Travel and Diabetes
travel risks, and a discussion of the patient to minimize these risks. In
Recommendations
addition, the physician can remind the patient and reiterate some impor-
tant self-management principles, e.g., recognition and treatment of hypo-
glycemia symptoms, sick day guidelines, and self-monitoring of blood
glucose requirements. It is important to procure a prescription/letter from
the physician describing the patient’s medical condition, their current
diabetes medication regimen, and the patient’s medical necessity to carry
sharps, e.g., needles and lancets, if the patient is on an insulin re-
gime.993,994 It is prudent to advise the patients to plan for travel delays
and lost luggage, so taking twice as many diabetes supplies and medica-
tions is recommended, preferably dis tributed in different luggage bags.
Those planning to travel should schedule an appointment with their

treating physician, at least a month in advance of their trip for an
updated assessment of glycemic control and should also procure a
prescription describing the patient’s medical condition, and
medication. A diabetic individual should also carry an extra number of
medicines that are distributed properly.
Know your destination

It is of utmost importance to find information regarding the climate and
environmental conditions of the destination. Extremes of weather can
adversely affect the health of the patient and/or degrade medications,
supplies, and equipment 995,996. Patients with diabetes are more suscep-
tible to environmental stressors than their counterparts. Patients taking
insulin or other injectable medications that are temperature sensitive
should investigate the availability of refrigeration, e.g., refrigerators in
hotel rooms and travel cold packs, at their destination and plan if such
facilities do not exist, i.e., travel cold packs can be packed prior to depar-
ture. Suitable clothing should be carried based on the climate at the des-
tination. Protective gear such as hats/sunglasses/sunscreen, gloves/mit-
tens/boots, and comfortable footwear will enable patients with diabetes
to enjoy their trip without putting themselves at higher risk for heat ex-
haustion, cold exposure, or foot ulcers.997
Information regarding the climate and environmental conditions of the

destination is a must. Extremes of weather can adversely affect the
health of the patient and/or degrade medications, supplies, and
equipment. Patients with diabetes are more susceptible to environ-
mental stressors than their counterparts, such as increased incidence
of heat exhaustion, cold exposure, or foot ulcers.
Diet
Food options for patients with diabetes may be limited during travel,
especially if one is traveling out of the country, so planning is important.
This is more relevant during air travel, as travel by road/train and mari- What To Pack
time travel offer greater flexibility in dietary choices.998 For flights during Physician prescription
which a meal will be served, there is an option of selecting your choice of 1. Letter should be in English.
meal well in advance. The destination and flight duration are also impor- 2. Whether the patient has type 1 or 2 diabetes.
tant with regard to the food options available. Packing healthy snacks in 3. Medications (generic name) and dosages—if on insulin pump, settings
carry-on luggage can take care of disrupted dietary patterns during the and basal-bolus backup regimen, in case of pump malfunction, should be
flight. Access to such foods may be limited during travel, and it is rec- included.
ommended to be carried to help prevent or treat hypoglycemic events. 4. Rescue medications, viz glucose gel, tablets, and a gluca gon pen.
When traveling to countries where English is not the primary language, 5. Supplies with quantities mentioned (glucometer, testing strips, lancets,
food labels and restaurant menus may be difficult to interpret. In such syringes/pens, and batteries).
situations, investigating specific dietary options before departure via the 6. Necessity to carry sharps (needles and lancets).
internet, may be helpful. When unsure, it is best to rely on known low- 7. Physician name and contact details.
carbohydrate options, e.g., salads, nuts, and eggs.999
Food options for diabetics may be limited during travel and travel Always keep double medicines and supplies than needed for travel. Do
planning should offer greater flexibility in dietary choices; packing not pack them all in one place. Keep half the supplies in a bag that will
healthy snacks in carry-on luggage can take care of disrupted dietary be with the concerned individual in person, irrespective of the mode of
patterns. travel.
Medication • Health insurance policy/card or details

For insulin users, it is important to note that insulin concentration varies in • Diabetes medications and prescriptions for them
various countries. Available options include U-40, U-100, or U-200. The • Rescue medications (glucose gel, tablets, and glucagon pen)
use of the correct syringes with specific insulin con centrations is essen- • Supplies (syringes, lancets, test strips, sharps container)
tial, since using wrong syringes may deliver incorrect dose of insulin. • Two glucose meters (in case one fails) with extra batteries
This concern is dimin ished in those who use insulin pens rather than vial • If on insulin pump, twice as many pump supplies as may be needed
and syringes. It is also important to note that the unit of blood glucose • Coolant/cold packs/insulin wallets for insulin users
measurement in India is mg/dL, but many other countries use mmol/L. • First aid kit
This will be important if someone’s glucose meter malfunctions while • Comfortable shoes
abroad and another one needs to be bought locally. Travelers should be • Protective clothing, depending on destination climate
also aware that not all insulins, other injectables, or oral diabetes medi- • Some snacks to avoid hypoglycemia
cations available in India will be available in every country throughout
the world and that different names may refer to medications.1000
Therefore, it is important to carry a list of all medications with generic One must carry physician’s prescription, health insurance policy,
name and their dosages. Those who are on insulin pump therapy should medications and prescriptions for them, rescue medications, snacks,
contact the manufacturing company for contact details at the destination, supplies, glucometers, coolants, pumps in double, a first aid kit,
should there be a need. They must discuss with their treating physician comfortable shoes, and protective clothing.
about an alternative basal-bolus insulin regimen in the event of pump
failure. Immunization against common and travel-related vaccine-pre- Air Travel
ventable diseases is recommended, as per individual country recommen- Airport security
dations, prior to departure. Travel security, both national and international, has become strict in re-
cent years. When traveling by air, outside the country, passengers should
contact the airline to find out if the destination country has any specific
It is advisable to disconnect the pump during take- off or landing as
airport security restrictions or requirements regarding diabetes medica-
change in cabin pressure may lead to excess insulin delivery. Insulin
tions or equipment. If a traveller is on an insulin pump or a continuous
concentration varies in various countries; hence, using the correct
glucose monitor (CGM), it is important to ensure that the device not be
syringes is essential. Unit of blood glucose measurement may also be
removed since it is attached via a catheter underneath the skin. It is also
different. Availability of medications may also be an issue. So, it is
prudent to check with the pump CGM manufacturing companies regard-
important to carry a list of all medications with generic name and their
ing recommendations for radiation exposure. Several companies allow
dosages. Immunization against common and travel-related vaccine--
the pas sage of their equipment through metal detectors but do not rec-
preventable diseases is recommended. Those on insulin pump therapy
ommend that their products be run through the x-ray machines or body
should get in touch with the manufacturing company and it is advis-
scanners that implement x-ray technology, due to the potential risk of
able to disconnect the pump during take off or landing as change in
radiation-induced malfunction. This information may be available online
cabin pressure may lead to excess insulin delivery.
and can be printed and shown to security personnel.
Travel health insurance
Where feasible, travellers need to get in touch with their medical insur- Airport security requiring patients on pump or CGM to go through
ance companies and review their medical coverage policies during travel scanners should be warned from doing so as it may cause
should unforeseen emergencies arise. One should have easy access to radiation-induced malfunction. These devices should not be removed
their health insurance identification card. It is also important to locate also.
the nearest hospital and phar macy at the destination, before arrival, in
case medical assistance is required. It would be wise to ensure that health Storing diabetes medications and supplies
insurance is accepted at these facilities beforehand to avoid expensive Carrying snacks that contain carbohydrates is a good backup in addition to
medical bills or unforeseen costs. glucose tabs, gels, or glucagon kits, in case blood sugars fall low. Having
diabetes supplies in carry-on luggage is also beneficial. Temperature extremes
Individuals with diabetes should also carry travel health insurance. occur more frequently in the lug gage compartments than in the cabin areas
on airplanes, which is important to consider when carrying insulin vials or
pens. Injectable diabetes medications have optimal storage temperatures be- to stand and walk during long flights every 1–2 h while awake and
tween 2 and 8 °C while oral medications can be stored between 20 and 30 perform seated dorsiflexion/plantarflexion exercises to avoid venous sta-
°C.1001 Insulin pumps have temperature tolerances of 5–40 °C and CGM sis that could potentiate clot formation. Staying well hydrated throughout
devices from 10 to 40 °C; but specific temperature ranges vary by manufac- the flight may also decrease the risk of DVT formation.
turer. Blood glucose testing strips should be kept in tightly sealed containers
to avoid exposure to moisture. Do not expose them to extreme temperatures.
Those with diabetes are at an increased risk of developing deep venous
Travelers should read the package inserts of their medi cations, devices, and
thrombosis, so they should be encouraged to stand and walk during
equipment to ensure proper functioning. In India, very recent Clinicare (India)
long flights every 1–2 h and perform seated dorsiflexion/plantarflexion
Pvt. Ltd., a Mumbai-based company, has launched the FRIO ® Insulin
exercises to avoid venous stasis; also, one must remain well hydrated.
Wallet. This is meant for keeping insulin cool while traveling and is a good
option when one has no access to refrigeration or during power shortages
while traveling. Unlike traditional insulin-carrying cases, FRIO®’s cooling Train travel/road travel
properties are not derived from an ice pack or anything that needs refrigera- In general, traveling by train and/or road is a much more flexible option
tion. It is easily activated by water. It is an environment-friendly green reus- for a person with diabetes, especially concerning diet and medications.
able product and is convenient to be carried around on oneself or in one’s However, it is mandatory to have a visit with the HCP pretravel, and it is
hand baggage.1002 most definitely beneficial to know details about the destination. Since
train/road travel is feasible only within the country, specific travel health
insurance is not a pre-requisite. Still, it would be helpful to review one’s
Air travel requires patients to carry carbohydrate snacks, insulin, insulin medical coverage policies and get a list of hospitals/clinics wherein their
pump, and medications in carry-on baggages to maintain temperature current insurance will be accepted, at the destination, should unforeseen
stability. emergencies arise. The list of what to pack remains the same, as above.
For carrying and storage of insulin, as mentioned above, FRIO® Insulin
Insulin on board Wallet may be a good option.1002
Depending on the duration of the flight, insulin may need to be administered
on board an airplane. Due to pressure differences in the cabin area, resistance
may arise when using syringe plungers to draw insulin.1003 Similarly, with Train travel is much more flexible; though health insurance is not
required, one must pack the same essentials in carry-on bags.
insulin pen devices, there may be a leak in insulin when applying the pen tip
needle for use. Recent data suggests the possibility of unintended insulin
delivery during ascent from bubbles precipitating out of insulin solution in Recommendations After Arriving At The Travel Destination
the microtubules according to pressure gradients for those using insulin pump Physical activity
therapy on board an aircraft.1004 In addition, there have been reports of sig- Depending on travel itineraries, there may be an inadvertent increase in
nificant unintended insulin administration due to plunger movements during walking more than one is accustomed to (whether at their destinations or
rapid cabin depressurization during an emergency. More data is needed before in airports between security and boarding gates). This increase in physical
recommendations regarding insulin pump management during flight can be exercise may increase glucose utilization and lower blood sugars in ad-
made.1005 Travelers must check their blood sugars frequently due to the effects dition to more rapid insulin absorption. In such a situation, it may be
that stress, altered eating habits, and altered medication administration times useful to slightly decrease the insulin dosages or eat more carbohydrates
may have on overall blood glucose control. and snack between meals to keep blood glucose levels controlled appro-
priately.1010 It is also advisable to check blood sugar levels more frequent-
ly, to be able to keep a track on overall glycemic control. This is consid-
Due to pressure differences in the cabin area, there might be some ering exposure to a new cuisine, a new environment, and a potentially
irregularities in insulin administration. Even in insulin pumps, similar different physical activity levels.1003 With increased walking comes the
issues may arise due to bubbles precipitating out of insulin solution in need for comfortable footwear since blisters and abrasions can develop
the microtubules. Blood sugars must be frequently checked. from improperly fitted shoes. Wearing sandals on beaches to reduce the
introduction of bacteria and other stray ob jects is advisable.1011
Traveling across time zones
Diabetes management is based on a 24-h cycle. When traveling from west
During travel, there will be an inadvertent increase in walking, for
to east, one should remember that the day shortens compared with when
which insulin requirement will decrease; frequent snacking may
traveling from east to west, when the days become longer .1006 Usually, if
also help. Blood sugar must be measured more frequently.
fewer than five time zones are crossed dur ing travel, adjustments to
insulin dosing are generally not necessary.1007 If more than five time
One must wear proper footwear to avoid ulcers and infections.
zones are crossed, the treating physician should make specific recommen-
dations to discuss how insulin dosing or timing of administration should
change based on time zone differences. For those on oral medications, Keeping hydrated
timing is less important. Patients should be educated not to take their It is important to remain hydrated, especially when traveling to hotter
sulfonylurea if they will be missing meals during travel to avoid hypogly climates. It is also important to know the quality of the potable water
cemia. However, other oral agents may be continued. Generally, it is available at one’s destina tion to avoid traveler’s diarrhea and the ensuing
helpful if travelers keep their wristwatch set to their departure time zone, dehydra tion.1012,1013
at least for the first day of travel..
Conclusion
Travelers with diabetes can face challenges during their trips, particularly
Traveling across less than five time zones does not require insulin dose international travelers. In general, traveling within the country in the same
adjustments, but in greater than five time zones, dose and timings need time zone, be it by air or train, poses less of a challenge than traveling
to be adjusted. outside the country to a destination with a different time zone. Being
prepared by planning, in advance, will be helpful to achieve management
Prevention of venous thromboembolism in air travellers of diabetes and boost self-confidence. This is of utmost importance to
Those with diabetes may be at an increased risk of developing deep achieve appropriate patient glucose control amidst changing diet, time
venous thrombosis (DVT).1008,1009 Therefore, they should be encouraged zone difference, and a new environment. Patients should meet their
treating physician at least 1 month prior to travel, to allow time for the • Furthermore, if the patient is receiving intravenous insulin, blood glu-
physician to generate a travel letter and/or prescriptions for needed med- cose monitoring should be more frequent, ranging from 30 minutes to
ications, equipment, and supplies. Diabetes is manageable when patients every 2 hours.
and their providers work together to formulate a treatment plan for travel.
No destinations should seem “off-limits” to individuals with diabetes, Therapeutic goals
given the available resources to be utilized in preparation for travel. It is • There is no clear evidence for establishing therapeutic goals for patients
always advisable to take extra precautions while traveling to high alti- with SIHG.
tudes (above 8000 ft.) as low oxygen level there may offset glycemic • American Diabetes Association (ADA) glucose targets for patients with
control. While the above guidelines outlined here seem reasonable, there SIHG are not from those with any other type of diabetes.1016 It should be
is no information on how many patients actually have any knowledge of individualized according to life expectancy, comorbidities, patient com-
the basics or seek pretravel counseling, and the area remains largely pliance, and risk of hypoglycemia.
understudied. More data on the diabetic traveling population is needed • In hospitalized patients: a Target glucose range of 140–180 mg/dL is
so that better evidence- based guidelines can be developed. recommended for most critically and non-critically ill patients.
• More stringent goals: 110–140 mg/dL. It may be appropriate for select-
Tips For Safe Trips ed patients if this goal can be achieved without relevant hypoglycemia.
1. Plan your tour well in advance. Consult your physician and discuss it in • In People with COVID-19: < 180 mg/dl1017
detail about tour schedule. Frailty: 120 –200 mg/dl throughout the day1018
2. Carry the prescription, important documents, and a list of all the sup- Care home residents: 126-216 mg/dl
plies at hand. End of life care :106- 270mg/dl
3. Always carry insulin/medicines/accessories double your required • Large blood sugar fluctuations can occur with the use of steroids if the
amount. patient suffers from:
4. Use comfortable shoes; always carry some snacks/ glucose tabs or gel ◦ Severe underlying disease (e.g., cancer),
while on the move. ◦ In the perioperative care setting (e.g., recently transplanted patients or
5. Remain hydrated, avoid unaccustomed food and physical activities, those requiring steroids as supportive therapy
and avoid alcohol in excess. ◦ Those who receive concomitant complex therapies (chemotherapy, im-
6. Always take help from co-travelers or travel agents in an emergency. munosuppressants, etc.)
Background
Steroid-induced hyperglycemia Glucocorticoids increase insulin resistance, leading to hyperglycemia, in
diabetic and non-diabetic patients. Steroids are used for their anti-
Recommendations inflammatory property to treat a variety of conditions in both inpatient
and outpatient settings. It is challenging to manage steroid-induced hy-
Recommended care1014,1015 perglycemia (SIHG) as there are no clear recommendations from various
• Consider screening for glucocorticoid-induced diabetes should be in all societies due to the paucity of data.
those treated with medium to high doses of glucocorticoids. SIHG is defined as abnormally elevated blood glucose associated with the
use of glucocorticoids in patients with or without pre-existing diabetes
• If there is no previous diagnosis of diabetes mellitus. Oral glucocorticoid use is linked to 2% of cases of new-onset
◦ Prior to the commencement of steroids, check Hb1Ac in individuals diabetes mellitus globally in a 2006 study.1019 The prevalence of steroid
perceived to be at high risk. use in people with diabetes in hospital in-patients varies between 25-40%
◦ Once steroid initiated, recommend capillary blood glucose (CBG) once of the population.1020 The diagnostic criteria for SIHG are the same as in
daily. It should be done pre or post-lunch or evening meal, in those at high other types of diabetes, but diagnosis is reasonably challenging in patients
risk or with symptoms suggestive of “hyperglycemia”. with SIHG. One important reason is as fasting blood glucose might be
◦ If CBG is below 216mg/dl, we consider it at low risk and then record the normal if short- or intermediate-acting glucocorticoids are administered in
capillary blood glucose daily post breakfast or post-lunch single morning doses. If an oral glucose tolerance test is performed in the
◦ There is no need for capillary blood testing if the value is consistently morning hyperglycemia might be absent after glucose exposure as the
less than 180 mg/dl. diabetogenic effect of the glucocorticoids is not yet present. In those with
◦ Increase the testing frequency to four times a day if the value of capillary new-onset glucocorticoid therapy, HbA1c might be inconspicuous. It is
blood is found more than 216 mg/dl. possible that diabetes can persist and glucocorticoids just unmasked a pre-
◦ Consider treatment initiation if capillary blood glucose is found to be con- existing glucose metabolism disorder.1021 Acute illness may result in
sistently greater than 216 mg/dl (i.e., on 2 occasions during a 24-hr period) “stress hyperglycemia” independent of steroid administration.1022 Apart
◦ Suh et al. recommend initiating therapy when pre- or post-prandial from activating anti-inflammatory proteins and repressing pro-
glucose repeatedly exceeds 140 mg/dL or 200 mg/dL respectively inflammatory proteins, steroid administration modulates carbohydrate
• If the patient is a known diagnosis of diabetes metabolism. It is via complex mechanisms, including effects on beta cell
Review glucose control and current therapy. function as well as inducing insulin resistance.1023
We must set a target of blood glucose in the range of 106-180 mg/dl.
(Acceptable range 106-216 mg/dl) Management
Start checking capillary blood glucose four times a day and accordingly • Usually, SIHG cases are managed as per strategies to lower glucose in
adjust diabetes medications patients with T2DM.
• Intensification of anti-hyperglycemic therapy should be done
Resource limited considerations • Re-evaluation of SIHG cases should be performed
• If blood glucose remains stable for over 24 hours, monitoring can be • The glucose-lowering agents of choice should match daily glucose
reduced to 3-4 hourly intervals in appropriate cases. profiles.
• If the patient is on parenteral feed, glucose monitoring every 4 to 6 hours • Consider the mechanism of action of glucocorticoid agents to select
is recommended. anti-hyperglycemic therapy.
• Blood glucose monitoring should be more frequent (30 min to every 2 • We don’t have enough evidence for the clinical efficacy of using OHA
hours) if the patient is receiving IV insulin. for in-hospital SIHG cases.
When to use OHA severe or persistent hyperglycemia to high glucocorticoid doses, multiple
• In patients with the stable, non-critical disease and mild hyperglycemic daily or long-acting glucocorticoid use, basal-bolus insulin should be initiat-
excursions, OHAs might be an adequate choice. ed. These regimens offer great flexibility in dose titration.
Choice of antidiabetic1024–1027 Patients Already On Insulin

Table 29: Choices of antidiabetics Patient on short-acting insulin
If hydrocortisone is used, the expectable glucose profile will likely show a fast
and robust increase in sugar but only for a short duration. These transient and
self-limiting glucose peaks require glucose-lowering therapy on a case-to-case
basis. The agent of choice in such a scenario is short-acting insulin (rapid-
acting insulin analogs or regular insulin). It should be injected at the time or
shortly after glucocorticoid administration. Recommended Initiation of the
dose is 0.1 IU/kilogram (kg) bodyweight (BW). Insulin therapy can be inten-
sified by schematic increments of 0.04 IU/kg for pre-prandial values from
200–300 mg/dL or 0.08 IU/kg for values ≥300 mg/dL as insulin requirements
are glucocorticoid dose-dependent, reduction of glucocorticoid is usually re-
lated to an improvement of glycemia. Reduction of rapid-acting insulin should
be performed proportionally to a decrease in glucocorticoid dose.
Patients on intermediate-acting insulin

Intermediate-acting glucocorticoids such as prednisolone and methylprednis-
olone are the most commonly prescribed steroid agents. Having high gluco-
corticoid activity makes them useful for long-term anti-inflammatory and
immunosuppressant treatment. With a single dose administration in the morn-
ing, hyperglycemia develops slowly, but continuously. It lasts until the eve-
ning and gradually recovers until the next morning simultaneously following
the peak and duration of action of the steroid agent. This pattern is suitable for
short- or intermediate-acting basal insulins such as insulin detemir or NPH
(neutral protamine Hagedorn). A clinical recommendation to initiate insulin
with a dose of 0.4 IU/kg of NPH insulin is warranted. If the patient is on
multiple daily administrations of intermediate-acting glucocorticoids, hyper-
glycemia might overlap and persistent hyperglycemia can occur. In this sce-
nario, NPH insulin once daily will not be sufficient. Switch to NPH twice
daily or switch to longer-acting insulin (e.g., glargine). If necessary, add rapid-
acting insulin boluses.
Patients on long-acting insulin1031,1032

Dexamethasone has a prolonged duration of action lasting for more than 24
h. Hyperglycaemia in association with long-acting glucocorticoids, de-
velops slowly, peaks during the day (varying time points) and is sustained
for 24 h after intake. Generally, intermediate-acting basal insulins (NPH
insulin, insulin detemir) should be prescribed twice daily (an initial dose of
0.3 IU/kg BW). Alternatively, long- or ultralong-acting basal insulin ana-
logs (insulin glargine U100/U300 or insulin degludec) might be the most
appropriate insulin to control hyperglycemia in this situation (initial dose
0.2 IU/kg BW). No data exists for new generation ultra-long-acting basal
insulin analogs for the treatment of SIHG. In the recent COVID-19 pan-
demic, dexamethasone use was justified in the appropriate situation.
Covid, Steroids, And Hyperglycemia
administered, the total dose of NPH

insulin can be divided or substituted for
long-acting basal insulin (insulin detemir
or glargine).
Patients with significant hyperglycemia and severe illness1028–1030

Insulin remains the treatment of choice in the hospital setting. The insulin
therapy chosen for SIHG must take into account the user agent, the current
dose, the time point, and the interval of the glucocorticoid administration into
account. It is a good practice that in patients with pre-existing T2DM already
requiring insulin, a 20% increment in daily insulin dose is required upon the
addition of glucocorticoid therapy to achieve similar glycaemic control. Oral
hypoglycemic agents can be added to insulin therapy when patients continue
to exhibit severe or persistent hyperglycemia (HbA1c >9%). In patients with
After Discharge
Tapering is not required if steroids have been used for short duration.1033
After steroid therapy, monitoring of blood sugar is continuously warrant-
ed as we anticipate pre-steroid blood glucose levels after stopping anti-
hyperglycaemic medications. Test Hb1Ac after 3 months post steroid
therapy.
Diabetes And Pregnancy
Table 30: Different corticosteroids and their equivalent doses, steroi-

dal kinetics and potential to trigger hyperglycemia.
Hyperglycaemic Effects
Peak (Hours)
Equivalent Half- Duration
concentrat
Glucocorticoids dose Life Of action
ion
(Approx.) (Hrs) (Hrs) Onse Resolutio
(minutes)
t Peak n
Hydrocortisone
20 10 2 08-Dec 1 3 6
(Short acting)
Prednisolone
Methylprednisol
5 60-180 2.5 12-36 4 8 12-16
one
4 60 2.5 12-36 4 8 12-36
(Intermediate
acting)
Dexamethasone Variabl Limited Care

0.75 60-120 4 36-72 8 24-36
(Long acting) e
• Delay surgery until fluid volume status (BUN, creatinine, and urine output) is stable
and metabolic (pH, plasma glucose, creatinine, BUN, electrolytes) control is achieved.
• Tailor the postprandial insulin requirements according to the nutritional mode of
patient.
• Avoid consecutive doses of subcutaneous insulin to prevent “stacking” of insulin.
Recommended Care
Background
• Conduct preoperative assessments: baseline history of diabetes, assessment of Patients with diabetes experience a higher number of hospitalization and
microvascular and macrovascular complications, HbA1c, serum electrolytes and surgeries with longer hospital stays, higher treatment costs and greater
creatinine level, and current treatment regimen. risks of morbidity and mortality than non-diabetics. [798-800] Surgeries in
• Maintain serum glucose of 140-180 mg/dL for all in-hospital patients (ICU and for patients with diabetes can be categorized as major or minor. Major inpa-
general care medical and surgical wards). tient surgeries are defined as procedures requiring general, epidural, or
• Sulfonylureas, meglitinides, TZDs, GLP-1 agonists must be discontinued on the day of spinal anesthesia for ≥1 h and hospitalization for >1 day, while all other
surgery and metformin should be discontinued a night before surgery. outpatient procedures may be defined as minor surgeries. [801,802]
• SGLT-2i should be discontinued 3 days prior to surgery. Surgical procedures may result in a number of metabolic perturbations
• In patients undergoing surgery, insulin basal-bolus regimen should be preferred. that can alter normal glucose homeostasis. Persistent hyperglycemia be-
fore and during surgical procedures may lead to postoperative complica-
• For longer and complex surgeries IV insulin infusion is recommended. tions like cerebral ischemia, endothelial dysfunction, postoperative sep-
• Monitor blood glucose more frequently ranging from 0.5-2h sis, acute renal failure and surgical site infection (most common compli-
• On the day of surgery, avoid alterations in long-acting basal insulin unless there is a
cation) and may also impair wound healing in patients with diabe-
tendency of hypoglycemia or if the patient is on diet restriction preoperatively. tes.[803,804] Surgical stress may lead to hyperglycemic hyperosmolar syn-
drome (HHS), the most common postoperative complication associated
with 42% mortality rate along with diabetic ketoacidosis (DKA) during or
• Basal insulin only after surgery.[802,803,805] Furthermore, increased stress leads to increased
counter regulatory hormones causing insulin resistance and the resulting
• • Once-daily dosing – Patients with type 2 diabetes who take only once-daily basal
hyperglycemia impairs neutrophil function and triggers overproduction
insulin (e.g., NPH, glargine, detemir, degludec) may continue basal insulin without
any change to their usual regimen, as long as the basal insulin dose has been adjusted
of inflammatory cytokines and reactive oxygen species which causes
vascular and immune dysfunction, and cellular damage.[804] Therefore,
to minimize these negative consequences and improve the postoperative
outcomes it is important to carefully manage the glycemic level in dia- Preoperative management
betic patients undergoing major surgeries, including orthopedic and car- Patients treated with oral medications and/or noninsulin injectable Metformin
diac.[805] The treatment recommendations for patients with T2DM should should be discontinued a day before surgery due to the possibility of lactic
be individualized-based on the severity of diabetes, their usual standard acidosis with mortality rate of approx. 50%.[807] OADs mainly sulfonylureas
diabetes regimen, level of glycemic control, and types of surgical proce- and meglitinides, in fasting state have potential to cause hypoglycemia and
dures (major/minor).[802] Overall, the management goal in diabetic pa- trigger endogenous secretion of insulin, independent of the glucose level,
tients undergoing surgery should be optimization of metabolic control, hence should be discontinued one day before surgery. Further, sulfonylureas
adequate fluid repletion and postoperative care management with or with- and meglitinides increase the risk of myocardial ischemic injury and may be
out insulin to improve surgical outcomes. [798,804,805] associated with an increased risk of cardiovascular events and mortality.[808]
SGLT-2 inhibitors are associated with high risks for DKA and volume de-
Preoperative assessment pletion. There have been many case reports of euglycemic ketoacidosis in the
Early risk assessments can minimize the incidence of perioperative and perioperative setting; hence, SGLT-2 inhibitors should be stopped three days
post-operative morbidities and reduce mortality rates as it provides an prior to surgery. [809-811]. DPP-4 inhibitors may be discontinued before sur-
opportunity for planned intervention, proper arrangement, and long- gery; however, a recent study establishing the safety and efficacy of sitaglip-
term follow-up.[799] Physicians and multidisciplinary care teams must tin alone or sitagliptin in combination with basal insulin in hospitalized med-
comprehend a strategic plan to optimize glycaemic management in dia- ical and surgical patients demonstrated good tolerability and low risk of
betic patients undergoing surgery.[806] hypoglycemia and can be considered a viable option in the perioperative
Perioperative glycemic targets and assessment preoperatively, the ADA setting.[806,812] Due to slow gastric motility, GLP-1 agonists (exenatide, lirag-
recommends a preoperative glucose target of 80 to 180mg/dL as reason- lutide) are usually withheld the day before surgery.[809,813] AGIs (acarbose,
able blood glucose maintenance. It is mandatory that the preoperative miglitol) lower glucose absorption after meals, but these agents do not have
evaluation for surgical procedures must be conducted and must include any effect in the preoperative fasting states, and hence should be discontinued
an assessment of glycemic control and the presence of any diabetes- until the patient resumes eating.[816] TZDs should be avoided due to risks like
related complications. The critical baseline laboratory data must be congestive heart failure, fluid retention and peripheral oedema.[812]
assessed to measure serum creatinine level to assess DKD, hemoglobin
HbA1c, and blood glucose level.[806] Other critical assessments that must Patients treated with insulin
be considered are enumerated below [Table 24]. Insulin being the most preferred choice of drug for patients undergoing sur-
gery, the basal-bolus regimen is the best protocol as it is associated with
What is specific managemant of diabetes in surgical patients with improved glycemic control and lower perioperative complications.[807]
diabetes? Continuing at least part of the basal insulin is the reasonable, physiologic
The specific management‚ of surgical diabetic patients will depend on approach to controlling glucose levels before surgery in patients with diabetes.
whether the patient is: Basal bolus regimens are also associated with reduced postoperative compli-
• On diet alone/ OHA/Insulin therapy cations and reduced inpatient costs per day. The dose of usual basal insulin
• Blood glucose level controlled/uncontrolled can be reduced by 20-30% if the patient reports nocturnal or fasting hypogly-
• Undergoing Major/Minor surgery cemic history.[817] Long-acting insulins demonstrate fewer peaks and hence
• Undergoing elective/emergency surgery do not result in hypoglycemia during fasting. It is advised that long-acting
insulins must be taken as close as possible to the usual injection time, preop-
Major surgery is defined as any operative procedure under general anes- eratively. The intermediate-acting insulin neutral protamine Hagedorn (NPH)
thesia for convenience. Management of diabetes will be discussed in is usually given two times daily. NPH is not a peak less insulin, and there is a
various hypothetical groups, which is likely to be encountered in daily chance of hypoglycemia and better be avoided in these settings. Premixed
practice. insulins (Combinations of basal and prandial insulin) are not recommended
A. Type 2DM/ diet alone/ minor before the surgery.[818] Patients on insulin pumps subjected to longer surgical
• No specific change in preoperative therapy is required if patient is able procedures should be shifted to the IV insulin infusion. Patients on basal-bolus
to eat his regular meals. insulin regimen should calculate the total daily insulin dose [Table 25].[803]
B. Type 2DM / OHA/ controlled/ minor
• Again no specific preoperative therapy change is required if the patient Intraoperative management
can eat his regular meals and take drugs. However, monitor blood glu- Endocrine Society and Society for Ambulatory Anesthesia (SAMBA)
cose levels perioperatively and if hyperglycemia (blood glucose >200 recommend that intraoperative glucose levels be maintained at less than
mg/dl) occurs insulin infusion can be started as described below. 180 mg/dL. Glucose levels should be monitored hourly intraoperatively
C. Type 2DM / OHA/ controlled/major/elective and immediately after surgery. [812,819] For patients with T2DM undergo-
• These patients if on long acting OHA, required to be changed to short ing major or minor surgery, IV infusion of insulin, glucose, and potassi-
acting OHA. Metformin should be discontinued 48 hours prior to and um is recommended to maintain the glycemic targets [Table 26].[802] To
48 hours subsequently to the procedure to protect against possibility of maintain the glucose targets intraoperatively, IV insulin infusion
metformin induced lactic acidosis, risk of which in increased during regimen-a protocol-driven algorithm is recommended.[806]
hypotension and increased anaerobic metabolism. A simple protocol
is described below. Postoperative management
Avoid long-acting OHA (Glimeperide) Glucose control in noncritically-ill, non-ICU surgical patients is managed
If on glibenclamide/ glipizide/ gliclazide with subcutaneous insulin. During recovery, the glucose levels must be
1. Omit the morning dose on the day of operation monitored at least every 2-h for all diabetic patients and non-diabetics
2. Monitor blood glucose treated with insulin in the operating room. Correctional subcutaneous
3. Control hyperglycemia with insulin infusion rapid-acting insulin doses are provided for BG greater than 180mg/dL
4. Restart OHA when oral diet is resumed Patient should be transitioned to a subcutaneous basal/bolus insulin reg-
D. Type 2DM / OHA/uncontrolled/ major/elective OR imen as soon as the patient can consume solid food. To prevent the insulin
Type 2DM / Insulin treated/major/elective undergoing any surgery These coverage gap while transitioning from IV infusion to subcutaneous, after
patients will require insulin therapy perioperatively for the control of administering the first subcutaneous insulin dose, there should be infusion
hyperglycemia and to avoid surgery-related complications. overlap for at least 1-2-h. Patients previously on an insulin regimen can
continue their regular dose provided they are good with eating patterns.
For patients not on insulin treatment previously, depending on the pa- Table 33: Intravenous insulin infusion protocol
tient’s sensitivity to insulin calculate a subcutaneous regimen by totaling
0.2-0.5 U/kg of body weight. The total calculated daily insulin dose is to Initiate insulin infusion by mixing 100 U short-acting insulin + 100 mL normal saline at the rate of 0.5-1 U/h (0.5-
1 mL/h) a. Initiate separate infusion of 5% dextrose + water at the rate of 100-125 mL/h. Monitor BG every hour
be divided as 50% basal component (long-acting insulin) + 50% prandial (every 2 h when stable) and according to the following algorithm adjust the insulin infusion rate
boluses (rapid-acting insulin) and split between breakfast, lunch, and
dinner. Patients treated with oral/non-insulin injectables initiate their reg- BG level Action
ular home regimen provided they are regularly eating and are medically (mg/dL)b
stable. Do not resume metformin for at least 2-3 days, especially in pa-
<70 Recheck BG after turning off infusion for 30 min. If reading still shows
tients with renal dysfunction, hepatic impairment or heart failure because <70 mg/dL, give 10 g glucose and keep checking BG every 30 min until
of potential risk of metabolic acidosis. [806,812] the level rises to 100 mg/dL, resume the infusion and reduce rate by 1 U/h
70-120 Reduce insulin infusion rate by 1 U/h

Table 31: Preoperative assessments
120-180 Continue the regular insulin infusion
History Physical assessment Baseline assessment

181-250 Increase rate of insulin infusion by 2 U/h
Asses for symptoms of neurologic, Examine BP, feet, skin Assessment of serum
cardiac, retinal, renal and PVD Family (insulin-injection site), electrolytes and creatinine 251-300 Increase rate of insulin infusion by 3 U/h
history of diabetes, nutritional status, thyroid. Cardiac level, HbA1c (if not
eating pattern, weight history, previous examination including assessed since last 3 301-350 Increase rate of insulin infusion by 4 U/h
or current infection, use of alcohol, resting tachycardia, months) and BG level
tobacco etc. orthostatic hypotension,
351-400 Increase rate of insulin infusion by 5 U/h
stress test or angiography as
indicated Identification of
comorbidities and >400 Increase rate of insulin infusion by 6 U/h
Endocrine disorders, history of acute
optimize wherever
hypoglycemia, ketoacidosis. Type and
Airway, neurologic and required with the help of a
duration of diabetes, current treatment abdominal examinations multidisciplinary team
regimen along with diet and results of
glucose monitoring
Prepare an infusion syringe by adding 50 units of insulin to 50 ml of
normal saline (1 ml = 1 unit of insulin).
1. Initial rate of insulin infusion and bolus is calculated by measuring the
BP: Blood pressure, Glycosylated hemoglobin, blood glucose and dividing the value by 100 (round off to the nearest
PVD: Peripheral vascular disease, BG: Blood glucose whole number or0.5 fraction).
2. Monitor blood glucose hourly and adjust the dose according to the
above formula.
Table 32: Supplemental insulin dose adjustment
3. If blood glucose falls >100 mg/ dl or >20% of the previous level in the
first hour, then decrease the calculated insulin dose by 0.5 -1.0 unit.
BG (mg/dL) Usuala Insulin-sensitiveb Insulin-resistantc 4. If blood glucose does not fall by 50 mg or 10% of the previ-
ous level within 2 hours of starting insulin infusion, then increase
>141-180 4 2 6 the calculated insulin dose by 0.5-1 unit. Maximum limit is 50
units/hour.
181-220 6 4 8
5. When blood glucose is <100 mg/ dl, stop insulin drip or pump
for 60 minutes. Add 5% dextrose @75-100ml/ hr. Measure blood
221-260 8 6 10
glucose after 60 minutes. Restart insulin infusion when blood
glucose >100
261-300 10 8 12
301-350 12 10 14
351-400 14 12 16
>400 16 14 18
Numbers in each column represent the number of regular or rapid-acting insulin analogs per
dose. Add the “supplemental” dose to the scheduled insulin dose. aGiven before each meal and at
bed-time for the patients able to take all or most of his meals, bStart regular insulin every 6 h or
rapid acting insulin every 4-6 h for the patients who are elderly, not eating and with impaired
renal function, cIn patients receiving more than 80 U/day before admission and those who were
receiving corticosteroids. BG: Blood Glucose
FASTING AND DIABETES clinical manifestation of diabetes is required to design strategies for gly-
Recommendations cemic management during fasting.1041
Table 34: Types of fast
Complete fasting: Giving up food and water

completely for a period
Partial fasting: Eating less than you need to

avoid hunger
Limiting the number of food items eaten
Giving up favorite foods
modified nutrition plan designed for fasting with regular glucose monitoring and adjustment
of treatment regimens is recommended.
Figure 18: Structured education program
Background Table 35: Factors to be modified

Fasting is just not merely abstaining from food or ‘starving’, it is defined as
the ability to meet the body’s requirements for vital nutrients during either Fasting Antidiabetic Individual Patient
agents phenotype characteristic
shortage or absence of food, by utilizing the body’s energy reserves without s
jeopardizing health and wellbeing.1034 Periodic voluntary fasting, is a com- Duration of fast Potential for Risk of Preg
mon religio-cultural practice adopted by individuals from various religions Restriction of hypoglycemia hypoglycemia nanc
across the world for centuries as a crucial pathway of spiritual purifica- fluids/solids: Potential for Risk of y
absolute/partial dehydration hypoglycemia Elde
tion.1035,1036 Fasting or food abstinence, initiates metabolic and psycholog- Frequency of fast Potential for unawareness rly
ical changes and adaptations that need close monitoring, primarily in pa- (once weekly/once gastrointestinal Ability to self- Concomitant
tients with derailed metabolism. Therefore, individuals with diabetes or pre- monthly/once upset monitor BG diseases
diabetes must fast only after an appropriate risk assessment and counseling yearly/others) Duration of action Adolescent
with healthcare practitioners (HCPs) as well as religious leaders and make and children
an informed decision.1034,1037 In individuals with diabetes, insulin resis-

tance and/or deficiency can lead to excessive glycogen breakdown and a BG: Blood glucose
surge in gluconeogenesis or ketogenesis leading to sudden hyperglycemia,

diabetic ketoacidosis, dehydration, and thrombosis.1037 Furthermore, in The different religious fasts commonly observed in India that can have a
special populations like pregnant women, geriatric patients and individuals significant impact on metabolic and glycemic health in diabetes is
with comorbidities (such as cardiac, renal or hepatic impairment), fasting • Ramadan fasting: It is a principal ritual followed by Muslims during the
may increase the risk of complications if appropriate care is not taken.1038– sacred month of Ramadan (the ninth lunar month of the Islamic/Hijri
1040
Therefore, a patient-centric approach with appropriate diet plan and calendar).1044 During this month, all healthy adult Muslims abstain from
appropriate adjustments in pharmacotherapy with careful glucose monitor- food, drinks, and medication from dawn to dusk (sunset). Believers
ing during fasting period may reduce the complications in people living usually eat two meals, one before dawn (Suhur) and one after sunset
with diabetes. Depending on the degree of abstinence from food, fasts may (Iftar). Hypoglycemia and dehydration are major complications associ-
be classified as follows [Table 32]. ated with fasting though hyperglycemia may occur, due to overindul-
gence in food during meals12,13 Therefore, pre fast risk stratification,
Religious fasts followed by a treatment tailored to individual needs appears to be the
Although religious fasts seldom exceed 24 h, the variability of the dura- best management strategy. In addition, structured education enables
tion of every phase may lead to different physiological responses to patients to self-manage their condition better.1043–1045
fasting particularly in people living with diabetes.1041 Though several • Hindu fasts: Though not mandatory, most Hindus observe day-long and
guidelines are available for different aspects of diabetes care, fasting in week-long fasts. Karva Chauth, Guru Purnima, Ekadashi, Makar Sakranti
diabetes poses a unique challenge.1042,1043 Additionally, designing ran- and Holi Ashtami are some of the annual, monthly and weekly fasts ob-
domized controlled studies to address fasting-related issues in patients served as part of various vows. During Navratri, which occurs twice a year,
living with diabetes is particularly difficult. Therefore, understanding Hindus observe fast for 9 days usually from dawn to moon- rise/star-rise.
the physiology of fasting [Figure] and linking it to pathophysiology and The day-long paryushan of Hindu fasts however makes it distinct from the
month-long fasts of Ramadan and Buddhist Lent. Unlike Islam, there are fasting without medical advice and experiencing events suggestive of
no universal rules laid down for Hindu fasts, and therefore data on meta- hyperglycemia, hypoglycemia and dehydration. Therefore, educational
bolic effect of these fasts are scanty thus far.1046,1047 interventions by HCPs prior to Ramadan can help in creating awareness
• Jain fasts: During the pious month of Paryushana (eight days for the among patients and can help them in making rational decisions about
Shwetambar sect, and ten days for the Digambar sect), Jains usually fast control of diabetes during Ramadan. 1054
from dusk to dawn unlike Hindu fasting which extends from dawn to • Self-monitoring of blood glucose (SMBG) and Continuous blood glu-
moon- rise.1036 cose monitoring(CMBG) should be considered as an important tool that
helps both patients and physicians to practice safe decision-making
Considerations regarding drug dosage and other aspects of management.1055
Based on the following factors the glucose-lowering therapy/ strategy • Patients who received individualized education are more likely to modify
during the fasting period may be modified/altered [Table]. their diabetes treatment plan during Ramadan, perform self-monitoring of
blood glucose at least twice daily during Ramadan, and have improved
knowledge about hypoglycemic signs and symptoms as compared to pa-
Rationale And Evidence tients who followed the standard diabetes management protocol.1056
General • Real-time continuous glucose monitoring by offering constant 24-hour
Complete abstinence from food and drink between sunrise and sunset can recording may improve patients’ safety during fasting. Flash glucose mon-
have a significant impact on homeostasis. Since the majority of diabetic itoring may be a valuable tool in clinical practice during Ramadan avoiding
individuals are asymptomatic, they are unaware of the potentially delete- multiple painful finger-pricks in addition to potential of unlimited monitor-
rious effects of diabetes, particularly during religious fasts. Additionally, ing times. In children and adolescents with T1DM who used flash glucose
conditions of complete abstinence from food and/or water during reli- monitoring during Ramadan, the risk of life-threatening episodes of severe
gious fast can lead to skipping medications, resulting in worsening of hypoglycaemia or diabetic ketoacidosis was low. 1057
their glycemic control. • Studies have shown that pre-Ramadan counselling reduces episodes of
• An observational study in Muslim patients with diabetes fasting during low blood glucose. Pre-Ramadan education provides a platform to re-
Ramadan reports that 59% of patients had substantial knowledge of mind people with diabetes about the importance of diet and exercise,
diabetes, 37% of patients did not monitor their blood glucose levels and that regular glucose monitoring is essential to avoid complications,
during the previous Ramadan and 47% had hypoglycemic episodes.1048 while reassuring them that this does not invalidate the fast. The IDF-
• In a prospective clinical study conducted in Iran the glycemic control DAR Practical Guidelines provide healthcare professionals with both
deteriorated significantly among T2DM patients who opted to fast dur- background and practical information, as well as management recom-
ing Ramadan however the HbA1c levels reduced significantly follow- mendations to optimise the care delivered to people with diabetes who
ing the month after Ramadan.1049 plan to fast during Ramadan.1058
• In an Indian study conducted in 50 patients having type 2 diabetes at a
dedicated diabetes care centre, fasting during Ramadan was associated Lifestyle modifications and Nutrition during fasting
with a reduction in body weight, body mass index & HbA1c level in all • Fasting or healthy abstinence from food is a form of lifestyle modifica-
patients irrespective of baseline pharmacotherapy but this reduction was tion for T2DM patients and if utilized appropriately, may result in sev-
statistically significant only in patients taking metformin with DPP in- eral health benefits for these patients.1059
hibitors and/ or SGLT2 inhibitors as compared to patients taking insulin • Pre-fasting diet should include slow-release foods and patients with
or sulphonylureas at baseline.1050 T2DM should not indulge in over-eating in the post-fasting period in
• In a study conducted in Pakistan in 78 patients having diabetes who order to avoid postprandial hyperglycaemia.1059 Therefore, complex
fasted during Ramadan, body weight increased in 36.7% of participants, carbohydrates like whole grains, potatoes, berries, citrus fruits, apples,
decreased in 46.7% with no change in body weight in 16.7% partici- nuts, and legumes at pre-fasting, and simple carbohydrates like bread,
pants . They have also studied the impact of compliance to suggested cereals, rice, and pasta at post-fasting may be more appropriate to re-
nutrition plan on body weight changes. In participants complaint to duce complications.1044
suggested nutrition plan, no weight change was observed in 25% while • During prolonged fasting periods like Ramadan or Navaratri, physical
66.7% had decreased and 8.3% had increased their weight significantly activity should be restricted. While routine exercise can be continued,
by a mean of 1.8 kg. However in non-complaint participants, no weight elective moderate to highly vigorous exercise should be rescheduled but
change was observed in 33.3% while only 11.1% had decreased and 56 total bed rest should be avoided.1046
% had increased their weight significantly by a mean of 2.7 kg.
Therefore compliance to suggested nutrition plan is essential for diabe- Pharmacotherapy
tes management during Ramadan.1051 • Individualized or bespoke treatment choices must be made for oral
agents during the fasting period.1060 Antidiabetic agents that improve
DM Education insulin sensitivity must be chosen as the risk of hypoglycemia is signif-
Concerned physicians and HCPs may play a critical role in educating icantly lower.1043
patients with diabetes during fasting [Figure 19]. Patients and their fam-
ilies should be included in a structured diabetes education program, which Metformin
provides information about risk stratification, nutritional advice, physical Biguanides (Metformin) is generally considered safe in patients with
activity, glucose monitoring, identification and management of hypogly- diabetes during fasts due to minimal incidences of hypoglycemia, how-
cemia, dosage and timing of medications, and identification of the warn- ever, once daily dosing needs to be adjusted or modified to avoid com-
ing symptoms & signs of complications.1052 plications.1061 Slow-release formulations of metformin must be taken
once daily following the sunset meal.1062
• Implementation of the Ramadan Education and Awareness in Diabetes Sulphonylureas and Guinides
(READ) program led to significantly lower weight gain (p<0.001) and Sulphonylureas (new generation: gliclazide MR and glimepiride) should
hypoglycemic episodes (p<0.001) with reduced risk of acute complica- be preferred over older, long-acting sulfonylureas like glibenclamide and
tions compared to those who were not educated during fasting.1053 chlorpropamide during Ramadan fasting, as they are relatively more safe
• As per the survey-based study carried out in India, there was lack of and economical.1042,1045,1063,1064 Despite a reduction in dose during
knowledge and awareness about diabetes and impact of fasting on it Ramadan fasting, Glibenclamide was associated with a high incidence
among patients living with diabetes resulting in a large number of them of hypoglycemia due to its longer duration .1042Despite a reduction in
dose during Ramadan fasting, Glibenclamide was associated with a high • In a multinational, randomized, treat-to-target trial in patients with
incidence of hypoglycemia due to its longer durationof action and high T2DM who fasted during Ramadan, insulin degludec/insulin aspart
affinity for its binding receptors. 1065 In two prospective multicentric coformulation (IDegAsp) was having similar glycaemic efficacy as
international randomised trials, gliclazide was demonstrated to have same biphasic insulin aspart 30 (BIAsp 30)but with significantly less
incidence of hypoglycemia like sitagliptin during Ramadan fasting. overall,daytime and nocturnal hypoglycaemia. Therfore IDegAsp is a
Therefore it is safer to use either gliclazide or short acting repaglinide suitable therapeutic agent for patients who need insulin for sustained
during Ramadan.1065 glucose control before, during and after Ramadan fasting. 1076
• As per SOUTH Asian consensus guidelines, Insulin degludec and
DPP-4 IDegAsp should be considered drugs of choice for use as basal and dual
Thiazolidinediones (pioglitazone) are generally regarded as safe during action insulin before and during Ramadan and IDegAsp can be injected
Ramadan, however, it may lead to an increase in body weight. There is with meals, once daily(depending upon the major meal; either iftar or
only 1 study supporting the use of pioglitazone during Ramadan.1065,1066 suhur) or twice daily, or once daily along with an extra dose of insulin
Alpha-glucosidase inhibitors: No RCTs are available about AGI use dur- aspart. 1077
ing fasting currently. However, because of their insulin independent
mechanism of action and negligible risk of hypoglycemia, they can be Table 36: Approach to adjustment or modification of continued anti-
safely used without any dose adjustment during the fasting period.1067 diabetic medications in patients with diabetes during fasting period 1075
• Incretin based treatments may maintain adequate glycemic control in a
glucose-dependent manner, thus providing a safe alternative therapeutic
option during Ramadan1043
• Vildagliptin was found to be effective, safe, and well tolerated in T2DM
patients fasting during Ramadan, with a consistently low incidence of
hypoglycemia across studies, accompanied by good glycemic and
weight control.1068
• Switching anti-hyperglycemic treatment to sitagliptin from a sulfonyl-
urea reduced the risk of symptomatic hypoglycemia by approximately
50% in patients who fasted during Ramadan.1069
• In Treat 4 Ramadan trial, liraglutide compared with sulfonylurea was
well tolerated with more patients achieving target HbA1c, losing or
maintaining weight with no severe hypoglycemia, and with a high level
of treatment satisfaction.1070
• Contrary to the Treat 4 Ramadan trial, no significant difference between
liraglutide and sulfonylureas in terms of severe hypoglycemia.
However, significant, weight loss and HbA1c reduction (p<0.0001)
was observed in the liraglutide group suggesting that liraglutide may
be considered an effective therapy in combination with metformin dur-
ing Ramadan.1071
SGLT-2i
Sodium-glucose cotransporter 2 inhibitors may be used during fasting, in
view of their low risk of hypoglycemia. However, the potential risk of
dehydration must be considered. Because of beneficial impact of SGLT2
inhibitors on body weight & hypoglycemia, they can be considered for
use during fasting but the potential risk of adverse events related to
volume depletion, euglycemic ketoacidosis as well as genitourinary in-
fections and additional risk of falls in elderly due volume depletion in
fasting should be kept in mind.
• Treatment with dapagliflozin was associated with fewer incidences of
hypoglycemia than sulfonylureas (p=0.002).1072 Table 37: Dose adjustment/modifications for the management of
• A recent survey report conducted on physicians highlights that SGLT2 T2DM during Ramadan fast
inhibitors are safe and effective for T2DM management during
Ramadan and (92.2%) of physicians suggested prescribing SGLT2 in-
hibitors with the first evening meal (Iftar).1073
• Till date, there are 3 reported studies about SGLT2 inhibitors use during
Ramadan showing beneficial effects on HbA1c, BP and body weight.
However, postural hypotension, dry skin and UTI were more common
with their use. But ketonemia and deterioration of renal parameters were
not observed thereby suggesting safety of these agents during
Ramadan.1065
Insulin
• Use of a rapid-acting insulin analog instead of regular human insulin
before meals in patients with T2DM who fast during Ramadan was
associated with less hypoglycemia and fewer PPG excursions.1074
• Insulin analogues (basal, prandial and premix) are generally preferred
over regular human insulin mainly to minimize the risk of
hypoglycemia.1075
Special Population Table 38: Categories of risk in patients with T1DM or T2DM who
Pregnant Patients fast during Ramadan
Many pregnant women with pre-existing diabetes or GDM are considered as
high-risk group for fasting. Multiple factors influence the risk assessment of a
pregnant women with hyperglycaemia and these should be carefully re-
viewed prior to fasting. Patient education prior to is essential to ensure mother
and foetus safety regardless of fasting decision. Regular SMBG should be
conducted and at the very least once before the sunset meal; 1-2 hours after
meals; once while fasting; anytime feeling unwell. Pregnant women must
understand that regardless of their fasting status, they need to sustain the
standard blood glucose targets during pregnancy of:
• Fasting between 70-95 mg/dL (3.9 – 5.3 mmol/L).
• Post-prandial < 120 mg/dL (6.7 mmol/L).
Pregnant women must also understand that during pregnancy they should
break their fast if any of the following occur:
• Pregnant women must break their fast if they feel unwell; BG levels
drop below 70 mg/dL (3.9 mmol/L); or identify a reduction in foetal
movement.
EDUCATION
• Patients treated with insulin should have doses adjusted according to
Recommendations
their insulin regimen. 1058
Recommended Care
Patients with T1DM
As per the current recommendations, patients with type 1 diabetes • A patient-centered, structured diabetes self-management education (DSME) is
mellitus are considered as high-risk to very high-risk for fasting; and recommended as an integral part of the care of all people with T2DM.
therefore, it is prudent to avoid unsupervised fasting in type1 • The diabetes self-management education and support (DSMES) program should be
diabetes. But with the provision of optimal care (including individualized conducted at least at four critical times: at diagnosis, annually, when complicating factors
care, provision of flash glucose monitoring, structured Ramadan and arise, and when transitions in care occur, and as considered appropriate.
• Medical professionals can conduct education programs, and certified diabetes educators
diabetes education sessions and access to a specialist diabetes center), who are quality assured can provide education (Certified Diabetes Educators) in groups
selective patients with type 1 diabetes may fast during Ramadan safely or individual settings. A family member, friend, or caregiver may be involved as needed.
with a low rate of complications including hypoglycemia as per one study • The education program should focus on people with diabetes from all backgrounds,
carried out in UAE. However larger, randomized controlled trials are mainly rural or poorly educated patients, as they may have less knowledge or awareness
regarding diabetes. Education material should be customized for those with diabetes from
required to be able to generalize this as a recommendation.1078
different backgrounds. Every primary care unit should facilitate the training of at least
As per ISPAD consensus recommendations about fasting during Ramadan one of their health professionals to become a diabetes educator.
for young people with type 1 diabetes, limited high-quality data is available • Diabetes education should be focused on assessing changes in patient behaviors and
and therefore well-designed, randomized controlled trials are needed to de- promoting self-management in patients with T2DM.
termine optimal insulin regimens to minimize glucose fluctuations. Currently • Diabetes education initiatives should be in simple, understandable, and local languages as
insulin types and regimens should be individualized as per local resources. far as possible.
Most investigators recommend lowering the insulin dose during fasting but • The healthcare provider should ensure that DSME programs are accessible to all patients
and designed based on considerations of cultural needs, ethnicity, psychosocial status,
recent data do not support this for reduction in the frequency of hypoglyce- medical history, family support, literacy, disability issues, and financial situation.
mia. However, they are optimistic about the recent technologic developments • Use techniques of active learning (engagement in the process of learning and with
such as the newer insulin analogues, “smart” insulin pumps and advanced content related to personal experiences), adapted to personal choices and learning styles.
glucose monitoring devices and telemonitoring which might help young • Use modern communication technologies to advance methods of diabetes education
delivery and channels for intervention such as one-on-one or group sessions and effective
people with type 1 diabetes for safe fasting in the future. 1079
use of social media platforms by creating credible source(s) of information for those
living with diabetes and their caregivers.
Elderly Patients • RSSDI recommends the use of diabetes-related information that is made accessible on
Lower proportions of elderly individuals fast than their younger counter- the official website of RSSDI and associated social media channels, including but not
parts. Diabetes related complications such as hypoglycaemia and limited to Facebook, YouTube, Instagram, and Twitter, for improving knowledge and
offering an empowering tool to bring positive behavior changes and management skills
hyperglycaemia can be more frequent in elderly individuals than in youn- in those living with diabetes and their caregivers. Although limited, the evidence
ger individuals during the Ramadan fast. Greater and more careful plan- suggests that using credible sources is associated with improved patient outcomes.
ning pre-Ramadan is needed in elderly individuals to ensure a safe fast • Provide ongoing diabetes self-management support and the creation of self-help groups.
during Ramadan can be achieved. Preventive education for diabetes and metabolic disorders should start at the school level.
There must be a greater emphasis on SMBG in elderly individuals during
the Ramadan fast to ensure safety.
Antidiabetic drugs with lower risks of hypoglycaemia are preferred in Background
elderly individuals. There is a significant need for more research into Diabetes self-management education (DSME) is a critical component of
elderly individuals with T1DM, T2DM and differing comorbidities that the management of T2DM, facilitating the knowledge and skills required
actively fast during these times.1058 to improve self-care practices to prevent the development or delay of the
Recommendations include: progression of diabetes.1080–1082 Numerous studies report that DSME is
- Increase the frequency of SMBG when fasting before or after meals. associated with improved metabolic control, reduced glycemic levels,
- Consider the using a continuous means of monitoring blood glucose fewer complications, and enhanced quality of life (QoL).1081–1083
levels if available. DSME initiatives aim to improve the knowledge about diabetes and em-
- There needs to be an emphasis on staying properly hydrated, particularly power people with diabetes to make informed choices to self-manage
in individuals prone to diabetes related comorbidities. their condition more effectively.1084,1085 It is guided by evidence-based
- It is important to have an adequate intake of nutrients when breaking the fast. standards while incorporating the needs, goals, and life experiences of
- An individualised nutrition plan should be made prior to fast and ad- patients with diabetes.1086 The 2022 ADA Standards of Medical Care in
hered to during the entirety of it. Diabetes recommends that people living with diabetes should be actively
engaged in education, self-management, and treatment planning with • The world’s first national Gestational Diabetes Mellitus (NGDM)
their health care team, including the collaborative development of an Awareness Day was declared by India on the 10th of March, 2019,
individualized eating plan.923 The 2022 consensus report by ADA and and is observed every year to raise awareness about hyperglycemia in
EASD on the management of hyperglycemia in T2DM recommends that pregnancy and the link between maternal and fetal health with diabetes.
all people with T2DM should be offered access to ongoing DSMES Nationwide, pregnant women are invited to hospitals and clinics for a
(Diabetes self-management education and support) programs.1087 free screening, especially on that day, and educational activities are also
India represents a country with diversity in social, economic, cultural, and held. There are training programs for healthcare professionals, press
educational patterns. The majority of the Indian population resides in rural conferences, awareness-raising events, seminars for women’s groups,
areas, where there may be differing levels of access to information and and widespread screening activities that are conducted on that day.1097
education, resulting in decreased awareness of diabetes as compared to urban • Defeat Diabetes was a massive public-awareness campaign initiated by
areas.1088 No or low literacy in India is a deterrent to a poor understanding of RSSDI with the goal to reach a hundred million people in a hundred
diabetes.1089,1090 Effective patient education is an essential tool, especially in days using various social media platforms of RSSDI and educating
resource-poor settings within India, especially with the rising prevalence of people regarding multiple aspects of diabetes. As part of the campaign,
T2DM across India. Considering the magnitude of diabetes, the increasing a nationwide blood sugar testing camp was conducted, yielding over 1.1
prevalence in the younger generation, and the changing patterns of lifestyle million blood sugar tests in one day. The success of these endeavors
impacting future generations, preventive strategies and education should be highlighted that coordinated, well-executed campaigns, along with the
part of school curricula, workplaces, and offices. use of technology, can successfully create public awareness.1098
Considerations Knowledge and awareness

The panel endorsed the IDF recommendations on education as such. • The ICMR-INDIAB study reported that the awareness of diabetes in
However, evidence from India and local factors such as literacy, nutrition urban India was significantly higher than in rural residents (58.4% vs.
status, body weight, BMI, and financial background was reviewed in the 36.8%, p<0.001). Furthermore, participants from Tamil Nadu had the
Indian context and are considered in the recommendations. highest (31.7) and Jharkhand the lowest (16.3) knowledge score.
Among self-reported patients with diabetes, Maharashtra had the
highest (70.1), and Tamil Nadu had the lowest score (56.5).1088
Rational And Evidence • Similarly, another ICMR-INDIAB study including 14,277 participants
Educational programs and their outcomes revealed that only 480 patients self-reported diabetes (254 urban and
• In managing T2DM patients, a structured diabetes care program (Freedom 226 rural), and the level of glycemic control among patients with self-
365*) with education on diet and lifestyle correction, biochemical investi- reported diabetes in India was poor.1099
gations, clinical monitoring, and treatment at regular intervals was associated • A population-based study from a south Indian state reported that among
with better clinical outcomes compared to routine medical care. The pro- 6211 participants, good knowledge about diabetes was observed in
gram played a pivotal role in improving the patient’s quality of care by 3457 (55.6%) individuals and a positive attitude towards diabetes in a
overcoming clinical inertia and improving adherence to therapy while pre- total of 3280 (52.8%) individuals, respectively. Furthermore, literacy
venting the occurrence/progression of diabetes-associated complications.1091 was significantly associated with good knowledge, attitude, and practice
• Organized diabetes education that involved improving knowledge for in the T2DM population. Overall, women had significantly better
better control of disease symptoms, disease regimens, and risks in prac- knowledge (p<0.001) as compared to men.1100
tice was found to have a positive impact on lifestyle changes, self- • A recent study from east Delhi, India, reported that self-learning mod-
control abilities, and improving the QoL in T2DM patients.1092 ules (SLM) were associated with significantly increasing knowledge on
• A recent systematic review including 118 unique interventions reported that the effect of diabetes on the feet (p<0.05), foot care, and its steps
DSME was associated with a statistically significant mean reduction in (p<0.05) as compared to the control group in T2DM patients.1101
HbA1c levels (-0.74 for intervention and-0.17 for control groups).1081 • Though general practitioners in India are aware and updated about
• A case-control study conducted in the department of medicine of a symptoms and screening for T2DM, there is a dearth of effective ap-
tertiary care teaching hospital in northwest India demonstrated that proaches towards screening and treating complications. Most patients
effective health education improved knowledge, attitude, and practices are usually not advised on non-pharmacological measures or diabetes
leading to better glycemic control that can slow down the progression of education, while interpretation of screening test results or its complica-
diabetes and prevent downstream complications.1093 tions may be controversial.1102
• To minimize the increasing burden of NCDs, the ministry of health and • Evidence from several studies determining the level of knowledge and
family welfare (MOHFW), Government of India, launched the National awareness on diabetes across India suggests that most patients had poor
Programme on Prevention and Control of Diabetes, Cardiovascular diseases knowledge and awareness about their condition.1088,1103–1109 Low socio-
and Stroke (NPDCS) on 8th January 2008, with several objectives includ- economic status, old age, cultural factors, lack of access to healthcare,
ing health promotion and health education for the community.1094 The family history of diabetes, and, importantly, low literacy levels were the
telephone intervention was found to be statistically significant for empow- significant predictors of poor glycemic control among patients with T2DM.
erment and practices of self-care when compared to group education. • A cross-sectional, questionnaire-based survey was conducted on 100 patients
• Besides diabetes, an educational intervention also successfully reduced attending the diabetes unit of a tertiary care teaching hospital in central India.
some of the obesity-related parameters and improved dietary patterns in The majority of these patients were found to be aware of hypoglycemic
individuals with pre-diabetes and diabetes. Initiation of primary preven- symptoms, treatment, and the development of complications. The regular
tion strategies through education right from elementary schools could check-up was done by 70% of patients, while 73% adhered to treatment.1110
reduce IFG by 17%, suggesting such interventions may delay T2DM or • A cross-sectional survey was carried out among participants aged ≥18
even change the course of disease for improved outcomes among vul- years, visiting a tertiary care eye institute in north India to assess peo-
nerable population groups.1095 ple’s awareness about various aspects of diabetes. Of the 530 partici-
• Awareness about early detection and treatment of hyperglycemia in pants interviewed, only 40 (25.6%) individuals with diabetes and 45
pregnancy is also essential, as it is associated with better fetal outcomes (13.8%) without diabetes were aware of diabetic retinopathy. Their
and an improved intrauterine metabolic environment. Interventions knowledge about its risk factors, complications, prevention, and man-
post-partum should be aimed at the long-term prevention of diabetes, agement was poor.1111
obesity, and metabolic syndrome in the mothers and offspring exposed • In a study conducted on 400 diabetic patients (out-patient or admitted),
to intra-uterine hyperglycemia in later life.1096 awareness of diabetic nephropathy was marginally higher in patients staying
in urban areas (vs. rural areas, p=0.120) and among the literate (vs. unedu- wrong perceptions. People with ongoing insulin therapy appeared to
cated, p=0.567) patients. Awareness of diabetic nephropathy was higher in have a better understanding and acceptability of insulin therapy than
older patients (p=0.004) and patients with chronic diabetes (p<0.0001), those who were not on insulin; besides, intensification of insulin therapy
controlled diabetes (p=0.026), and diabetic nephropathy (p<0.0001).1112 remained a challenge in these patients.1123
• Study has shown that pharmacists may also be involved with clinicians as a • Implementing efficacious health service interventions like patient edu-
part of collaborative diabetes care and has documented positive clinical, cation in a real-world resource-constrained setting is not without chal-
humanistic, and economic outcomes, which emphasized the value of mul- lenges and may not prove effective in improving patient outcomes.
tidisciplinary collaborative care for Asian diabetes patients and supported Therefore, interventions must consider patients’ and healthcare pro-
the effectiveness of this approach in managing chronic diseases.1113 viders’ experiences and perceptions and macro-level policies for trans-
• In a review of risks, benefits, and best practices for social media and lation into practice within local health systems.1124
health care providers, it was concluded that social media platforms • In India, due to the disease-related stigma, counseling young and prob-
offered a rich potential for personal and public health promotion and ably unmarried women with diabetes on garnering familial support and
professional advancement when used with discretion. Guidelines issued marital prospects is particularly challenging.1125
by professional societies as well as organizations help health care pro-
viders to prevent the downsides of the use of social media.1114 Assessing the need for evidence-based education 1113,1126–1129
• An evidence-based review of social media use in interventions for diabetes • Appropriately qualified diabetes educators (nurses, dieticians, social
clearly outlined that there was limited good-quality evidence on the use of workers, or qualified diabetes educators) should be a central player in
social media interventions for those living with diabetes; nevertheless, these raising diabetes awareness as part of optimal diabetes care.
platforms are associated with beneficial patient outcomes, and clinicians and • Continuous medical education and periodic training are needed to help
other stakeholders should encourage patients to use the same for knowledge health professionals integrate new knowledge and transform old practices.
enhancement.1115 Findings suggested that the primary intervention support- • Specialized diabetes education should be made accessible to healthcare
ed by social media, especially platforms that are the most popular network- personnel and people with diabetes through various communication
ing sites, improved clinical outcomes for those with T1DM. channels.
• A systematic review of the patients’ use of social media for diabetes self- • General practitioners and physicians should be periodically updated on
care included studies reporting peer-to-peer use of social media for self- recent guidelines related to diabetes, especially on diagnosis, treatment,
care of diabetes and CVD (with stroke) and found that social media use and management goals.
is evolving and offers great potential. Although there were few studies • Key aim of diabetes education is to promote self-management and help
reported so far on social media and diabetes self-care, they reported change behavior for better diabetes management.
interest and demand for peer-to-peer interaction on diabetes self-care. • Given that diabetes is a complex disease impacted by various factors,
The reviewers felt a distinct need to establish the safety and efficacy of empowering language focused on person-first can strengthen communica-
social media use among patients with diabetes and other conditions1116. tion and help motivate good health and well-being in those with diabetes.
• In the pandemic times, patient education gained center stage as self- According to the expert opinion of the task force from the American
management of diabetes was the need of the house. A study evaluating Association of Diabetes Educators (AADE) and the American Diabetes
its use as a platform for education and support for people with diabetes Association (ADA), language for diabetes care and education should be
used “Tweetorials,” “zoom conferences,” and “YouTube videos” and neutral, non-judgmental, and based on facts, actions, or physiology/biology;
found that despite limitations, social media could be effectively used to free from stigma; should be strength-based, respectful, inclusive, and im-
provide reliable, relevant diabetes education and information, especially parts hope and is person-centered. 1130
allowing people to learn at their own pace. 1117 • Awareness and education in diabetes care in India are required to be
improved at the following levels:
Table 39: Recent evidence - Education and need for continuous medical education of physicians,
including family physicians and primary care physicians
Epps A et al., 2019 Whether the use of social media among diabetes specialists across the - Education for people with diabetes, their family, and caregivers.
UK enhances learning on a closed forum, improved communication,
sharing of best practices, and provide peer support. Forum where
- Diabetes education programs in India need to be developed as structured
diabetes specialists shared safety alerts, ideas for service improvement, and regionally applicable.
events, scenarios/medication reviews, updates from conferences, and • Counseling is the most crucial strategy to bring about sustainable life-
job vacancies.
style changes.
• Clinic waiting areas may be used effectively to impart diabetes-related
Challenges in diabetes management in India 1118–1121 education with adequate involvement of family members and caregivers.
• The awareness of the disease and its complications is less than • The components of diabetes education are described in this infographic
satisfactory. and may not be limited to the same.
• There is a lack of knowledge, appropriate attitude measures, or practice • There is also a need to assess the impact of existing education and
studies that can help determine the gaps in knowledge among physicians training programs on diabetes, especially across the Indian diaspora.
and people living with diabetes in India. Physician-related issues, including
inadequate knowledge, delay in clinical response, clinical inertia, and poor
control, need to be addressed through diabetes education for physicians.
• Lack of knowledge among people living with diabetes is a significant
barrier to their ability to self-manage the disease. Hence, having more
structured diabetes education programs in India is imperative.
• Lack of a robust referral system to provide quality and specialist care
and lack of understanding for early diagnosis, prevention, and control of
chronic complications in diabetes. Specialist referral for diabetes man-
agement can be a significant challenge in remote and rural facilities with
primary care and a dearth of trained diabetes specialists.1122 Figure 19: Components of diabetic education. CGM: Continuous glu-
• Indian studies have shown that barriers to insulin therapy partly arise cose monitoring; SMBG: Self-monitoring of blood glucose35
from the lack of awareness, bias, and false beliefs about insulin use and
Implementation Limited Care

• Major components of implementing the recommendations are the re-
• Be alert to signs of cognitive, emotional, behavioral and/or social problems which
cruitment of personnel and their training on the principles of both dia- may negatively impact quality of life and complicate self-care, particularly where
betes education and behavior change strategies. The staff must develop diabetes outcomes are sub-optimal.
patient-centered and structured education programs for people with • Refer to mental health specialist advice according to local availability of such
professionals.
diabetes.
• Educational strategies and materials aligned with the needs of people
with diabetes with due consideration of the socio-cultural factors are Background
necessary. Institutional support is critically important at the practice, Complex environmental, social, behavioral, and emotional factors, to-
community, and health care system levels [Figure19]. gether known as psychosocial factors, play a crucial role in optimum
diabetes management and achieving satisfactory medical outcomes. The
daily demands of the disease course and management interrupts the psy-
PSYCHOSOCIAL ISSUES chological well-being of people with diabetes. The prevalence of comor-
bid psychosocial problems is greater in patients with diabetes than in the
Recommendations general population.[941] The psychological and social issues such as
stress, anxiety, depression, eating disorders, cognitive dysfunction, or
Recommended Care other psychological disorders are associated with poor self-care, increased
mortality, functional impairment, increased healthcare cost, loss of pro-
Approach to care
• Diabetes management should be carried out within a framework of informed and
ductivity, and reduced quality of life.1131–1134 Patient’s psychosocial con-
shared decision-making, following the philosophy of responsible patient- ditions have significant impact on the overall outcomes of diabetic care
centered care. process.1135–1137
• Psychosocial care should be provided to all individuals with T2DM using a Euthymia is a target, as well as a tool, for diabetes management. 1138,1139
collaborative, patient-centered care approach with referral to mental health care Psychosocial well-being comprehends both physical and mental health,
professionals where needed.
• Family members and other close ones in the management of diabetes must be
and is integral to diabetes- care and self-management. The ADA and the
involved American Association of Diabetes Educators (AADE) have focused on
• Self-disclosure of diabetes, as opposed to maintenance of confidentiality, the role of diabetes self-management education and support (DSMES) on
should be decided on a case-to-case basis, keeping the sociocultural improving psychosocial benefits, including the reduction of depression.
environment in mind 1140–1142
In addition, integrating mental health services in diabetes man-
• HCPs should take care of their own psychosocial health,
• Physicians should consider screening tools for diagnosis of diabetes-related agement can help with effective coping strategies. Yoga, or any kind of
anxiety: Hamilton Rating Scale for Depression and Hospital Anxiety and physical activity tailored for an individual patient can also help in the
Depression Scale (HADS), Generalized Anxiety Disorder-7 Scale, Symptom
Checklist-90, Diabetes Distress Scale, Diabetes Quality of Life Questionnaire,
management and balancing the mental health by improving glycemic
Hypoglycemia Fear Survey and Diabetes Fear of Injection and Self-Testing control, anxiety, depression, and QOL as well as exercise self-efficacy
Questionnaire (ESE).
• A careful assessment of depression: use of structured clinical interviews and self-
reported measures such as the Beck Depression Inventory, Centers for The IDF 2018 guideline has suggested the inclusion of a mental health
Epidemiologic Studies Depression Scale, PHQ-9, and HADS. The Geriatric professional in the multidisciplinary team and highlighted the need for
Depression Scale is used to screen for depressive symptoms in older individuals.
• Eating disorders, sexual dysfunction and substance abuse must be screened in patients
counselling a patient in the setting of on-going diabetes education and
at risk care.1143The AAACE has recommended, cultural and faith-based aspects
• Physicians should asses the socioeconomic status and education profile of the patient of therapy during counselling.254
while planning therapy. In India, heterogeneity in linguistic, cultural, religious, socioeconomic,
• Interview of patient’s spouse/parent/children (offline or online) for better assessment educational, regional, and familial factors affects the clinical progression,
of patient’s psychosocial aspect in Diabetes Mellitus.
• Listening to a patient can be a good way to look into this aspect. But time is the most
treatment and outcome of diabetes management. While family and com-
concerning part. So recorded audio / video of patients can be sent to HCP and within munity support medically-impaired persons as a part of our ethos, societal
a stipulated time he can revert back to the patient. insensitivity often exhibits itself, as culinary cruelty in many ways for
Specific interventions:
example: Indian patients with T2DM showed a significantly higher per-
• The psychosocial needs of specific groups, e. g., children, adolescents, and youth of ception of burden of social and personal distress associated with the
marriageable age, adults of reproductive age group, antenatal women, the elderly, the disease, and have been reported to have one of the lowest levels of psy-
marginalized, and members of ethnic/religious minorities must be kept in mind. chological well-being based on the World Health Organization-5 (WHO-
• Coping skills training to prevent and manage diabetes distress should be an 5) Well- being Index.1141,1144 These challenges and strengths warrant the
integral part of diabetes management. Individuals should be taught to integrate
positive coping skills and unlearn negative coping.
development of India-specific recommendations for psychosocial man-
• Nonpharmacological psychological therapy such as behavioral therapy and cognitive agement of diabetes, sensitive to and appropriate for, the Indian con-
behavioral therapy must be offered when appropriate. text.1145
• People with hypoglycemia unawareness should be warned of this problem and the
treating physician should relax tight glycemic control in order to restore
Considerations
hypoglycemia awareness.
• Gluco-vigilance must be maintained while prescribing psychotropic drugs that are Diabetes care and self-management is likely to be affected in presence of
known to influence carbohydrate metabolism. a mental health disorder that notifies patient’s psychosocial condition.
• The use of CGM can help to allay the fear of hypoglycemia and help in the Detection of such disorders in relatively brief consultations with diabetes
improvement of psychosocial well being professionals is challenging. There is a need for some basic training to
• Personalized self-management support programs and the use of social media in
patient education, and e-health-based psychological interventions are useful.
diabetes professionals in management of psychosocial issues, and for
• Digital mental health intervention in the form of the peer support element, diabetes- appropriate referral approach to mental health professionals with a knowl-
relevant content and examples, and check-in on their mental health and diabetes edge of diabetes, especially for seriously affected patients.
self-management regularly can ease the overall implementation.
• Group home telemedicine for young adults with T1D will positively affect diabetes
distress, self-efficacy, and diabetes-specific communication
• Use of cognitive behavioral therapy help in addressing psychosocial issues.
TYPE 2 DIABETES MELLITUS IN YOUNG AND

ADOLESCENTS
Recommendations
Recommended Care
• Risk-based screening for prediabetes and/or T2DM should be considered in

asymptomatic children and adolescents, performed after puberty or after ten years of
age, whichever occurs earlier.
- If tests are normal, repeat testing at a minimum of 3-year intervals or more
frequently if BMI increases.
• Fasting plasma glucose, 2-h plasma glucose during a 75-g oral glucose tolerance
test, and HbA1c can be used to test for prediabetes or diabetes in children and
adolescents.
- Panel of pancreatic autoantibodies should be tested to exclude the possibility of
autoimmune T1DM.
- The patient should be evaluated for monogenic forms of diabetes or pancreatic diabetes if
clinically indicated 1156.
• Treatment of youth-onset T2DM should include lifestyle management (long-
term weight management, vigorous physical activity, healthy eating patterns),
Figure 20: Indications to consider for referral to mental health profes- diabetes self-management education, self-monitoring of blood glucose, and
pharmacologic treatment.
sional • A family-centered approach to nutrition and lifestyle modification is essential,
and nutrition recommendations should be culturally appropriate and sensitive to
family resources.
Rational And Evidence • Bariatric surgery may be considered in adolescents with marked obesity (BMI:
Challenge >35 kg/m2 or 120% of 95th percentile)1157 and uncontrolled glycemia and/or
severe comorbidities despite lifestyle and pharmacologic intervention.
• Blood pressure should be measured and optimized to reduce risk and/or slow the
• Diabetes depression and anxiety have bidirectional impact on each progression of diabetic kidney disease.
other. Being diagnosed with diabetes imposes a life-long psychological • Youth with T2DM should be screened for the symptoms of other comorbidities,
including laboratory studies when indicated for neuropathy, retinopathy, non-
burden on the patient and his/her family. Prevalence of clinically sig- alcoholic fatty liver disease, obstructive sleep apnoea, and polycystic ovary syndrome
nificant depression, anxiety, and eating behavior disorder are consider- (in female adolescents), cardiovascular disease, and dyslipidemia.
ably more common in patients with diabetes than in those without the • Starting at puberty, preconception counseling should be incorporated into routine
diabetes clinic visits for all females of childbearing potential.
disease.1146–1148 • Patients should be screened for smoking and alcohol at diagnosis and regularly
• The findings from a systematic review and meta-analysis conducted on thereafter.
248 observational studies demonstrated that almost one in four adults
with T2DM experienced depression; while depression was more com-
Background
mon in patients with <65 years of age compared with elderly. 1149
Until recently, most children and adolescents with diabetes had type 1 diabetes
• Poor psychological functioning can seriously interfere with daily diabe-
(T1DM). However, the prevalence of T2DM in children and adolescents is
tes self-management, with subsequent poor medical outcomes and high
dramatically increasing1158. The onset of diabetes at a younger age is associ-
costs. 1150,1151
ated with more prolonged disease exposure and increased risk for chronic
• Solution
complications. Young-onset T2DM essentially affects working-age individ-
• Collaborative care interventions and a team approach for diabetes man-
uals, further accentuating the adverse social effects of the disease. Asian
agement have demonstrated efficacy in self-management with improved
Indians tend to develop T2DM at a younger age than white
psychosocial outcomes. 1152,1153
Caucasians1159,1160; additionally, there has recently been a downward shift
• A systematic review and meta-analysis have shown that, overall, psy-
in the age (<30 years) at the onset of T2DM in India1161–1166. As in adults,
chological interventions are effective in improving glycemic control in
the major predisposing diabetes risk factors in children and young adults
T2DM. 259
include obesity, decreased physical activity, family history, and a sedentary
• A randomized-controlled study showed that web-based guided self-help
lifestyle. In addition, other factors, including prenatal factors (e. g., low birth
centered on cognitive behavior therapy for people with diabetes with
weight, maternal under-nutrition), the biological propensity to central obesity
mild-to-moderately severe depression is effective.1154
and insulin resistance, low lean mass, diabetes during pregnancy, impaired
• Psychological counseling can contribute to improved adherence and
glucose tolerance, and urban stress are associated with a high prevalence of
psychological outcomes in people with diabetes [Figure].1155
T2DM in Indian children and young adults.1167–1175
Data on the prevalence of young onset T2DM are scarce worldwide, especially
Implementation
in India1176. It has been estimated that 1 in 3 new cases of diabetes mellitus in
• Major component of implementing these recommendations is the in-
the USA diagnosed in youth younger than 18 years is T2DM and is more
volvement of HCPs and their training on principles of both diabetes
common among youth between 10 and 19 years of age1158. A comparison of
education and psychosocial interventions.
Indian and Western diabetes registries suggests that young-onset T2DM is less
• HCPs are required to develop a collaborative, patient-centered medical
common in Asian Indians than Caucasians. As per the Indian Council of
care strategy for all patients with diabetes to improve health outcomes
Medical Research- Young Diabetes Registry (ICMR-YDR), 22.8% of youth
and quality of life.
with diabetes had a diagnosis of T2DM, compared to 70.6% with T1DM1177.
• HCPs must be trained in applying psychological assessment tools and
Data from southern India suggest an incidence rate for T2D of 20.2 per 1000
monitoring procedures, for diagnosis and periodic evaluation.
person-years among adolescents with standard glucose tolerance, followed up
• Collaboration with mental health specialists who have knowledge in
for a median of 7.1 years1178. A recent analysis of the Comprehensive National
diabetes can help extend the education and training of other mental
Nutrition Survey (CNNS) showed that among adolescents aged 10-19 years
health specialists in relation to diabetes.
screened using HbA1c, the prevalence of dysglycemia (diabetes/prediabetes)
was 12.3% and 8.4% among boys and girls, respectively1179.
Pathophysiology of type 2 diabetes mellitus in young versus adults

The mechanisms of development of T2DM in young people are similar to
those in older patients; however, the speed of onset, severity, and interplay of
reduced insulin sensitivity and defective insulin secretion might differ in pa- on the use of these agents in this population. 1196 Bariatric surgery has
tients who develop the disease at a younger age1180. Studies suggest that loss emerged as a viable treatment option in young individuals with T2DM, and
of β-cell function plays a significant role in the development of T2DM in evidence has shown that it is safe and effective in obese adolescents.
youth1181,1182, and that the decline in β-cell function is accelerated in young- However, clinical data to support this are limited, and the procedure should
onset T2DM compared to older onset T2DM (20–35% per year compared to be considered only after puberty and the attainment of skeletal maturity.
7%)1183. It has also been suggested that T2DM in adolescents and children
might have a more aggressive course compared with adult later onset HYPERGLYCEMIA IN PREGNANCY - PRE GDM & GDM
T2DM1180. They also seem to run a higher risk of micro- and macrovascular Recommendations
complications compared to older onset T2DM or even T1DM adjusted for the
duration of diabetes 1184–1187. Recommended Care
Screening and diagnosis PRECONCEPTION CARE:

The diagnostic criteria for diabetes in children and adolescents are similar Preconception care and planning should be introduced in all women with diabetes or a
history of Gestational Diabetes before planning pregnancy.
to those in adults and include:
Educate about the risks of unplanned pregnancy, its consequences, and the importance of
Symptoms of diabetes mellitus such as polydipsia, polyuria, and unex- achieving strict preconception glycemic control (HbA1c≤ 6.5%) to minimize these adverse
plained weight loss plus casual glucose concentration≥200 mg/dL (11.1 maternofetal outcomes.
mmol/L) in venous plasma, fasting glucose ≥126 mg/dL (7.0 mmol/L) in Counsel on contraceptives and family planning in all women with diabetes in the
venous or capillary plasma, or 2-h glucose during OGTT ≥200 mg/dL reproductive age group.
Insulin is the first line of therapy to treat hyperglycemia in pregnant women with pre-existing
(11.1 mmol/L) in venous plasma or capillary whole blood or HbA1c diabetes as it does not cross the placenta
≥6.5%1188. Children at substantial risk for the presence or the develop- General assessment of overall health, including a comprehensive assessment of metabolic
ment of T2DM should be tested. Children and adolescents who are over- status and screening for complications and comorbidities of diabetes: Screen for
weight or obese (BMI >90th percentile) and have a family history of microvascular complications, including retinopathy and nephropathy, and assess
cardiovascular health, especially in women with longstanding diabetes and high
T2DM in first-or second-degree relatives must be screened. Children with
cardiovascular risk.
signs of insulin resistance or conditions associated with insulin resistance Review all concomitant medications for their appropriateness during pregnancy. Educate
such as acanthosis nigricans, hypertension, dyslipidemia, and polycystic about the teratogenic effects of ACEi, ARBs, and statins and the need to stop their
ovarian syndrome, must also be screened regularly.1189 preconceptions and switch to safer drug options.
As the etiology of diabetes in young Asian Indians is heterogenous1190, A dose of 400 μg/day of folic acid starting at preconception and continued till 12 weeks of
pregnancy should be recommended to avoid neural tube defects.
the following clinical presentations should alert the clinician to the pos-
Comprehensive nutritional and lifestyle assessment, advice, and weight loss assistance
sibility of other forms of non-type two diabetes in youth. should be provided.
• Suspect T1DM in youth, family history of diabetes, absence of obesity
or signs of insulin resistance, and presentation with severe hyperglyce- Antepartum care:
mia with or without ketosis. The presence of pancreatic autoantibodies
and lack of endogenous insulin reserve by C-peptide assay (whenever
available) will help in making the diagnosis. During the first 10 weeks of pregnancy, offer retinal and renal assessment if not evaluated
preconception.
• Suspect pancreatic diabetes (fibro calculous pancreatic diabetes-FCPD) Aim for tight glycemic control with HbA1C 6%, FBS 70-90 mg/dl & 2 hr. PPBS 100-120
in lean youth with features of exocrine pancreatic insufficiency and mg/dl if these can be achieved without significant hypoglycemia in women with pre-
presentation with severe non-ketosis prone diabetes. Imaging studies gestational diabetes on intensive insulin therapy.
(plain X-ray or ultrasound of the abdomen) will reveal evidence of Insulin is the first-line treatment recommended in all pregnant women with pre-GDM. Basal
chronic pancreatitis (calculi or duct dilatation). bolus therapy is most effective in helping achieve these tight glycemic targets.
All human insulins (Regular/NPH) are safe in pregnancy.
• Suspect monogenic forms of diabetes (such as maturity-onset diabetes Insulin Aspart and Lispro are approved for use in pregnancy although we have insufficient
of the young-MODY) in youth with a positive family history of diabetes data on glulisine. Insulin detemir has been approved for use in pregnancy, glargine use has
across three generations, absence of signs of insulin resistance, and non- been found safe in pregnancy, and Degludec is still not supported for use in pregnancy.
ketosis prone diabetes. Genetic studies are needed for confirmation of Offer ultrasound monitoring as per protocol to monitor fetal growth and timely detection of
the diagnosis. any structural abnormalities.
Low-dose aspirin 100–150 mg/day starting at 12 to 16 weeks of gestation may be prescribed
to lower the risk of preeclampsia.
Management of type 2 diabetes mellitus in children and adolescents
The ideal treatment goal is normalizing blood glucose values and HbA1c. Intrapartum care:
Weight control is essential for reaching treatment goals and effectively Diabetes is not an indication of preterm or cesarean delivery. Pregnancy may be continued to
treating T2DM in adolescents. Although lifestyle modification is the most term if maternal metabolic parameters are satisfactory and there are no indications of adverse
commonly used intervention in adolescents with T2DM, less than 20% fetal growth or complications.
Capillary blood glucose should be within the optimum level of 70-110 mg/dL during labor.
achieve or maintain adequate glycaemic control with lifestyle intervention Appropriate dose of regular insulin with dextrose infusion must be preferred to achieve target
alone1191. Aerobic activity, combined with diet, can reduce systolic blood glycemic levels during labor.
pressure, lower total cholesterol, raise HDL cholesterol, and improve endo- Refer to RSSDI recommendations on inpatient hyperglycemia management for detailed
thelial function in overweight children with T2DM1192. Metformin is the most insulin management protocol during labor.
appropriate starting point for pharmacological treatment in children with
Postpartum care:
T2DM. However, results of the TODAY study suggest that monotherapy
Monitor blood glucose levels and consider insulin dose reduction to avoid hypoglycemia in
with metformin was associated with durable glycaemic control in only 50% women with pre-GDM.
of children and adolescents1192,1193. Insulin therapy is indicated in children Most women with GDM may return to normoglycemia, and insulin may be stopped post-
with severe osmotic symptoms or marked hyperglycemia with or without delivery.
ketosis1194. Data from the ICMR-YDR indicate a significant proportion of Change glycemic targets to non-pregnant targets as per standard recommendations.
youth with T2DM in India were on insulin. 1177 However, the combination of Reassessment of glycemic status at 6-12 weeks postpartum with a 75 gm OGTT in women
with GDM. Educate them on the risk of progression to Prediabetes or eventually T2DM and
metformin and insulin has not been shown to improve the durability of strategies to prevent it.
glycemic response or promote β-cell 1195 preservation in youth with Recommend breastfeeding
T2DM. While there has been some recent evidence supporting the use of Reminder about the importance of contraception and pre-conception care and planning for
glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, exenatide pregnancies in the future.
LAR, and dulaglutide) in youth with T2DM there are no data from India
Background complications, such as hypertension, uteroplacental insufficiency, and

1. Gestational Diabetes and PreGDM iatrogenic preterm birth because of worsening renal function.1213
The prevalence of Hyperglycemia in pregnancy is increasing. It includes Hypertension, especially in the presence of nephropathy, increases the
Gestational Diabetes Mellitus (GDM) and Pregestational Diabetes risk of preeclampsia, uteroplacental insufficiency, and stillbirth.1214
Mellitus (PreGDM), which consists of all forms of pre-existing diabetes, Self-monitoring of fasting and postprandial blood glucose should be done,
i.e., Type 2, Type 1 diabetes, and even MODYs. while pregestational diabetes pre-prandial monitoring can be considered.
Conventionally any degree of hyperglycemia detected first time in preg- Lower SMBG limits are based on normal pregnancy values. HbA1c may
nancy is called GDM. Still, most global organizations term dysglycemia be helpful as a secondary measure of glucose control in pregnancy but
saw the first time in pregnancy in the first trimester (early pregnancy) as secondary to SMBG. HbA1c targets are lower in pregnancy due to increased
pre-existing diabetes in pregnancy. True GDM is diabetes detected for the red cell turnover, ideally below 6%, relaxed to -7% if there is frequent
first time in the second or third trimester of pregnancy which is clearly not hypoglycemia, and requires more frequent monthly monitoring.
overt diabetes.923 Pre-gestational diabetes is a risk factor for acute myocardial infarction
However, the prevalence of undiagnosed diabetes, as well as prediabetes, during pregnancy. Pregnancy may be contraindicated in patients with pre-
is increasing in India. SE Asians have an 11-fold increased risk of devel- existing coronary artery disease due to the hemodynamic changes that
oping GDM than Caucasians. Therefore DIPSI recommends universal may occur during pregnancy, causing myocardial infarction and
screening of all pregnant women for GDM at the first point of contact death.1215 Recalcitrant nausea and vomiting due to gastroparesis result
to detect any early GDM to avoid adverse gestational programming of the from diabetic neuropathy in pregnant women. Gastroparesis impacts the
fetus1197,1198 as well as to prevent early pregnancy complications.1197 The interaction between diet and diabetes regimens and complicates
DIPSI guidelines endorsed by the IDF, WHO, and FIGO define any glycaemic control, thereby increasing the risk of hypoglycaemic epi-
manifestation of hyperglycemia in pregnancy as GDM as it represents sodes.1216 Diabetic ketoacidosis is a life-threatening emergency observed
the detection of chronic β cell dysfunction and is therefore considered a in 5–10% of all pregnancies complicated by pre-gestational diabetes.
stage in the evolution of Type 2 DM. 1199,1200 Common clinical presentations include abdominal pain, nausea and
Pre-existing uncontrolled diabetes in women before conception can lead vomiting, and altered sensorium. Hypoglycemia and Hypokalemia are
to severe congenital disabilities, spontaneous abortions, and adverse preg- frequent complications of diabetic ketoacidosis management. Hence, glu-
nancy outcomes.1201 The overall prevalence of pre-gestational diabetes cose and potassium concentrations should be monitored closely.1217,1218
has been recorded to be doubled from 1999-2005.1202 Recent studies
have revealed that the prevalence of pre-existing diabetes in pregnant Table 40: Checklist for preconception care for women with
women is 3.4%-3.8%, most of whom were suffering from diabetes 1211
T2DM.1203,1204 Gestational diabetes can have deleterious effects on preg-
nancy, leading to maternal, fetal, and perinatal complications. The com-
plications include still-birth, spontaneous abortion, pre-eclampsia, peri-
natal mortality, low birth weight, respiratory distress, neonatal death,
neonatal hypoglycemia, etc. 1205–1207
2. Screening criteria (Where, when, and How)

DIPSI recommends a non-fasting Oral Glucose Tolerance Test (OGTT)
with 75g of glucose with a cut-off of ≥ 140 mg/dl after 2 hours, whereas
WHO (1999) recommends a fasting OGTT after 75g glucose with cut-off
plasma glucose of ≥ 140 mg/dl after 2-hour. 1208,1209 1210,1211
3. Screening and management for diabetes complications

Early screening of diabetes complications like retinopathy, neuropathy,
heart failure, and chronic kidney disease in the pre-conception period is
essential as they can be life-threatening and associated with lower quality
of life for both the mother and the fetus if not diagnosed or treated at an
early stage. Poorly controlled pre-gestational diabetes may lead to end-
organ severe damage that may result in life-threatening conditions. These
complications can be controlled or prevented with appropriate diabetes
management.1212 Diabetic retinopathy is the leading cause of blindness,
and there can be a worsening of retinopathy during pregnancy. Women
with diabetes who become pregnant should have a comprehensive eye
examination before pregnancy or as soon as pregnancy is confirmed in
the first trimester. They should be monitored closely throughout pregnan-
cy, at the first visit, if not assessed within the previous six months, then
once in each trimester. Diabetic nephropathy is estimated to be present in
5–10% of diabetic pregnancies, and progression to end-stage renal dis-
ease has been reported in several women. Also, women with pre-existing
diabetic nephropathy are at significantly higher risk for obstetric
peaks between 28 and 32 weeks of gestation.1216 Insulin pump therapy

is also considered beneficial in maintaining target glycemic control in
pregnant women with pre-gestational diabetes without any increase in
the risk of hypoglycemia. However, the cost of therapy and the risk for
marked hyperglycemia or DKA due to insulin delivery failure from inad-
vertent mechanical error could be an issue.1219
Women with pre-existing diabetes are at a high risk of preeclampsia.
Hence the American College of Obstetricians and Gynecologists recom-
mends the use of low-dose aspirin (81 mg/day) prophylaxis to be initiated
between 12 weeks and 28 weeks of gestation (ideally before 16 weeks of
gestation) and continued until delivery.1216
5. Optimization of anti-hypertensive medications [Table 31]
Use of ACE inhibitors and angiotensin receptor blockers (ARBs) as an-
tihypertensive agents are contraindicated in women with pre-existing di-
abetes and planning pregnancy as these medications are teratogenic and
can cause intra-uterine growth retardation, fetal renal dysplasia, and oli-
gohydramnios.1212,1220–1222 A large randomized controlled trial in preg-
nant women with pre-existing or gestational hypertension showed that
targeting a diastolic blood pressure (BP) of 85 mmHg vs. 100 mmHg
reduced neonatal respiratory complications and rates of severe maternal
hypertension (i.e., >160/110 mmHg).1223 Labetalol, methyldopa, diltia-
zem, nifedipine, clonidine, and prazosin are safe anti-hypertensives dur-
ing pregnancy. Use of atenolol is not recommended in pregnancy.
Chronic diuretics are also not recommended as they are associated with
restriction of maternal plasma volume that leads to a reduction in
uteroplacental perfusion.1220 Severe preeclampsia and acute hypertension
management may be treated with vasodilators like hydralazine during
pregnancy.
6. Management of dyslipidemia
Dyslipidaemia identified during pregnancy should be treated with diet
4. Optimization of antidiabetic regimes and exercise intervention and glycemic control if indicated. A lipid profile
No OADs are approved for pre-existing diabetes in pregnancy, although at preconception in women with Familial Hypercholesterolemia (FH)
glyburide and metformin have been used in multiple RCTs for GDM. must be conducted and a target level of LDL cholesterol, HDL cholester-
Minimal data on thiazolidinediones or metiglinides and no data on ol, and triglycerides as <100 mg/dL (2.6 mmol/L), >35 mg/dL (0.905
incretin-based DPP-4 inhibitors and GLP-1 analogues are available.1219 mmol/L) and <105 mg/dL (1.7 mmol/L), respectively must be estab-
However, none of these are found safe and are hence not recommended in lished.1224 The use of statins is contraindicated during pregnancy due to
pregnancy. Metformin and glyburide have been used during pregnancy, teratogenicity.
but these drugs cross the placental barrier and should be replaced with
insulin therapy at the earliest.1212,1219,1220 Recent data on glyburide has Preconception planning and care [Table 41]
raised safety concerns, including an increased risk of neonatal hypogly- Before conception, a set of treatment regimens that aim to optimize social,
cemia. Potential problems for SGLT2 inhibitors in pregnancy due to metabolic, and psychological aspects in a woman with pre-gestational
profound polyuria in a pregnant patient with familial renal glycosuria diabetes (T1DM and T2DM) or a history of GDM in previous pregnancy
have been reported. Since pregnancy causes polyuria and glycosuria gen- is referred to as pre-conception management.1220 minimize pregnancy
erally due to increased glomerular filtration rate, SGLT2- inhibitors are complications and congenital malformations, it is essential to introduce
not expected to be beneficial and are not recommended.1219 Metformin preconception care in the primary care plan for all women with childbear-
has also been associated with prematurity, and long-term follow-up in ing potential.1225
metformin is still awaited. MITY Study showed SGA in infants exposed Early diagnosis, optimized glycemic control, proper nutrition, lifestyle
to metformin intrauterine. Further studies have shown increased visceral modification, and regular follow-up can help in successful pregnancy in
adiposity, increased head circumference, and subscapular skin fold thick- people with diabetes. The introduction of multidisciplinary clinics in
ness, and further increased adiposity and weight gain in children exposed managing pregnancy with diabetes can reduce the rate of adverse mater-
to metformin during pregnancy. nal outcomes and perinatal mortality and improve neonatal care.1226
Insulin does not cross the placenta and is the first choice to attain the
target glycaemic goal in pregnant women with pre-existing diabe- Counseling
tes.1220,1221 Basal bolus regimen is ideal in diabetes with pregnancy. The pre-conception counseling process should be discrete, concise, and
Considering alterations in the physiology of pregnant women, daily considerate and must provide a clear explanation with sensitivity to social
SMBG is required more frequently, and insulin doses must be optimized and cultural conventions. Women with pre-existing diabetes should be
at different stages of pregnancy as per requirement.1221 Insulin require- counseled about the need for contraception till target glycemic control is
ments may increase as the pregnancy progresses, and the requirement achieved before going ahead with the planned pregnancy.
Table 41: Elements of a preconception plan Table 42: Glycemic target in women with pre-existing Type 2 diabe-
tes mellitus before and during pregnancy
Counseling Assessment of Glycemic Supportive investigation
medication control and management Condition Glycemic target
Need for contraception Potentially Risk of Optimum HbA1c level

Fasting 70-95 mg/dL (3.9-5.3 mmol/L)
and effective teratogenic drugs hypoglycemia Urine albumin: Creatinine
measures Use of oral Risk of maternal ratio 1-h postprandial 110-140 mg/dL (6.1-7.8 mmol/L)
The risk associated with hypoglycaemic and fetal Lipids
unplanned pregnancy agents complications
Test for HIV, HBV, HCV, 2-h postprandial 100-120 mg/dL (5.6-6.7 mmol/L)
Financial/family Insulin therapy due to VDRL, pap smear, rubella,
planning Use of insulin hyperglycemia
Need for strict analogs Educate on self- TSH, and fundus
glycaemic control and monitoring of Cardiac evaluation Table 43: Safety of medicines for diabetes before and during
insulin BG pregnancy
Noninsulin glucose-lowering agents

HbA1c: Glycosylated Hemoglobin, BG: Blood Glucose, HIV: Human Immunodeficiency
Virus, HBV: Hepatitis B Virus, HCV: Hepatitis C Virus,
TSH: Thyroid Stimulating Hormone Compound Effects on pregnancy
Class
Patients must be counseled and prescribed appropriate contracep- SU Glimepiride Intrauterine death, skeletal deformities, and fetal growth
tive measures until the metabolic parameters are relevant to con- retardation.
ceive. Since the primary goal for glycemic management in the
Glipizide Crosses placental barrier
preconception period and during the first trimester is to obtain
the lowest HbA1c levels possible without hypoglycemia, women Glibenclamide It may cross the placental barrier and increases neonatal
should be made aware that they can have a planned conception hypoglycemia. Long-term safety data in offspring of
mothers exposed to glibenclamide is not available.
only with HbA1c, preferably less than 6.5% to lower the risk of
congenital anomalies.1220,1226 Critical complications with T2DM, Biguanide Metformin Crosses placental barrier and shows congenital
such as hypertension, intrauterine growth retardation, and risk of malformation; however, lower in rate than those not on
metformin medication; increased risk of prematurity.
obesity, along with their preventions and management, should be
explained to the patients during pre-conception counseling.1220 α-glucosidase Acarbose
Pregnant women with pre-existing diabetes must be advised to inhibitors
avoid fasting. However, religious fasting is a personal decision, Meglitinides Nateglinide Transfusion through the placental barrier is unknown yet.
and a practical approach should be explained with emphasis on Repaglinide May produce a risk of developmental toxicity in the fetus
the risks to the mother and the fetus.1227 Pre-conception counsel- at a lower risk.
ing must minimize the risk of pregnancy complications in girls TZDs Pioglitazone Crosses placenta, delayed fetal development, reduced fetal
and women in their reproductive age with diabetes. Such counsel- weight, and post-implantation losses.
ing can improve the mother’s health and reduce cost burdens for Rosiglitazone Crosses placenta, causes fetal growth retardation, fetal
the mother and the child.1221 death, and placental toxicity.
Insulins
Glycemic target-preconception and antepartum
It is recommended that women with T2DM who are planning Rapid-acting Aspart, Lispro, Insulin Aspart is known to be most effective in managing
pregnancy should be switched from oral or noninsulin injectable analog and Gluisine, glycemic control without causing the risk of hypoglycemia
during preconception and throughout pregnancy.
hypoglycemic agents to insulin before conception, if possible. The
Lispro was found to be safe and effective in maintaining
primary goal of women with pre-gestational diabetes is to main- BG levels.
tain optimal glycemic levels. Effective measures must be taken to No safety and efficacy data are available on the use of
maintain the ideal glycemic value while minimizing the risk of glargine and glulisine in pregnancy.
hypoglycemia. The IDF recommends a pre-conception HbA1c lev- Determire is safe in pregnancy with an ample amount of
el of <7%, whereas ADA and National Institute for Health and data supporting it.1228
Degludec insulin in pregnancy has no data currently for its
Clinical Excellence (NICE) recommend an HbA1c level lower use in pregnancy.
than <6.5%, provided it is safely achieved. 1212 To prevent Though there is no RCT available for the use of Glargine in
chances of spontaneous abortions and major congenital pregnancy, based on safety data, it is recommended that if
malformations, target HbA1c must be as close to normal as pos- the patient is already on glargine insulin and if the treating
sible without significant hypoglycemia.1215 HbA1c should be clinician feels that withdrawing glargine may deteriorate
the glycemic control, then on clinician’s discretion,
assessed monthly due to the changing kinetics of RBCs and phys- glargine may be continued in pregnancy. Detemir is safe in
iological alterations in glycemic aspects in pregnancy.1220,1221 The pregnancy and is recommended for its use. The safety of
ADA recommends HbA1c testing during fasting, SMBG monitor- degludec has been shown in a recent publication in
Type1DM. Still, it is yet to be recommended for use in
ing, and pre-prandial and postprandial in pregnant women with
pregnancy by any global organization or drug authority.1228
diabetes.1221 In women with pre-existing diabetes, provision of
basal and prandial insulin needs with intensified insulin regimens TZDs: Thiazolidinediones, BG:
Blood glucose
(multiple-dose regimens of subcutaneous long-and short-acting in-
sulins) are known to give the best results. Rapid-acting insulin
analogues, as a part of a basal-bolus regime or via an insulin Antepartum care
pump, give better postprandial control. Pre-prandial monitoring Folic acid supplementation
can help in dose adjustment of insulin regime and insulin pump. Periconceptional folic acid supplementation decreases the occurrence and
Monitoring of postprandial blood glucose aids in lowering the risk recurrence of neural tube defects (NTDs). Hence, in preconception
of preeclampsia and macrosomia. counseling, patients should
Table 44: Safety of medicines for complications of diabetes before maternal or fetal complications, elective birth before 37 weeks for women
and during pregnancy with type 1 or 2 diabetes must be considered.1212 Studies have suggested
that the blood glucose target should be maintained at 100-126 mg/dL to
Class Compound Effects on pregnancy prevent hypoglycemia in neonates. It was found that neonatal hypergly-
cemia is at higher risk when the maternal blood glucose level reaches
ACEIs Lisinopril, Perindropril, Usage of ACEI and ARBs to treat hypertension >180 mg/dL. In a retrospective analysis including 137 singleton cases,
Enalapril, Moexipril, should be avoided during pregnancy as they
Trandolapril and Quinapril severely affect the control over renal function and
mothers with a blood glucose level of about 72-144 mg/dL (4-8 mmol/L)
also fetal and neonatal BP. They may also cause resulted in 87% (n=26) neonatal hypoglycemia, of which 13 neonates
ARBs Losartan, Telmisartan oligohydramnios and skull defects. were admitted to ICU. These 13 neonates were born with maternal blood
Statins Atorvastatin, Rosuvastatin, Usage of statins in the reduction of elevated levels
glucose levels >144 mg/dL (8 mmol/L). Thus, blood glucose must be
Fluvastatin of cholesterol should be avoided in pregnancy as monitored closely and controlled within the targets.1232 The capillary
well as in lactation as they may cause congenital plasma glucose must be monitored every hour during labor and birth in
malformation. women with diabetes and ensured that it is maintained between 70-110
Lipase Orlistat Obesity treatment in pregnancy with orlistat shows mg/dL (3.9-6.1 mmol/L) in women with pre-existing T2DM.1212
inhibitor a low risk to the fetus and should be used Monitoring should be carried out 2-h to 4-h during the latent stage; the
cautiously during pregnancy.
active stage requires monitoring every 1-2 h and every hour in patients on
ACEIs: Angiotensin Converting Enzymes, ARBs: Angiotensin Receptor Blockers, BP: Blood glucose infusion. During labor, women with pre-gestational diabetes gen-
Pressure erally should undergo continuous intrapartum electronic fetal monitor-
ing.1216 To achieve target glycemic levels, IV dextrose and insulin infu-
sion during labor and birth may be considered for women with diabetes
be educated on the folic acid requirement.1229 Women with pre-existing
whose capillary plasma glucose is not maintained between 70-110 mg/
diabetes who are planning to become pregnant must be advised to take
dL. Rapid-acting insulin analog like aspart or lispro are the preferred
folic acid (5 mg/day) until 12 weeks of gestation to reduce the risk of
choice in achieving the target glycemic value as they minimize the risk
having a baby with a neural tube defect.1212
of hypoglycemia.1221
Nutrition therapy and weight gain targets
Postpartum management
The primary aim of nutritional therapy in pregnancy is to provide calories
Care of newborn
for normal growth and development of the fetus while maintaining opti-
Neonates born to women with pre-existing T2DM are at a higher risk of
mized glycemic control and normalizing dyslipidemia. Due to physiologic
morbidities like macrosomia, hypoglycemia, respiratory distress, cardio-
changes that follow pregnancy, caloric requirements are increased during
myopathy, hematologic disorders, and hypocalcemia.1233 It is recom-
the second and third trimesters.1230 Wholesome food choices with 40–50%
mended to admit babies showing signs of the above morbidities to the
calories from complex, high-fiber carbohydrates, 15–30% calories from
NCU postpartum for proper care and management.1216 To minimize neo-
protein, and 20–35% calories from primarily unsaturated fats) are common-
natal complications, adequate control of diabetes in the antenatal period
ly advised.1216 To fulfill the additional dietary needs, diets are often altered
and newborn surveillance by a neonatologist are required.1220
or modified for the amount and type of carbohydrates consumed during
pregnancy. It is advisable to include a diet rich in omega-3 fatty acids and
Glycemic control
non-starch polysaccharides with a low glycemic index and avoid excess
Insulin requirement falls in the postpartum period by 34% more than in
intake of saturated fats and TFAs that can lead to an increased risk of
the preconception period. Over the next 1-2 weeks postpartum, insulin
complications. Legumes, unprocessed fruits, and vegetables should be in-
requirement returns to that required during the pre-conception period.
cluded in the diet. Vitamin D supplementation (10 μg/day) is prescribed for
Women on insulin should be closely monitored to avoid the risk of hy-
women at risk of vitamin D deficiency during pregnancy. Folic acid sup-
poglycemia during breastfeeding. Monitor maintenance of pre-feed cap-
plementation with a recommended dose of 400 μg/day is prescribed until
illary plasma glucose level of the neonate and assure it to be 40mg%
12 weeks of pregnancy to prevent the risk of neural tube defects. Vitamin A
supplementation, liver and liver products rich in vitamin A should be
Lactation
avoided as they may be teratogenic. Iron supplements are not often pre-
Breastfeeding should be encouraged in women with pre-existing diabetes.
scribed during pregnancy as they might be associated with unpleasant ma-
There is a sharp decline in the insulin requirement after delivery; hence,
ternal side effects. ADA suggests the Dietary Reference Intakes (DRI) be
the insulin dose needs to be adjusted accordingly.1220 Dietary care to
• >175 g of carbohydrate, >71 g of protein, and about 28 g of fiber in all
prevent the risk of obesity is of prime concern during lactation. Strict
pregnant women.1212,1215,1221,1231
blood glucose control for women with pre-existing diabetes who under-
went cesarean section is essential to avoid infection. Advise a snack
Weight management
before starting to breastfeed, especially to women on insulin, because
Obesity is a significant complication in women with pre-existing T2DM;
lactation is energy-intensive and can cause hypoglycemia in the mother
hence, weight management is essential to avoid CV risk in pregnancy.
if she feeds on an empty stomach. During lactation, women with pre-
ADA recommends that the weight gain of overweight women during preg-
existing diabetes can resume or continue to take metformin and insulin.
nancy should be 15–25 lb whereas, for obese women, it should be 10–20
ACE inhibitors, ARBs, oral hypoglycemics, obesity medicines, and
lb.1221 Maintenance of weight gain targets during pregnancy can be easily
statins should be avoided during breastfeeding.1212
done with the help of an appropriate dietary plan along with lifestyle inter-
ventions. Yoga, either individually or combined physical activity, has been
Postpartum contraception
remarkably helpful in weight management. Orlistat, a lipase inhibitor shows
One of the significant barriers to effective preconception care is un-
a low risk to fetal development; hence obesity/overweight in pregnancy can
planned pregnancy. To minimize the risk of congenital malformation
be treated with caution and close monitoring.
due to pre-existing diabetes and its complications, it is important to re-
mind women in the postpartum period about the use of effective contra-
Intrapartum care
ception and family planning. For women who do not choose permanent
Glycemic targets during labor and delivery
contraception with tubal ligation, long-acting reversible contraception
The timing and mode of birth must be discussed during antenatal appoint-
with an intrauterine device or implantable progestin are the most effective
ments, especially during the third trimester. If there are metabolic or other
forms of contraception and should be recommended.1234
DIABETES AND HYPERTENSION Background

Hypertension and Type 2 diabetes are commonly existing comorbidi-
RECOMMENDED CARE ties.1234 The prevalence of diabetes and hypertension in India is high
across all geographical settings and socioeconomic groups in middle and
• Measuring BP in diabetes patients
old age. The crude prevalence of diabetes and hypertension was 7.5%
- Major goals for the treatment of diabetes are to prevent or delay complications and optimize
the quality of life. The pathogenic relationship between T2D and hypertension is assumed to (95%CI, 7.3%-7.7%) and 25.3% (95%CI, 25.0%-25.6), respective-
be bidirectional. ly.1235 New-onset Diabetes Mellitus is 2.5 times in hypertension, 20 to
- Elevated BP levels are supposed to reflect at least partially the impact of the underlying
insulin resistance on the vasculature and kidneys, while there is clinical evidence suggesting
40% of IGT patients have HTN, 40 to 50% of Type 2 DM have hyper-
that disturbances in carbohydrate metabolism are more common in individuals with tension, and only 1/4 of HTN in DM is controlled. Cardiovascular risk in
hypertension. patients with both diabetes and hypertension is 3-fold.
- Ideal management of chronic conditions, such as T2D and hypertension, often includes
monitoring lifestyle changes and pharmacological interventions to improve metabolic
Individuals with high blood pressure often show insulin resistance and have a
health. higher risk of developing diabetes than normotensive individuals. It has been
- Home BP measurement has been recommended by many hypertension guidelines and observed that over the last 30 years, the prevalence of insulin resistance has
addresses several limitations of traditional office-based care, including reducing
misclassification because of white-coat or masked hypertension and an ability to take more increased significantly. Accordingly, hypertension and insulin resistance are
suitable action and a course of corrective therapy.1235 strongly related to an increased risk of impaired glucose tolerance, diabetes,
• Types of Hypertension: cardiovascular diseases, and endocrine disorders.1236 In addition, the major
- Systolic Hypertension cause of morbidity and mortality in diabetes is cardiovascular disease, which
- Non-Dipping Hypertension is exacerbated by hypertension. Both conditions are closely interlinked be-
- Nocturnal,
- B.P Variability cause of similar risk factors, such as endothelial dysfunction, vascular inflam-
• The recommended BP targets 1230 for individuals with diabetes should be <130/80 mm mation, arterial remodeling, atherosclerosis, dyslipidemia, and obesity. There
Hg and <140/80 in elderly patients. BP should be performed at every clinical visit.1231 is also substantial overlap in the cardiovascular complications of diabetes and
• Use of risk calculator1231 to estimate the 10-year risk of a first ASCVD event hypertension-related, primarily to microvascular and macrovascular disease.
(available online at tools.acc.org/ASCVD-Risk-Estimator-Plus) is recommended for
Common mechanisms, such as upregulation of the renin-angiotensin-
assessment of better stratify ASCVD risk and help guide therapy.
• First-line therapy for hypertensive individuals and individuals with urine albumin-to- aldosterone system, oxidative stress, inflammation, and immune system ac-
creatinine ratio $300 mg/g creatinine (A) or 30–299 mg/g creatinine (B). If one class is tivation, likely contribute to the close relationship between diabetes and
not tolerated, the other should be substituted. B should include a drug class hypertension.
- ACEI and ARB 1232
Various RCTs have been conducted in this field. ACCORD BP,
- CCB and/or thiazide-like diuretic
- The treatment should include a statin in primary prevention if LDL-C >70 mg/dL ADVANCE BP, Hypertension Optimal Treatment (HOT), and SPRINT
(1.8 mmol/L) (diabetes with target organ damage) or >100 mg/dL (2.6 mmol/L) examined the potential benefits of intensive versus standard blood pres-
sure control. However, the relevance of their results to people with dia-
betes is less clear. ADVANCE BP showed that the intervention reduced
(uncomplicated diabetes)
the risk of the primary composite end point of major macrovascular and
• Serum creatinine/estimated glomerular filtration rate and serum potassium levels should
be monitored. microvascular events (9%), death from any cause (14%), and death from
• Multiple drug therapy is often indicated in case of chronic kidney disease, CVD (18%). A 6-year observational follow-up found a reduction in risk
• The therapeutic strategy should include lifestyle changes, body weight control, and the of death in the intervention group attenuated but still significant.
effective treatment of the other risk factors to reduce the residual cardiovascular risk.
SPRINT trial1237 showed that the intensive systolic blood pressure target
• For individuals with hypertension and Chronic kidney disease, RAS inhibitors are first-
line drugs as they reduce albuminuria in addition to BP control. CCBs and diuretics lowered the risk of the primary composite outcome by 25% (MI, acute
(loop-diuretics if eGFR <30 ml/min/1.73m2) (160/100) can be added. coronary syndrome, stroke, heart failure, and death due to CVD), and the
• eGFR, microalbuminuria, and blood electrolytes should be monitored.1233 intensive target reduced the risk of death by 27%. Intensive therapy in-
• Patients with resistant hypertension who are not meeting blood pressure targets on
conventional drug therapy with three agents, including a diuretic, should be referred to a
creased the risks of electrolyte abnormalities and acute kidney injury.
certified hypertension specialist. Diabetic patients are believed to have salt-sensitive hypertension, with
• Individuals on antihypertensive treatment, and home blood pressure should be measured high glomerular blood pressure and a flatter pressure-diuresis curve.
to promote patient engagement in treatment and adherence. Hyperinsulinemia caused by insulin resistance is also involved in accel-
• In pregnant patients with diabetes and pre-existing hypertension treated with
antihypertensive therapy, systolic or diastolic blood pressure targets of 120-160/80-105
erating the reabsorption of sodium from the renal tubules. Excessive salt
mmHg is suggested to optimize long-term maternal health and fetal growth. intake inhibits nocturnal blood pressure reduction. Morning hypertension
• All hypertensive patients with diabetes should monitor home blood pressure to identify has a significantly higher frequency of developing nephropathy and ret-
white-coat hypertension. inopathy.
• Orthostatic measurement of blood pressure should be performed during the initial
evaluation of hypertension and periodically at follow-up, or when symptoms of
orthostatic hypotension are present, and regularly if orthostatic hypotension has been Rationale and Evidence 1238
diagnosed. • The Hypertension Optimal Treatment (HOT) trial 1231 was a large trial of
Dietary recommendations:
almost 19,000 patients randomized to a target diastolic BP of 90 mm Hg,
85 mm Hg, or 80 mm Hg. Felodipine was used as baseline therapy, with
• The American Heart Association recommends no more than 1500 mg of sodium/day as the addition of ACE inhibitors or β‐blockers and diuretics as needed. A
ideal.
• For seasoning of foods, herbs, spices, lemon, lime, vinegar, or salt-free seasoning blends
subgroup of 1501 with diabetes attained diastolic BPs of 85 mm Hg,
make a better choice than table salt. 83 mm Hg, and 81 mm Hg, respectively, with a 51% reduction in CV
• In rice and other cereal preparations like roti, and poori, do not mix salt. Avoid the use endpoints in the lower compared with the high BP group.
of salted rice, salted porridge, and other salted cereal mixes. • The Action in Diabetes and Vascular Disease: Preterax and Diamicron
• Avoid packaged mixes, canned soups, or broths - they generally have a high sodium
content.
Modified Release Controlled Evaluation (ADVANCE) trial,1231 eval-
• Use fresh vegetables. Avoid the use of canned vegetables as they contain salt uated antihypertensive therapy with the ACE inhibitor perindopril and
preservatives. the diuretic indapamide vs. placebo in patients with Type 2 diabetes
• Substitute fruits, salad, and fresh vegetables for salted snack foods. having a baseline BP 145/81 mm Hg. Mean BPs attained were 134/
• Limit the use of foods packed in brine, such as pickles, pickled vegetables, and olives.
• Use little or no sauces: avoid tomato ketchup, soy sauce, MSG, mustard sauce, and
74 mm Hg vs. 140/76 mm Hg, leading to a lower combined rate of
chutney. major macrovascular and microvascular events (15.5% vs. 16.8%), as
• Use fresh poultry, fish, and lean meat rather than the canned, smoked, or processed well as a reduction in CV mortality (3.8% vs. 4.6%) and all‐cause
types. mortality (7.3% vs. 8.5%).
• The BP arm of the Action to Control Cardiovascular Risk in Diabetes visits. Current ADA guidelines recommend a treatment goal of SBP <
(ACCORD) trial 1231 prospectively investigated whether lower BP at 140 mmHg and DBP < 90 mmHg for most patients with diabetes.
such levels further reduced CV events in high-risk patients with Type 2 • For individuals with diabetes and hypertension at higher cardiovascular
diabetes, followed during an 8-year period. In the hypertension arm of risk (existing atherosclerotic cardiovascular disease [ASCVD] or 10-
the trial, 4733 patients aged 40 to 79 with type 2 diabetes were randomly year ASCVD risk > 15%), a blood pressure target of < 130/80 mmHg
assigned to intensive therapy, targeting a systolic BP of<120 mm Hg, or may be appropriate if it can be safely attained.
standard therapy, targeting a BP of<140 mm Hg. The patients had • For individuals with diabetes and hypertension at lower risk for cardio-
diabetes for an average of 10 years. During the follow-up period of vascular disease (10-year atherosclerotic cardiovascular disease risk <
4.7 years, the average systolic BP was 119 mm Hg in the intensively 15%), treat to a blood pressure target of < 140/90 mmHg.
treated group and 133.5 mm Hg in the standard therapy group. No • In pregnant patients with diabetes and pre-existing hypertension, a blood
significant differences were found between the intensive group and pressure target of < 135/85 mmHg is suggested to reduce the risk for
the standard group in rates of a combined end point of nonfatal myo- accelerated maternal hypertension and minimize impaired fetal growth.
cardial infarction, nonfatal stroke, or death from CV causes (208 CV • For patients with blood pressure > 120/80 mmHg, lifestyle intervention
events in the intensive group, 237 events in the standard group) consists of weight loss if overweight or obese, a Dietary Approaches to
• The ADVANCE study was a 22-factorial intervention with both BP and Stop Hypertension (DASH)-style eating pattern including reducing so-
glycemia treatment, providing another opportunity to look at the com- dium and increasing potassium intake, moderating alcohol intake, and
bined effect of both interventions. During the duration of 4.3 years, BP increased physical activity.
was reduced by an average standard error of the mean of 10.3 mm Hg • Patients with confirmed office BP > 140/90 mmHg should adopt life-
systolic and 90.2 mm Hg diastolic in patients assigned to joint treatment style therapy and have prompt initiation and timely titration of pharma-
compared with those assigned to neither treatment (P<.001). Similarly, cologic therapy to achieve BP goals.
hemoglobin A1c was reduced by 0.61% to 0.02% after 4.3 years of • Patients with confirmed office BP > 160/100 mmHg should adopt
follow-up in patients assigned to joint therapy compared with those lifestyle therapy and have prompt initiation and timely titration of two
assigned to neither treatment (P<.001). Comparing the four resultant drugs or a single-pill combination of drugs demonstrated to reduce CV
groups, glucose-intensive and glucose-standard with and without events in patients with diabetes.
perindopril indapamide, patients assigned to both intensive glucose • An ACE inhibitor or ARB, at the maximum tolerated dose indicated for
and BP-lowering, compared with the standard glucose and placebo BP BP treatment, is the recommended first-line treatment for hypertension
intervention, had significant 18% and 24% reductions in total and CV in patients with diabetes and UACR > 300 mg/g creatinine (A) or 30–
mortality and a 28% reduction in renal events, in particular with 54% 299 mg/g creatinine (B). If one class is not tolerated, the class should be
reduction in the likelihood of new-onset macroalbuminuria. substituted.
• The large screening camping1239 conducted in India in 2017 and 2018, • For patients treated with an ACE inhibitor, ARB, or diuretic, serum
was named May Measurement Month (MMM). In 2017, it was found that, creatinine/eGFR and serum potassium levels should be monitored
out of the 122685 screeners for whom all three BP readings were available, annually.
38974 (31.8%) had hypertension based on the mean of the second and third • Selection of anti glycemic drugs also plays a vital role in hypertension
reading or the history of anti-hypertensive medication. A total of 17205 control and CV Risk reduction.
(14.0%, n=122 685) participants were on anti-hypertensive treatment.
Among 17205 participants receiving hypertension treatment, 14203 Risk Factors
(82.6%) had uncontrolled BP. In 2018, it was identified that out of all the Diabetes is associated with both macrovascular (involving large arteries
participants, 64.0% (n=221039) had measured their BP for the first time in such as conduit vessels) and microvascular (involving small arteries and
their life, and only 28.1% (n= 97 015) recorded their BP within the last 12 capillaries) disease. 1241 Chronic hyperglycemia and insulin resistance
months. 81% (n= 279 643) were not on antihypertensive medication. This play an essential role in the initiation of vascular complications of diabe-
screening campaign shows that the burden of hypertension in India is high, tes and involve several mechanisms, including increased formation of
and such initiatives help identify the hidden cases of hypertension. advanced glycation end products (AGEs) and activation of the receptor
• The other study conducted in India on middle-class urban subjects found a for advanced glycation end products (RAGE) AGE-RAGE axis, oxida-
low prevalence of normotension and high prevalence of hypertension1240. tive stress, and inflammation. Hypertension is a significant risk factor for
Normotensive individuals had a lower prevalence of cardiometabolic risk diabetes-associated vascular complications because hypertension itself is
factors than members of the prehypertensive or hypertensive groups. Half characterized by vascular dysfunction and injury.
of the hypertensive group were aware of having hypertension, a third were
receiving treatment for it, and a quarter had a controlled BP
Implementations
Clinical Management for Hypertension in Diabetics
• Blood pressure should be monitored at each visit.
• Use the non-dominant arm unless the dominant arm has 10 mmHg or
greater BP compared to the non-dominant.
• Adjust the settings to correspond to bedtime and time awake.
• Ask them to stop and stand still when a reading is being taken (if
possible).
• Test an initial reading to be sure it’s working.
• Use a proper-sized cuff.
• A thin sleeve over the arm and under the monitor helps prevent bruising.
ADA guidelines: blood pressure targets

Figure 21: Common Risk Factors
• The American Diabetes Association (ADA) defines hypertension as
Pathophysiology
SBP ≥ 140 mmHg and DBP ≥ 90 mmHg confirmed during separate clinic
The pathophysiology of hypertension in diabetes involves maladaptive Treatment Considerations

changes in the autonomic nervous system, vascular endothelial dysfunc- Treatment Goals
tion, enhanced activation of the renin-angiotensin-aldosterone system, For individuals with diabetes and hypertension at higher CV risk (existing
immune function alterations, and harmful environmental factors. 1242 ASCVD or 10-year ASCVD risk < 15%), a blood pressure target of <130/
80 mmHg may be appropriate if it can be safely attained. For individuals
with diabetes and hypertension at lower risk for CVD (10-year ASCVD
risk < 15 %), treat to a blood pressure target of < 140/90 mmHg.
ACEI and ARB are the first lines in the management of diabetic hyper-
tensives. ACEIs may be used alone for BP lowering but are much more
effective when combined with a thiazide-type diuretic or other antihyper-
tensive drugs. They reduce the macrovascular and microvascular risks
associated with diabetic hypertensives.
Calcium Channel Blockers (CCB) with Thiazide-like diuretics are

the second line of treatment.
The renin-angiotensin-aldosterone system is a major regulatory system of
CV and renal function. Thus, multiple clinical trials in past decades have
confirmed that suppression of renin-angiotensin-aldosterone system ac-
tivity might be expected to reduce CV mortality and all-cause mortality.
Despite the above findings, however, the cardioprotective effects of
renin-angiotensin-aldosterone system blockade were recently called into
question. The Non–Insulin-Dependent Diabetes, Hypertension,
Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril
(DIABHYCAR) study found that angiotensin-converting enzyme inhib-
itors (ACEIs) did not affect CV events in patients with type 2 DM and
albuminuria.1250 There was a higher rate of fatal CV events with
Olmesartan therapy among patients with type 2 DM in the Randomized
Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP)
study. 1251
Figure 22: Pathophysiology The American Diabetes Association recommends that patients with DM
Complications and hypertension should be treated with a pharmacologic therapy regimen
Patients with diabetes have more isolated systolic hypertension, have that includes an ACEI or an angiotensin II receptor blocker (ARB). If one
enhanced variability in BP, are prone to develop orthostatic hypotension, class of medication is not tolerated, the other class should be used. Both
and have HTN, which is more resistant to treatment. Experience less types of drugs limit the effects of angiotensin II, but the mechanisms of
reduction in nocturnal BP and higher baseline heart rates than their non- action are not identical. Thus, theoretically, there might be relevant dif-
diabetic counterparts because of autonomic neuropathy; BP control in ferences between the drug classes. The recent meta-analysis by Van Vark
these patients presents a significant challenge because the target BP is et al. showed that ACEIs or ARBs had different effects on all-cause
relatively low, and the response to treatment is often poor. Together these mortality in patients with hypertension. This difference might also exist
conditions fall under the umbrella of metabolic syndrome. And individ- in the treatment of DM. However, evaluating the relative effects of ACEIs
uals with metabolic syndrome are at increased risk for cardiovascular and ARBs is difficult due to inadequate head-to-head trials. In light of the
disease. above, we undertook the present meta-analysis aiming to overcome this
Arrhythmia during hypoglycemia is likely the reason for increased CVD limitation by evaluating the effect of ACEIs and ARBs separately vs.
deaths observed during strict blood glucose control. The relative risk of placebo or other medications on the incidence of all-cause mortality,
CVD occurring during severe hypoglycemia is reported to be 2.05-fold CV deaths, and CV events in patients with DM.1252
Microvascular complications:
Action in Diabetes and Vascular Disease: Preterax and Diamicron Prevention of Hypertension with diabetes
Controlled Evaluation (ADVANCE) trial cohort has confirmed that mi- 1 Optimal glycaemic control: While optimal glycemic control remains
crovascular complications increase the risk of cardiovascular complica- paramount in the prevention1242 of microvascular complications (reti-
tions in individuals with Type 2 diabetes. Moreover, the coexistence of nopathy, nephropathy, and neuropathy), concurrent cardiometabolic de-
hypertension and retinopathy is a risk factor for the progression of ne- rangements such as hypertension and dyslipidemia play a pivotal role in
phropathy. 1241 the initiation and progression of macrovascular disease (ischemic heart
disease, stroke, and peripheral vascular disease). Effective management
Orthostatic hypotension (decrease in systolic blood pressure of of diabetes should therefore include a multifaceted approach combining
20 mmHg or a reduction in diastolic blood pressure of 10 mmHg within optimal control of blood pressure and lipids with appropriate glycemic
3 mins of standing when compared with blood pressure from the sitting or control.
supine position) is common in people with Type 2 diabetes and hyper- 2. Dietary Approaches to Stop Hypertension trial (DASH)1244
tension. It is associated with an increased risk of mortality and heart Lifestyle modifications such as exercise and a diet low in sodium, satu-
failure. rated fat, and cholesterol and high in potassium, calcium, fiber, and fruits
have decreased BP. The DASH diet recommends keeping salt intake to
Considerations less than 2300 mg (1500 mg daily – elderly). The DASH study compared
In diabetic patients with hypertension, it has been argued that intensive three eating plans: A plan that includes foods people regularly eat without
BP control is more beneficial than tight glucose control. For stroke, any intervention; a plan that provides for regular food plus more fruits and
diabetic endpoint, death from diabetes, and microvascular complications, vegetables alone; and the DASH eating plan, i.e., diet more in potassium,
treating hypertension led to much more significant relative risk reductions fruits, fiber, calcium and less in sodium, saturated fat, and cholesterol. All
than treating hyperglycemia. 1243 three plans included about 3 000 mg of sodium daily. Participants who
followed the plan that included more fruits and vegetables and the DASH
Medical Nutrition Therapy

eating plan had reduced BP, but the DASH eating plan had better control. In elderly diabetics with obesity, medical nutrition therapy plays a significant role.
Foods with a low glycaemic index, complex carbohydrates, and high fiber are advised.
DIABETES IN ELDERLY Food supplements rich in protein and fiber and fortified with vitamins and minerals may be used.
• Food habits and foods available in the area should be discussed with the patient &
Recommendations
relatives.
• Body weight and sugar levels, and comorbidities should be taken into consideration.
General • Carbohydrate content should be limited to 50%‑60 % of total calorie intake. Complex
• India’s population of older adults, including those with diabetes, is increasing by carbohydrates and high fiber diet should be advised.
enormous proportions. • High glycaemic index foods should be discussed and their disadvantages should be
• Strong emphasis on cost-effectiveness and simplification of management strategies is explained.
needed for the care of diabetes in older adults. • Fiber intake should be about 25‑30 gm per day, but it should not result in diarrhea
• Motivational counseling, cognition enhancement, and social support should be essential • Protein intake should be maintained at about 15% of total calorie intake. The quantity of
tools to improve treatment compliance by older adult diabetic patients. protein intake depends on age, sarcopenia, and renal dysfunction.
• Because of significant heterogeneity among older adult diabetic patients, treatment should • Fat intake should be limited (<30% of total calorie intake). Avoid consumption of foods
be tailored according to individual needs to achieve desired glycemic goals. with high amounts of saturated fats (butter, coconut oil, margarine, ghee). Saturated fatty
• Improving subjective well-being and quality of life is an essential care component, acids (SFAs) intake should be less than 10% of total calories/day (<7% for individuals
particularly for older adult diabetic patients. having high triglycerides).
Geriatric Syndromes-detection and management • A diet rich in fruits, leafy vegetables, nuts, fiber, whole grains, and unsaturated fat should
• Many geriatric syndromes like dementia and frailty compromise the abilities of older be recommended.
diabetics to self-manage their disease and they begin depending on a caregiver. • The diet should include pulses, legumes, unprocessed vegetables, and low-fat dairy
• Older diabetics should undergo screening for early detection of neurocognitive impairment products.
and dementia annually or earlier if there is a deterioration in clinical status. Increasing • Overall salt consumption should be <5 g/day.
difficulty in self-management of diabetes should be regarded as a clinical deterioration. • Meal plans with strategic meal replacements (partial or complete) may be an option under
• Older diabetics should undergo screening for early detection of frailty, preferably even supervision when feasible.
before the pre-frail stage, so that its progress can be arrested or reversed, to improve Oral Antidiabetic Agents
diabetic care in older adults. Elderly diabetics are to be treated with tailor-made therapy. This will depend upon their
Lifestyle Management disabilities, comorbidities, support system and financial status. Elderly diabetics with physical
• Eating right is described in the chapter on medical nutrition therapy (MNT). Indian diet is high disabilities are given leverages for their physical condition. Nutrition and exercise play an
in carbohydrates and low in protein which promotes weight gain and central obesity on one essential role. A careful watch should be kept for drug interactions and ADRs. Recommendations
hand and muscle loss (sarcopenia) and frailty on the other. Frailty detection and its for the use of OADs in elderly diabetic patients are listed below.
management are dealt with in the chapter on geriatric syndromes. • Metformin- First line of drug, especially in obese diabetics.
• Physical activity and exercise lower blood glucose, promote cardiac function, improve muscle • Sulfonylureas- First/Second line of drug.
mass, prevent frailty, strengthen bone mass, and elevate mood. Independent and fit older • Meglitinides- May be given.
diabetics can engage in 150 minutes of brisk walking per week, roughly 30 minutes of walking • Alpha-Glucosidase Inhibitors- May be given.
each day for five days a week. On average, they should also be advised to perform muscle • Pioglitazone- May be used in low doses.
strengthening exercises three times a week. However, all exercises should be tailored under • DPP4 inhibitors- Good drug, weight neutral, renal & cardiac friendly except vildagliptin
medical advice, and the extent and type of physical activity recommended should consider in CLD.
cardiorespiratory reserve and the status of joints, bones, vision, nerves, muscles, etc. • Oral GLP- 1 Receptor Agonist- in obese Diabetics
Usually, if one can count his pulse rate or record by finger pulse meter, he can check that • SGLT2 inhibitors- Recommended for up to 70 years of average weight/obese elderly,
joint exercises like brisk walking should not raise the heart rate beyond 95 to 120 per helpful in patients with diastolic dysfunction.
minute for those aged 50-60 years, 85 to 110 per minute for those aged 60-70 years and 80
to 105 per minute for those aged more than 70 years1254.
• Stress management and promoting good sleep in older diabetics can be achieved by de-
stressing mechanisms like meditation, music, social networking, befriending
grandchildren, etc. Sleep hygiene includes going to bed at least 1-2 hours after dinner,
avoiding daytime naps, keeping the room free from noise and bright light, avoiding TV,
coffee, tea, and alcohol, and drinking excess water before sleep. Sound sleep is good for
preventing or controlling many diseases like diabetes, high blood pressure, heart disease,
stroke, depression, dementia, etc.
• Older diabetics should be subjected to periodic health check-ups as a thorough medical
examination, including necessary laboratory tests. Checking and monitoring all
medications, assessment of teeth, nutrition, urinary problem, depression, and physical and
mental disabilities like impaired vision, mobility, hearing, and memory should be a part of
health check-up1255. The need for any vaccination, especially the pneumococcal and flu
vaccination, is also important1256.
• Miscellaneous steps include avoiding excess alcohol, self-medication, exposure to
pollution, smoke, dust, and weather extremes. House should be well ventilated, and inside
the house, there should not be any poor lighting, slippery and wet floors, loose fitting
carpets, cluttering of furniture, any stairs without railings, or toilets without support grips
because all of these make the elderly vulnerable to falls, injuries, and fractures.
Injectables
• Injectable therapies like insulin and GLP1RA offer reasonable glycaemic control in elderly
financial dimensions, all of which can seriously impact diabetes care.
diabetics if used with caution, and the appropriate patient selection is made judiciously. India’s population trajectory between the years 2000 and 2050 indicates
• Starting low and going slow should be the mantra to avoid adverse effects. a 55% increase in total population from 1008 to 1572 million but a 326%
• Patient and caregiver education, monitoring, and regular follow-ups are the key to the
increase of 60+ (76 to 324 million) and a 700% increase of 80+ individ-
success of injectable therapies in elderly diabetics.
• Ultra long-acting insulins like degludeg and glargine U300 are the insulins of choice in uals (6 to 48 million)1257. The magnitude of diabetes among older adults
elderly diabetics. in India is also enormous, including old and young onset diabetes, which
• Newer ultra short-acting prandial insulins are preferable to cover prandial peaks. is carried forward to 60+ age. Roughly a quarter of people in their 70s and
• In case of frequent hypoglycaemic events, especially nocturnal hypos, the nighttime
prandial insulin should be stopped.
80s are diabetic, and in addition, many are in pre-diabetic stage.
• The type of insulin and the insulin regimen(e.g., basal only, basal plus, basal-bolus, or According to Longitudinal Ageing Study in India (LASI), the self-
premix) should be chosen based on individual patient characteristics. reported prevalence of diabetes mellitus among Indian adults aged 45-
• SMBG (self-monitoring of blood glucose) and Individualised insulin titration charts are 59 was found to be 9% while among the older adults aged 60 and above it
the keys to sustained euglycemia.
• GLP1RA, like dulaglutide, lixisenatide, and liraglutide, offers the same pleiotropic was 14%1258. In terms of the global diabetes epidemic, India ranks second
benefits even in elderly diabetics. Starting with the lowest dose possible and slow up- after China with 77 million people with diabetes. Of these, 12.1 million
titration will allow for better tolerability of these agents in elderly diabetics. are aged >65 years, which is estimated to increase to 27.5 million in the
Hypoglycemia in Elderly
• Hypoglycemia and its unawareness is more common among older diabetics than young
year 20451259.
diabetics and is fraught with dreadful consequences. Primary care physician needs to realize that majority of older adults in
• Hypoglycemia in the elderly is defined as any blood sugar level below 70 mg/dl, and a India have financial limitations, are rural based or living under marginal-
glucose value of 70–100 mg/ dL should raise the alarm of the need to change or adjust the ized conditions, and that the advancing age brings about some impair-
regimen. Although HbA1c alone should not be the sole criteria for glycemic control,
HBA1c < 7.0 should also be taken as a warning for overtreatment
ment of cognitive understanding, a fatalistic attitude, and a lack of will
• Liberal relaxation of glycemic targets is essential to avoid hypoglycemia among older and motivation that is enough to interfere with the compliance of medical
diabetics who are functionally dependent or/and are under long-term or end-of-life care. advice given to him. Further, management of diabetes in old age has to be
Even functionally independent older patients are vulnerable to hypoglycemia if tight blood
individualized since the care of older diabetics is complicated by wide
glucose control is attempted. Oral hypoglycemic agents can also be withdrawn amongst
them if there is a high risk of hypoglycemia. heterogeneity among these patients1260. Such heterogeneity could be with
• An individualized care plan is required, including t h e d e s i r e d blood glucose range respect to the level of their physical and mental functioning, expected life
to minimize the risk of hypoglycemia. This includes both pharmacological and non- expectancies, duration of diabetes, the prevalence of chronic complica-
pharmacological treatment.
• Among OHAs, sulfonylureas are not the preferred class of drugs as they can cause
tions, and relative burden of co-morbidities like hypertension, heart dis-
hypoglycemia. Still, if at all, shorter-acting sulfonylureas like gliclazide and glipizide ease, stroke, arthritis, cognitive impairment, incident falls, chronic kid-
should be used, but the longer-acting ones like glibenclamide and chlorpropamide should ney, liver and pulmonary diseases. Economic, social, and emotional dep-
not be used. Glinides group of OHAs are to be avoided. Glitazones have a low risk of
rivation also affects some but not others. Consequences of aging like
causing hypoglycemia, yet it is better to avoid in the elderly for the risk of fluid retention,
increased incidence of bone fractures, and bladder cancer. Metformin and DPP4 inhibitors higher cardiovascular risk, wider glycaemic variability, increased risk of
are relatively safe in older diabetics. SGLT2 inhibitors do not cause hypoglycemia but hypoglycaemia, greater deleterious effects of persistent hyperglycaemia,
should be used cautiously in frail older populations for the risk of further weight loss. altered pharmacokinetics, and differentials in the type of living arrange-
• Among the injectables, insulin should be prescribed only after evaluation of
administering abilities, regular glucose monitoring, and understanding of hypoglycemia.
ment (e. g. with family, living alone, or in old age home) also determine
GLP1 agonists may not increase hypoglycemia risk, but their cost and weight loss limit the therapeutic strategy for older diabetics.1261 In fact, RSSDI determined
their use in the elderly diabetic population. advancing age as one of the important factors in the patient-centric ap-
• The non-pharmacological approach comprises proper nutrition therapy, immediate control proach for individualization of diabetic management and included it in
of fever if present and training of carers for recognition and treatment of hypoglycemia.
their diagrammatic representation termed as RSSDI-ESI Therapeutic
Wheel1262. In short, management of diabetes in old age demands a ratio-
Treatment Goals
• Although glycemic targets are based on HbA1c, in the uncommon instances of anemia, nal choice of antidiabetic agents and an easily understood simplified
polycythemia, hemoglobinopathies, hemodialysis, or recent blood loss or transfusion, this regimen that would achieve the desired glycaemic goals with or without
parameter may be misleading. the support of a trained informal or formal caregiver.
• Elderly diabetics should be regularly assessed for physical function, cognitive impairment,
microvascular complications, frailty, and comorbidities to set the glycaemic targets.
Care of diabetes in older adults becomes more difficult in the presence of
• Elderly diabetics and their caregivers should be assessed for disease managing skills for certain complex clinical conditions, the geriatric syndromes which tradi-
diabetes care and be given education. tionally comprise the 5 ‘Is’ that is Impaired intellect (confusion, delirium,
• Elderly diabetics with good quality of life with either none or very mild microvascular and dementia), Imbalance (with resulting falls and fractures), Immobility
complications with a life expectancy of at least 10 to 15 years should have an A1C target
of 7 -7.5%.
(associated with frailty, sarcopenia, and impaired lower extremity perfor-
• Those with diabetes with moderate cognitive impairments, microvascular complications, mance), Incontinence (multiple etiology) and Impaired vision and hear-
and comorbid conditions should have an A1C target of 7.5-8.5%. ing. Other common geriatric syndromes include polypharmacy and de-
• The elderly with advanced microvascular complications and /or major comorbid illness
pression while sleep disorders like insomnia and sleep apnoea have been
and /or life expectancy of fewer than five years may have an A1C target of >8.5%. Such
people should be treated only to prevent osmotic symptoms, infection control, or modify recently added to the list1263.
cardiovascular risk factors. Furthermore, caring for an older diabetic is far more than keeping
• For older adults with type 1 diabetes, continuous glucose monitoring should be considered sugar, lipids, and blood pressure under control. The primary phy-
mainly for those at risk of hypoglycemia, including insulin deficiency necessitating insulin
therapy, progressive renal insufficiency, etc.
sician also needs to ensure subjective well-being and good mental
• For patients receiving palliative and end-of-life care, the focus should be on avoiding health for the remaining period of life, especially for an older
hypoglycaemia and symptomatic hyperglycemia while reducing the burden of glycaemic individual. Ordinarily, many older adults have psychological and
management. Thus, as organ failure develops, several agents will have to be de intensified
social problems, but when it comes to people in their 90s and 100s,
or discontinued. For the dying patient, most agents for type 2 diabetes may be removed.
Treatment Simplification Regimens many studies have observed that despite declining physical health,
Timely simplification and deintensification of complex treatment regimens in elderly diabetics go nonagenarians and centenarians have better mental health compared
a long way in reducing adverse events, improving the compliance and quality of life (QOL) of an
individual. Implementing the available screening tools to access the safety of polypharmacy will
to younger adults1264,1265. Since better resilience and adaptability
help the clinician in selecting a regimen which is simple, safe and most beneficial to an elderly attained from their long-standing coping abilities, bonding with
diabetic. Based on the overall health status of an elderly patient, the appropriate treatment family for social support, and connecting with religion are thought
simplification or deintensification should be done.
to be determinants for better mental health and longer life span,
both formal and informal care providers need to build and strength-
A. General en these determinants through well-accepted methods in order to
Globally, the burgeoning population of older adults poses diverse health preserve a good quality of life for older individuals with diabetes
challenges that include medical, cognitive, psychological, social, and also.
B. Diabetes And Geriatric Syndromes listening to older diabetics and their families, holding motivational inter-
The phenotype of diabetes in old age is characterized by an increased views, careful counselling, encouraging a behavioural change in the pa-
prevalence of multiple geriatric syndromes. Geriatric syndromes are com- tient, and prescribing simple and easily understood treatment.
mon clinical conditions that do not fit into specific disease categories but Compliance will also improve if the older adult patient is advised to
have the substantial quality of life implications for the functionality of the enhance his cognition through brain challenging activities like new read-
older individuals1266. A long list of these syndromes includes cognitive ing, befriending grandchildren, playing puzzles, learning a new skill such
impairment leading to dementia, frailty, and polypharmacy as the com- as a musical instrument, computer, a language, and through social net-
mon ones, and the last one of these three is described in the chapter on working. Health care has evolved from HCPs giving orders to patients, to
treatment simplification. Others include urinary incontinence, depression, HCPs educating and working out a compromise with patients. In other
imbalance, and resulting falls while new ones such as sleep disorders words, we have to learn to “wheel and deal” with our patients to find the
comprising insomnia and sleep apnoea have been added to the list1263. best compromise for better outcomes1274.
Most geriatric syndromes complicate the care of older diabetics by inter-
fering with their self-managing abilities and quality of life. General D. Medical Nutrition Therapy
screening by comprehensive geriatric assessment1267 helps detect not Over the years the stress was on the control of blood glucose levels by
only locomotor, visual, and hearing impairment but also provides early pharmacotherapy which included insulin and OHAs. After realizing that
indication for the presence of many geriatric syndromes which can be nutrition always plays a vital role in metabolism, the stress is on medical
specifically screened by well-defined tools if necessary. nutrition therapy (MNT) also1275. MNT is in fact a component of lifestyle
management but given its considerable importance, it has been described
Neurocognitive decline leading to dementia: Prevalence of irreversible here as a separate topic.
dementias like Alzheimer’s and vascular dementia is more common Dietary advice should take into account age-related alterations in appetite,
among older diabetics compared to older non-diabetics. Even though taste, smell, and difficulties in chewing, swallowing, or digestion.
good diabetic control is no guarantee against continuing cognitive de- Comorbidities like obesity, hypertension, and dyslipidaemia and avail-
cline, both poor control and a longer duration of diabetes worsen the able support system also determine nutritional therapy in the elderly.
cognitive impairment. Yet it is important to screen every older diabetic 46 percent of type 2 diabetes are overweight or obese. With obesity in
to detect early cognitive impairment because self-managing abilities to patients with diabetes, there is an increased risk of hypertension, chronic
care for diabetes and quality of life will get increasingly compromised kidney disease (CKD) cardiovascular disease (CVD). In overweight or
with the progression of dementia. Abilities that may be compromised obese patients with diabetes, the rate of complications is also higher by 2-
include forgetting to take medicines, meals, and their contents as pre- 4 percent than in the normal population. A 10 percent reduction in body
scribed or incorrectly calculating or administering the insulin dose. weight significantly reduces the risk factors associated with diabetes.
Hindi Mini Mental Status Examination1268 and Mini-cog examination1269 Medical nutritional therapy is most vital in the elderly, especially at the
are useful for screening for cognitive decline followed by further referral stage of prediabetes and if they are obese1276.
for neuropsychological evaluation if needed. Although uncommon, the In Asia, particularly in India, we have a high carbohydrate diet and a high
primary physician also needs to evaluate older diabetics for reversible percentage of our energy requirement comes from carbohydrates only. A
dementias such as vitamin B12 deficiency consequent to long-term met- weight-reducing diet, rich in fibre & complex carbohydrates that are
formin therapy and chronic hyponatremia. slowly digested, helps in reducing postprandial peaks as well as weight.
Frailty: Frailty is an important condition in old age that is characterized Food items with a high glycaemic index should be avoided. Meal replace-
by a reduction of physiological reserve and reduction in the ability to ments both partial and full mean replacements are given when the patient
resist physical and psychological stressors1270. Frailty is associated with is unable to eat properly or has an aversion for food due to reasons
weight loss, weakness, exhaustion, decreased physical activity, slowness including mood swings.1277
of gait, and undernutrition. Sarcopenia is a part of frailty and means As far as diet is concerned most elderly diabetics have quantity of protein
reduced muscle protein synthesis, a result of lower testosterone and which is less than one gram per kilogram of their body weight. They have
IGF-1 and increased muscle protein breakdown due to chronic hypergly- a high carbohydrate diet and generally have a sweet tooth. It is because
cemia and inflammation and is associated with insulin resistance. Frailty this reason that their sugar levels swing a lot. The addition of proteins
and its risk can be measured1271,1272. Management of frailty in diabetes (vegetarian and non-vegetarian) is the best option, but, there are commer-
includes optimal nutrition with adequate protein intake combined with an cially available medical nutrition items that are rich in protein, fortified
exercise program that includes aerobic, weight-bearing, and resistance with vitamins and minerals, and have fibre elements also.1278
training under medical supervision. Weight-reducing anti-diabetic agents
should not be used in frail diabetics and staging of frailty (prefrail or frail) E. ORAL ANTIDIABETIC AGENTS
should be taken into account while individualizing anti-diabetic therapy From the point of view of management, we divide elderly diabetics into
for appropriate glycaemic targets. three segments: the fit elderly, the elderly with compromised activities of
daily living and/or with comorbidities1279 and the elderly who are totally
C. Lifestyle Management dependent upon care givers.
Lifestyle management (LSM) is the fundamental and cost-effective prin- Due consideration is given to disabilities which may be physical, cogni-
ciple of caring for diabetes at all ages and is an essential component of all tive, or psychological. One must keep in mind the ongoing pharmaco-
clinical practice guidelines1273. If practiced well, it is always useful in therapy of comorbidities which may raise the issues of polypharmacy1280,
preventing and controlling diabetes and many other lifestyle disorders. drug interactions and increased adverse drug reactions (ADRs). The phys-
LSM is also essential even if diabetes is being pharmacologically treated ically fit/gainfully employed segment of the elderly are offered treatment
by blood glucose-lowering agents. Basically, LSM comprises eating with stringent controls while the targets of the elderly with compromised
right, exercising well, managing stress, sleeping full, accessing regular ADL1281 are liberal.
health care, and resorting to certain miscellaneous steps. The management starts with physical check-ups and assessments of cer-
tain body functions. Support system, easy regimens & economy always
Issue of compliance to LSM among older diabetics have consideration. Besides the advice on lifestyle, pharmacotherapy
Cognitive and psychological changes of aging associated with a fatalistic with oral antidiabetic drugs (OADs)1282 is an important part of diabetic
attitude and decreased alertness and drive make the older individual less management. The following table illustrates the advantages and disad-
compliant to the advice of a primary physician. This requires a greater vantages of different OADs,
Table 45: Advantages and Disadvantages of medications Prandial insulins are newer ultra short-acting insulins like aspart,
glulisine, and lispro which can be used to control prandial peaks. In
Medication Advantage Disadvantage elderly diabetics with frequent nocturnal hypos, it is better to avoid pran-
Low risk of
Cannot be used in advanced CRF. dial insulin before dinner. Prandial doses can be given before breakfast
hypoglycaemia,
Metformin cardiovascular benefit,
Increased risk of lactic acidosis in those and lunch. The prandial glycemic target can be between 180—220 mg/dl
with renal impairment, heart failure and
weight based on the overall health status of an elderly diabetic. As with basal
sepsis. Causes dyspepsia and flatulence.
neutral/reducing. insulin, the dose of prandial insulin can be titrated based on pre-meal
Potent, economical glucose values. If pre-meal glucose is above 250 mg/dl, 2 units of insulin
suitable for those with
Sulfonylureas renal impairment can
Hypoglycaemia – especially long-acting, can be increased, and if it is above 350 mg/dl, an increment of 4 units
be added with other
Wight Gain. daily can be done until the glycemic target is achieved1285. In case of
OADs. frequent hypos and if the prandial dose is below 10 IU, other non-insulin
Short-acting, better for drug options should be initiated.
PP hyperglycaemia &,
and suitable for those Risk of hypoglycaemia and weight gain
Meglitinides
with unplanned eating but less than sulfonylureas.
Pre-mix insulins include an NPH and a short-acting prandial component
behaviour e.g. geriatric in different compositions like 30/70, 25/75,50/50. Twice daily dosing
patients1283. (before breakfast and dinner) is sufficient, reducing the number of daily
Low risk of weight Weak hypoglycaemic action, injections compared to a basal-bolus regimen. But, there is more glycemic
Alpha-Glucosidase
gain and gastrointestinal side effects especially
Inhibitors variability and less TIR (time in range) with premix insulins, increasing
hypoglycaemia. bulky stools.
Works as an insulin the chances of hypoglycemia. If there are frequent hypos in elderly dia-
sensitizer, suitable for Fluid retention worsens heart failure, betics using premix insulin, 70 % of the total premix dose can be given as
Pioglitazone those with renal increases fracture risk, and possibly a single, morning-time basal insulin dose.
impairment, and less bladder cancer.
risk of hypoglycaemia.
GLP1RA THERAPY IN ELDERLY DIABETICS:
Gastrointestinal side effects, dose mostly
Low risk of needs to be adjusted with renal Incretin-based therapies including dipeptidyl peptidase-4 inhibitors and
DPP-4 Inhibitors hypoglycaemia, weight impairment except in the case of glucagon-like peptide-1 (GLP-1) receptor agonists stimulate insulin se-
neutral. linagliptin. Vildagliptin is not to be used cretion in a glucose-dependent manner resulting in a lower risk of
in CLD. hypoglycaemia when used as monotherapy or in combination with agents
Oral GLP-1 Receptor Low risk of
Agonist hypoglycaemia, and Not suitable for frail elderly.
that do not increase insulin levels1286, and could therefore be a good
(Semaglutide)1284 weight loss. alternative for the elderly, especially overweight and obese.
GLP-1 receptor agonists have demonstrated pleotrophic benefits in pa-
Sodium Glucose Low risk of Not suitable for frail elderly, increases
Cotransporter 2 hypoglycaemia, weight risk of urinary tract infections, candidiasis tients with atherosclerotic cardiovascular disease (ASCVD) and those at
(SGLT2) Inhibitors loss & BP Reduction. & dehydration. higher ASCVD risk, and newer trials are expanding our understanding of
their benefits in other populations. In a systematic review and meta-
analysis of GLP-1 receptor agonist trials, these agents have been found
F. INJECTABLES to reduce major adverse cardiovascular events, cardiovascular deaths,
Insulin and GLP1 receptor agonists are the two classes of injectable stroke, and myocardial infarction to the same degree for patients above
therapy options for diabetic patients. In elderly diabetics, drugs with and below 65 years of age1287. While the evidence for this class for older
low a risk of hypoglycemia are preferred. Insulin and GLP1RA are potent patients continues to grow, there are several practical issues that should be
anti-diabetic drugs giving an HBA1C reduction to the tune of up to 1.5 %. considered for older patients. These drugs are injectable agents, which
If used with proper caution and monitoring, these agents can offer good require visual, motor, and cognitive skills for appropriate administration.
glycemic control without hypoglycemia in elderly diabetics. Common adverse events with GLP1RA are nausea, vomiting, and diar-
Additionally, GLP1RA offers cardiovascular benefit, renal benefit, and rhoea. Given the gastrointestinal side effects of this class, GLP-1 receptor
improvement in BP and lipid parameters, especially in overweight or agonists may not be preferred in older patients who are experiencing
obese elderly diabetics. unexplained weight loss.
It has been reported that patients with T2D have a higher incidence of
INSULIN THERAPY IN ELDERLY DIABETICS: cognitive decline and T2D is associated with an increased risk of demen-
Apart from conventional NPH and Regular short-acting insulin, we now tia and Alzheimer's disease development1288. High glucose levels in
have newer insulins with smooth glycemic control, which help to reduce themselves are also thought to have detrimental effects on the aging brain
glycemic variability and hypoglycemia episodes. At the time of insulin and may be associated with an increased risk of dementia in populations
initiation, patient and caregiver education regarding the pen device, ad- both with and without diabetes. Conversely, stringent glycaemic control
ministration technique, insulin injection sites, hypoglycemia symptoms, in elderly patients may result in hypoglycaemia, which may also have
and management is very vital. The cognitive and functional status of the detrimental effects on cognitive function and cognitive impairment in
patient should also be considered. itself also increases the risk of hypoglycaemia. It is therefore important
to consider a treatment regimen that not only is effective in HbA1c re-
Basal insulins are long-acting insulins like Glargine U100, Detemir, and duction but also has demonstrated low incidences of hypoglycaemia.
ultra-long-acting insulins like U300 and Degludeg and offer peakless Dulaglutide, Lixisenatide, and Liraglutide are the three injectable
round-the-clock glycemic control. They are usually given at bedtime. In GLP1RA available in India. Semaglutide is the only oral GLP1RA.
elderly diabetics, the starting dose should be lesser than the typical 0.2 IU/
kg/day. One needs to start with a lower dose and up titrate based on the Dulaglutide is a human GLP-1 receptor agonist, with a half-life of ∼5
individualized insulin titration chart. The FPG (fasting plasma glucose) days allowing once-weekly dosing. It is administered with a single-use
target for the elderly can be between 90—150 mg/dl. If there is a frequent pen with no requirement for reconstitution or dialing of a dose1289 . It is
incidence of hypoglycemia, especially nocturnal hypoglycemia, the basal not renally excreted and pharmacokinetic studies have shown that neither
insulin can be shifted to the morning dose (after breakfast)1285. If the FPG age nor renal function affects its actions, thus no dose adjustment is
target stays above the goal, one can increase 2 units of basal insulin. required in these settings. Starting dose is 0.75 mg subcutaneous after
Similarly, if FPG is below the target, can decrease 2 units of basal insulin. dinner once a week for initial 4 weeks. Then, it can be upitrated to 1.5mg
The patient needs to be followed up once in 2 weeks. weekly based on the tolerability and GI side effects.
LIRAGLUTIDE: It is a once-daily subcutaneous GLP1RA. The usual Other drugs that need attention in the elderly are used of glinides and
starting dose is 0.6mg daily. But, in elderly diabetics, one can start with a insulin, especially in frail older patients or elderly patients with multiple
lower dose of 0.3 mg and up titrate every 2 weeks based on tolerability. In co-morbidities where their nutrition is poor, they are carer dependent and
a study comprising elderly diabetics, liraglutide improved glycaemic con- regular glucose monitoring may not be feasible. Education strategy
trol, lipid profile, and visceral obesity for 3 years. In addition, the hippo- should be developed for the carer in terms of proper nutrition for the
campal atrophy and arteriosclerosis were not deteriorated, suggesting the patient and regular monitoring of blood glucose levels. Also, it should
possibility of being effective for the prevention of dementia.1290 In an- be reinforced on each visit for better implementation
other study, twenty-four weeks of liraglutide treatment was associated Furthermore, HbA1c may be misleading in the elderly population due to
with reductions in fat mass and android fat. In addition, to prevent sarco- anemia, thalassemia, polycythemia, hemoglobinopathies, hemodialysis
penia, it preserved the muscular tropism.1291 or recent blood loss1303,1304 and hypoglycemia may not be recognized.
LIXISENATIDE: It is a GLP1RA given once daily. It has a short half- H. Treatment Goals
life and is useful as a prandial GLP1RA, generally given before the major Treatment goals for relatively healthy elderly diabetics with good cogni-
meal of the day. The optimum daily dose of Lixisenatide is 20 micro- tive and physical functioning are same as for young diabetics i.e. HbA1c
grams subcutaneous. In a meta-analysis conducted on data from older <7% but for many elderly diabetics, these need to be relaxed i.e. HbA1c
patients (≥65 years) from five of the GetGoal trials, in which patients 7-8 or even 9%1305. The concept of relaxing the goals finds support from
with T2DM were treated with lixisenatide 20 μg once daily as an add- the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
on to OADs, lixisenatide improved glycaemic control with respect to in which HbA1c of < 6% was associated with increased mortality.
HBA1C, FPG and PPG.1292 1306
This should not however imply clinical inertia on the part of treating
clinicians and desired glycaemic goals at a minimum should avoid the
G. Hypoglycemia In Elderly deleterious consequence of persistent hyperglycaemia namely, dehydra-
Care of the older adults with diabetes is complicated by their clinical, tion, hyperosmolar coma, incontinence, cognitive decline, poor wound
cognitive and functional heterogeneity. Hypoglycemia is one of the major healing, sarcopenia, visual disturbances, and poor lower extremity per-
limiting factors when trying to achieve recommended levels of glycemic formance. Table 1 summarizes HbA1c-related glycaemic targets for el-
control at any age1293,1294. The elderly population also has a high preva- derly diabetics as per the severity of their cognitive impairment, and
lence of cardiovascular morbidity which can be aggravated by hypogly- physical and functional health1261.
cemia. A fine balance needs to be achieved by individualization of ther-
apy so that hypoglycemia can be avoided and simultaneously, the burden Table 46: Glycaemic targets for elderly diabetics according to cogni-
of hyperglycemic complications can be reduced. tive impairment, and physical and functional health.
Hypoglycemia in the elderly is defined as any blood sugar level below 70
mg/dl. Incidence of hypoglycemia in older people (>75 years) with dia- Parameter Category Category patient Category
patient one two Patient three
betes is difficult to estimate due to the limited number of clinical studies Cognitive impairment Nil Moderate Severe
and the lack of standardization in hypoglycemia diagnosis. Tight control Functional status Independent Dependent Dependent
of blood sugar can result in undesirable hypoglycemia1295 which in older General Health Fair Intermediate Poor
Physical health
patients has a higher risk of poor outcomes due to altered adaptive phys-
Frail No Yes Yes
iologic responses to low glucose levels1296,1297. Microvascular Minimal Moderate Advanced
Hypoglycemia unawareness is also common in older adults and increases complications and Minimal Moderate Advanced
the risk of silent hy Comorbidities
Life expectancy >10-15 years <5 years <5 years
hypoglycemia that remains unrecognized1298 both by symptoms as well HbA1c target 7-7.5% 7.5-8.5% >8.5%
as finger stick glucose measurement. Aging modifies the counter- Notes: 1. A common goal is to keep glycaemic variability at a minimum to avoid hyper and
regulatory and symptomatic responses to hypoglycemia. Many hypogly- hypoglycaemia. 2. Cardiovascular risk reduction is a part of diabetic management. Control of
cemic episodes are mild or even asymptomatic and are not likely to be hypertension among diabetics is useful1307. Statin and aspirin are prescribed on an individual basis
and for patients above age 70 or 80, primary prevention with aspirin is not recommended.
reported. However, a severe single episode of hypoglycemia may result in
serious acute consequences such as seizure, coma, and cardiac arrhyth-
mias. It also has a bidirectional relationship with cognitive dysfunction I. TREATMENT SIMPLIFICATION REGIMENS
and leads to poor outcomes1299. With aging, concomitant diseases and conditions along with diabetes
Other devastating complications of hypoglycemia that leads to a decline become more frequent. Eventually, the elderly diabetics end up taking
in quality of life include an increase in falls and fractures, fear of falling, multiple daily drugs. Since the complexity of treatment regimens and
confusion, delirium, and symptoms such as fatigue and dizziness1300. polypharmacy may interfere with self-caring abilities and lead to serious
Thus, in older adults, it is crucial that individualized care and treatment adverse events, the treatment modification approach should be
strategies include early recognition and management of hypoglycemia considered1308.
and in turn, glycemic targets can be adjusted based on the patient’s func- Polypharmacy is defined as more than ten medications during hospital
tional, cognitive, and disease status. admission, or more than five medications at discharge used appropriately
Risk factors for hypoglycemia in older people with diabetes include lon- based on current evidence-based medicine or the use of inappropriate
ger duration, insulin treatment and some sulfonylureas, polypharmacy, medications and medications without any clinical benefit1309. A study
erratic meals, insufficient carbohydrate intake, renal impairment, liver of Swedish elderly found that 39% were taking five or more drugs con-
impairment, cognitive impairment, malabsorption or slowed intestinal comitantly1310. Before prescribing any new medication for a condition,
absorption and swallowing problems, and last but not the least, it could we need to understand the goals of the patient, caregiver, and the medi-
be blocked PEG tube. cation's benefit over risk ratio.
Avoiding medications with a high risk of hypoglycemia is a reasonable Deintensification or deprescribing refers to decreasing the dose or fre-
first step in the prevention of hypoglycemia. Sulfonylureas especially quency of administration of a treatment or discontinuing treatment alto-
chlorpropamide and glibenclamide should be avoided in the elderly. gether. Simplification and deintensification of complex treatment regi-
Glibenclamide (also known as glyburide) has been classified as a poten- mens is recommended in elderly diabetics to reduce the risk of
tially inappropriate medication in older adults by the American Society of hypoglycaemia and polypharmacy, provided it can be achieved within
Geriatrics1301 and has been replaced with gliclazide by the World Health the individualized A1C target. Treatment regimen simplification results
Organization in the diabetes section of the list of essential medicines.1302
in fewer administration times, fewer blood glucose checks and decreases

the need for calculations (e.g. insulin-carbohydrate ratio calculations).
Implementing the available screening tools to identify and assess the
safety of polypharmacy in elderly age groups is the first step in mitigating
the risk. The various tools which can be used in various settings include
NO TEARS tool 1310 , Hyperpharmacotherapy Assessment Tool
(HAT)1310, Beers Criteria1311, Screening Tool of Older Person's poten-
tially inappropriate Prescriptions (STOPP), Medication Appropriateness
Index (MAI)1312,1313 and Anticholinergic Drug Scale1314.
Table 47 :Simple therapeutic options for elderly diabetics according

to their functional status1315.
Option Independent Dependent frail Dependent demented

(Category I) (Category II) (Category III)
Diet Restrict Calories, protein Calories should be
carbohydrates intake should be adequate
adequate
Exercise Muscle strengthening Muscle Normal Activities
strengthening
BW (body weight) Healthy BW No No
reduction
Metformin 1st line st
1 line 1st line
Caution in patients Caution in patients with
with CKD,CHF, CKD, CHF, sarcopenia,
sarcopenia, and GI and GI side effects
side effects Figure 22: Algorithm for insulin regimen simplification
Sulphonylurea(SU) 2ndline Alternate 1st line +/-
J. Long-Term Care And The End-Of-Life Care
Low dose SU can be
used as an alternate Long-term care (LT) facilities are scarce in India. Older patients with
1st line agent in frail diabetes who require long-term care are often the residents of old-age
patients with homes in this country. Although their categorization in terms of function-
metformin al severity is variable, when compared to community-dwelling elderly
intolerance
Insulin 2ndline Long acting analog Long acting analog
diabetics, old age home resident diabetics are less likely to be independent
Thiazolidinediones 2ndline +/- +/- and fit individuals. Approach to care for diabetes is therefore tailored
To be avoided in To be avoided in according to individual patients in old age homes also. Choice of antidi-
patients with H/O patients with H/O abetic agents and glycaemic targets are set accordingly. More precisely,
fractures, CHF. fractures, CHF.
Spontaneous reports Spontaneous reports of
International Diabetes Federation has identified three groups of older
of macular edema macular edema were patients with diabetes to facilitate better management. Category 1 in-
were found. found1316. cludes the functionally independent individuals who do not require sup-
DPP 4-I 2ndline +/- +/- port. Category 2 includes functionally dependent individuals and has
GLP1-RA 2nd or 3rd line To be avoided for +/-
been divided into frail and those with dementia. Category 3 has been
potential GI side Cost is the major factor
effects and weight identified as those individuals who are terminally ill and in need of end-
loss of-life care1317. Category 3 is described below under end-of-life care.
Meglitinides 2ndline +/- To be avoided in Long-term care facilities for diabetes care should have an available nurse
demented patients with and be given mandatory sensitization training for LTC staff, caregivers,
erratic eating habits, for
fear of hypoglycemia.
and the primary physician who is often skilled for only community-
AGI 2ndline To be avoided for +/- dwelling and hospitalized older diabetic patients. The nurse should stress
potential GI side the importance of complying with the prescribed treatment program
effects and weight through effective patient education and emphasize the importance of the
loss
effect of blood glucose control on long-term health. LTC patients do not
have the benefit of frequent advice from their primary physician who
Although SGLT2 inhibitors do not cause hypoglycaemia, they are visits them only at fixed intervals e. g. weekly or fortnightly. LTC facil-
avoided in frail elderly for fear of weight loss. ities should have their own points when to suspect emergencies such as
In case of severe/recurrent episodes of hypoglycemia or an increase in hypoglycaemia and acute complications of hyperglycaemia like dehydra-
glycaemic variability, the insulin regimen to be stopped in frail and de- tion and confusion and should be able to provide first aid in such situa-
mented category patients. tions. LTC staff should also be able to contact a primary physician for
Insulin treatment is one of those antidiabetic agents which has consider- timely advice. Emergency indications for shifting the patient for hospital
able potential to cause hypoglycaemia and add to the complexity of the admission should be clearly laid down. General principles of treatment of
treatment regimen. The following table gives an algorithm for insulin older diabetics on long-term care comprise an easily understood simpli-
simplification regimen1285. fied treatment regimen which consists of OHAs with low risk of
hypoglycaemia, basal insulin if required, and avoidance of undernutrition
and weight loss. If pre-meal insulin is needed, it may be better to give it
after the meal to match the amount of ingested carbohydrates. The sole
use of sliding scale insulin (SSI) should be avoided1318.
End-of-life care is the approach to a terminally ill patient that shifts the
focus of care to symptom control, comfort, dignity, quality of life, and
quality of dying rather than treatments aimed at cure or prolongation of
life.1319 Such care is therefore often based on palliative therapy, may be
provided at home, hospice, hospital, or any other setting, and may last for Diagnosis of Diabetes and Prediabetes among High-risk South Indians.
days to weeks1320 but sometimes may extend to several months. Indian J Endocrinol Metab [Internet]. 2018 Jan 1 [cited 2022
End-of-life care for people with diabetes should not be viewed as a failure Aug 5];22(1):50. Available from: /pmc/articles/PMC5838911/
of care, but as a complement to usual diabetes care. The general aims are 12. Prakaschandra R, Prakesh Naidoo D. Fasting Plasma Glucose and the
to consider ethical and legal aspects of care, improve and maintain dignity HbA1c Are Not Optimal Screening Modalities for the Diagnosis of New
and quality of life, help the person achieve life goals, manage pain and Diabetes in Previously Undiagnosed Asian Indian Community
distressing symptoms, and talk honestly about prognosis and the person’s Participants. Ethn Dis [Internet]. 2018 Dec 1 [cited 2022
concerns, values, and goals, achieve a dignified death in a place of the Aug 5];28(1):19–24. Available from: https://pubmed.ncbi.nlm.nih.gov/
person’s choosing, and support family and carers.1321 Principles of end- 29467562/
of-life care for older diabetics include relaxing the goals of blood sugar 13. Kumar PR, Bhansali A, Ravikiran M, Bhansali S, Dutta P, Thakur JS,
and blood pressure targets, avoiding hypoglycaemia and undue et al. Utility of glycated hemoglobin in diagnosing type 2 diabetes
hyperglycaemia and its effects like dehydration and confusion. Statins mellitus: a community-based study. J Clin Endocrinol Metab [Internet].
can be stopped unless essential. Unnecessary diagnostic procedures 2010 [cited 2022 Aug 5];95(6):2832–5. Available from: https://
should be discouraged and only required doses of OHAs and basal insulin pubmed.ncbi.nlm.nih.gov/20371663/
may be administered. 14. Mohan V, Vijayachandrika V, Gokulakrishnan K, Anjana RM,
Ganesan A, Weber MB, et al. A1C cut points to define various glucose
References intolerance groups in Asian Indians. Diabetes Care [Internet]. 2010 Mar
1. Tirimacco R, Tideman PA, Dunbar J, Simpson PA, Philpot B, [cited 2022 Aug 5];33(3):515–9. Available from: https://
Laatikainen T, et al. Should capillary blood glucose measurements be pubmed.ncbi.nlm.nih.gov/19903752/
used in population surveys? Int J Diabetes Mellit. 2010 Apr;2(1):24–7. 15. CLASSIFICATION OF DIABETES MELLITUS 2019
2. Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, Kirkman Classification of diabetes mellitus [Internet]. 2019. Available from:
MS, et al. Position statement executive summary: guidelines and recom- http://apps.who.int/bookorders.
mendations for laboratory analysis in the diagnosis and management of 16. Das S. Lean Type 2 Diabetes Mellitus : Profile, Peculiarities and
diabetes mellitus. Diabetes Care. 2011 Jun;34(6):1419–23. Paradox.
3. Nguyen KA, Peer N, de Villiers A, Mukasa B, Matsha TE, Mills EJ, 17. Das S, Fonseca V. Low bodyweight Type 2 diabetes in India: Clinical
et al. Glycated haemoglobin threshold for dysglycaemia screening, and characteristics and pathophysiology. Diabetes & Metabolic Syndrome:
application to metabolic syndrome diagnosis in HIV-infected Africans. Clinical Research & Reviews. 2009 Jan 1;3(1):60–6.
PLoS One. 2019 Jan 1;14(1). 18. Lontchi-Yimagou E, Dasgupta R, Anoop S, Kehlenbrink S, Koppaka
4. Nathan DM, Balkau B, Bonora E, Borch-Johnsen K, Buse JB, S, Goyal A, et al. An Atypical Form of Diabetes Among Individuals With
Colagiuri S, et al. International Expert Committee Report on the Role Low BMI. Diabetes Care [Internet]. 2022 Jun 2 [cited 2022
of the A1C Assay in the Diagnosis of Diabetes. Diabetes Care Aug 5];45(6):1428–37. Available from: http://www.ncbi.nlm.nih.gov/
[Internet]. 2009 Jul [cited 2022 Aug 5];32(7):1327. Available from: pubmed/35522035
/pmc/articles/PMC2699715/ 19. Ahlqvist E, Storm P, Käräjämäki A, Martinell M, Dorkhan M,
5. Lauritzen T, Sandbaek A, Skriver M v., Borch-Johnsen K. HbA 1cand Carlsson A, et al. Novel subgroups of adult-onset diabetes and their
cardiovascular risk score identify people who may benefit from preven- association with outcomes: a data-driven cluster analysis of six variables.
tive interventions: A 7 year follow-up of a high-risk screening programme Lancet Diabetes Endocrinol [Internet]. 2018 May 1 [cited 2022
for diabetes in primary care (ADDITION), Denmark. Diabetologia. 2011 Aug 5];6(5):361–9. Available from: https://pubmed.ncbi.nlm.nih.gov/
Jun;54(6):1318–26. 29503172/
6. Hasslacher C, Kulozik F, Platten I, Lorenzo Bermejo J. Glycated albu- 20. Anjana RM, Baskar V, Nair ATN, Jebarani S, Siddiqui MK, Pradeepa
min and HbA1c as predictors of mortality and vascular complications in R, et al. Novel subgroups of type 2 diabetes and their association with
type 2 diabetes patients with normal and moderately impaired renal func- microvascular outcomes in an Asian Indian population: a data-driven
tion: 5-year results from a 380 patient cohort. J Diabetes Res Clin Metab cluster analysis: the INSPIRED study. BMJ Open Diabetes Res Care
[Internet]. 2014 Oct 30 [cited 2022 Aug 5];3(1):9. Available from: http:// [Internet]. 2020 Aug 17 [cited 2022 Aug 5];8(1). Available from:
www.hoajonline.com/jdrcm/2050-0866/3/9 https://pubmed.ncbi.nlm.nih.gov/32816869/
7. Lim WY, Ma S, Heng D, Tai ES, Khoo CM, Loh TP. Screening for 21. Anjana RM, Siddiqui MK, Jebarani S, Vignesh MA, Kamal Raj N,
diabetes with HbA1c: Test performance of HbA1c compared to fasting Unnikrishnan R, et al. Prescribing patterns and response to
plasma glucose among Chinese, Malay and Indian community residents antihyperglycemic agents among novel clusters of type 2 diabetes in
in Singapore. Sci Rep [Internet]. 2018 Dec 1 [cited 2022 Aug 5];8(1). Asian Indians. Diabetes Technol Ther [Internet]. 2022 Mar 14 [cited
Available from: https://pubmed.ncbi.nlm.nih.gov/30127499/ 2022 Aug 5];24(3):190–200. Available from: https://
8. Guo F, Moellering DR, Garvey WT. Use of HbA1c for diagnoses of discovery.dundee.ac.uk/en/publications/prescribing-patterns-and-re-
diabetes and prediabetes: Comparison with diagnoses based on fasting sponse-to-antihyperglycemic-agents-amo
and 2-Hr glucose values and effects of gender, race, and age. Metab 22. Bennett Peter H., Knowler William C. Definition, Diagnosis, and
Syndr Relat Disord. 2014 Jun 1;12(5):258–68. Classification of Diabete Mellitus and Glucose Homestasis. In: Kahn C
9. Hardikar PS, Joshi SM, Bhat DS, Raut DA, Katre PA, Lubree HG, Ronald, Weir Gordon. C, editors. Joslin’s Diabetes Mellitus. Fourteenth
et al. Spuriously high prevalence of prediabetes diagnosed by HbA(1c) in Edition. Philadelphia, Pa: Lippincott Williams & Willkins, 2005; 2005. p.
young indians partly explained by hematological factors and iron defi- 331–40.
ciency anemia. Diabetes Care [Internet]. 2012 Feb 8 [cited 2022 23. WC K, E BC, SE F, RF H, JM L, EA W, et al. Reduction in the
Aug 5];35(4):797–802. Available from: https://www.ncbi.nlm.nih.gov/ incidence of type 2 diabetes with lifestyle intervention or metformin. N
pmc/articles/pmid/22323413/?tool=EBI Engl J Med [Internet]. 2002 Feb 7 [cited 2022 Aug 7];346(6):393–403.
10. Madhu S v., Raj A, Gupta S, Giri S, Rusia U. Effect of iron deficiency Available from: https://pubmed.ncbi.nlm.nih.gov/11832527/
anemia and iron supplementation on HbA1c levels - Implications for 24. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in
diagnosis of prediabetes and diabetes mellitus in Asian Indians. Clin utero and early-life conditions on adult health and disease. N Engl J Med
Chim Acta [Internet]. 2017 May 1 [cited 2022 Aug 5];468:225–9. [Internet]. 2008 Jul 3 [cited 2022 Aug 7];359(1):61–73. Available from:
Available from: https://pubmed.ncbi.nlm.nih.gov/27717800/ https://pubmed.ncbi.nlm.nih.gov/18596274/
11. Radhakrishna P, Vinod KV, Sujiv A, Swaminathan RP. Comparison 25. Stephenson J, Heslehurst N, Hall J, Schoenaker DAJM, Hutchinson J,
of Hemoglobin A1c with Fasting and 2-h Plasma Glucose Tests for Cade JE, et al. Before the beginning: nutrition and lifestyle in the
preconception period and its importance for future health. Lancet 40. Fall CHD, Stein CE, Kumaran K, Cox V, Osmond C, Barker DJP,
[Internet]. 2018 May 5 [cited 2022 Aug 7];391(10132):1830–41. et al. Size at birth, maternal weight, and Type 2 diabetes in South India.
Available from: https://pubmed.ncbi.nlm.nih.gov/29673873/ Diabetic Medicine. 1998 Mar;15(3):220–7.
26. Yajnik C, Ganpule-Rao A, Limaye T, Rajgara F. Developmental 41. Bavdekar A, Yajnik CS, Fall CHD, Bapat S, Pandit AN, Deshpande
Origins of Non-Communicable Diseases. Proc Indian Natn Sci Acad. V, et al. Insulin resistance syndrome in 8-year-old Indian children: small
2016;82(5):1465–76. at birth, big at 8 years, or both? Diabetes [Internet]. 1999 [cited 2022
27. Su L, Patti ME. Paternal Nongenetic Intergenerational Transmission Aug 7];48(12):2422–9. Available from: https://
of Metabolic Disease Risk. Curr Diab Rep. 2019 Jul 24;19(7):38. pubmed.ncbi.nlm.nih.gov/10580432/
28. Hales CN, Barker DJP. Type 2 (non-insulin-dependent) diabetes 42. Yajnik CS, Deshpande SS, Jackson AA, Refsum H, Rao S, Fisher DJ,
mellitus: the thrifty phenotype hypothesis. Diabetologia [Internet]. 1992 et al. Vitamin B12 and folate concentrations during pregnancy and insulin
Jul [cited 2022 Aug 7];35(7):595–601. Available from: https:// resistance in the offspring: the Pune Maternal Nutrition Study.
pubmed.ncbi.nlm.nih.gov/1644236/ Diabetologia. 2008 Jan 13;51(1):29–38.
29. Freinkel N. Banting Lecture 1980. Of pregnancy and progeny. 43. Wagh RH, Bawdekar RU, Alenaini W, Fall CHD, Thomas EL, Bell
Diabetes [Internet]. 1980 [cited 2022 Aug 7];29(12):1023–35. JD, et al. Maternal Micronutrient Status in Pregnancy is Associated with
Available from: https://pubmed.ncbi.nlm.nih.gov/7002669/ Child’s Adiposity at 18yrs of age. J Dev Orig Health Dis. 2019
30. Wells JC, Sawaya AL, Wibaek R, Mwangome M, Poullas MS, Dec 3;10(S1):S1–313.
Yajnik CS, et al. The double burden of malnutrition: aetiological path- 44. Yajnik CS, Bandopadhyay S, Bhalerao A, Bhat DS, Phatak SB,
ways and consequences for health. Lancet [Internet]. 2020 Jan 4 [cited Wagh RH, et al. Poor In Utero Growth, and Reduced β-Cell
2022 Aug 7];395(10217):75–88. Available from: https:// Compensation and High Fasting Glucose From Childhood, Are
pubmed.ncbi.nlm.nih.gov/31852605/ Harbingers of Glucose Intolerance in Young Indians. Diabetes Care
31. Yajnik CS, Fall CHD, Coyaji KJ, Hirve SS, Rao S, Barker DJP, et al. [Internet]. 2021 Dec 1 [cited 2022 Aug 7];44(12):2747–57. Available
Neonatal anthropometry: the thin-fat Indian baby. The Pune Maternal from: https://pubmed.ncbi.nlm.nih.gov/34610922/
Nutrition Study. Int J Obes Relat Metab Disord [Internet]. 2003 Feb 1 45. Wagle SS, Phatak S, Ambardekar S, Dattatrey B, Deshmukh MK,
[cited 2022 Aug 7];27(2):173–80. Available from: https:// Kamat R, et al. Overweight-Obesity And Glucose Intolerance In
pubmed.ncbi.nlm.nih.gov/12586996/ Offspring Of Indian Diabetic Mothers. medRxiv [Internet]. 2021
32. van Steijn L, Karamali NS, Kanhai HHH, Ariëns GAM, Fall CHD, Nov 27 [cited 2022 Aug 7];2021.05.17.21257222. Available from:
Yajnik CS, et al. Neonatal anthropometry: thin-fat phenotype in fourth to https://www.medrxiv.org/content/10.1101/2021.05.17.21257222v2
fifth generation South Asian neonates in Surinam. Int J Obes (Lond) 46. Home - International Society for Development Origins of Health and
[Internet]. 2009 [cited 2022 Aug 7];33(11):1326–9. Available from: Disease International Society for Development Origins of Health and
https://pubmed.ncbi.nlm.nih.gov/19636321/ Disease [Internet]. [cited 2022 Aug 7]. Available from: https://
33. D’Angelo S, Yajnik CS, Kumaran K, Joglekar C, Lubree H, Crozier dohadsoc.org/
SR, et al. Body size and body composition: a comparison of children in 47. Kumaran K, Yajnik P, Lubree H, Joglekar C, Bhat D, Katre P, et al.
India and the UK through infancy and early childhood. J Epidemiol The Pune Rural Intervention in Young Adolescents (PRIYA) study:
Community Health (1978) [Internet]. 2015 Jul 16 [cited 2022 Design and methods of a randomised controlled trial. BMC Nutr
Aug 7];69(12):1147. Available from: /pmc/articles/PMC4645449/ [Internet]. 2017 Dec 22 [cited 2022 Aug 7];3(1):1–12. Available from:
34. Lakshmi S, Metcalf B, Joglekar C, Yajnik CS, Fall CH, Wilkin TJ. https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-017-0143-5
Differences in body composition and metabolic status between white 48. D’souza N, Behere R v., Patni B, Deshpande M, Bhat D, Bhalerao A,
U.K. and Asian Indian children (EarlyBird 24 and the Pune Maternal et al. Pre-conceptional Maternal Vitamin B12 Supplementation Improves
Nutrition Study). Pediatr Obes [Internet]. 2012 Oct [cited 2022 Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial. Front
Aug 7];7(5):347–54. Available from: https://pubmed.ncbi.nlm.nih.gov/ Pediatr [Internet]. 2021 Dec 7 [cited 2022 Aug 7];9:755977–755977.
22941936/ Available from: https://europepmc.org/articles/PMC8697851
35. Banerji MA, Faridi N, Atluri R, Chaiken RL, Lebovitz HE. Body 49. Trilok-Kumar G, Kaur M, Rehman AM, Arora H, Rajput MM,
Composition, Visceral Fat, Leptin, and Insulin Resistance in Asian Indian Chugh R, et al. Effects of vitamin D supplementation in infancy on
Men. J Clin Endocrinol Metab [Internet]. 1999 Jan 1 [cited 2022 growth, bone parameters, body composition and gross motor develop-
Aug 7];84(1):137–44. Available from: https://academic.oup.com/jcem/ ment at age 3–6 years: follow-up of a randomized controlled trial. Int J
article/84/1/137/2866189 Epidemiol [Internet]. 2015 Jun 1 [cited 2022 Aug 7];44(3):894–905.
36. Deurenberg-Yap M, Chew SK, Deurenberg P. Elevated body fat Available from: https://academic.oup.com/ije/article/44/3/894/633173
percentage and cardiovascular risks at low body mass index levels among 50. Kumaran K, Krishnaveni G v., Suryanarayana KG, Prasad MP,
Singaporean Chinese, Malays and Indians. Obes Rev [Internet]. 2002 Belavendra A, Atkinson S, et al. Protocol for a cluster randomised trial
[cited 2022 Aug 7];3(3):209–15. Available from: https:// evaluating a multifaceted intervention starting preconceptionally-Early
pubmed.ncbi.nlm.nih.gov/12164474/ Interventions to Support Trajectories for Healthy Life in India
37. Yajnik CS, Yudkin JS. The Y-Y paradox. Lancet [Internet]. 2004 (EINSTEIN): a Healthy Life Trajectories Initiative (HeLTI) Study.
Jan 10 [cited 2022 Aug 7];363(9403):163. Available from: https:// BMJ Open [Internet]. 2021 Feb 16 [cited 2022 Aug 7];11(2). Available
pubmed.ncbi.nlm.nih.gov/14726172/ from: https://pubmed.ncbi.nlm.nih.gov/33593789/
38. Bhargava SK, Sachdev HS, Fall CHD, Osmond C, Lakshmy R, 51. Home :: National Health Mission [Internet]. [cited 2022 Aug 7].
Barker DJP, et al. Relation of serial changes in childhood body-mass Available from: https://nhm.gov.in/
index to impaired glucose tolerance in young adulthood. N Engl J Med 52. Fleming TP, Watkins AJ, Velazquez MA, Mathers JC, Prentice AM,
[Internet]. 2004 Feb 26 [cited 2022 Aug 7];350(9):865–75. Available Stephenson J, et al. Origins of lifetime health around the time of concep-
from: https://pubmed.ncbi.nlm.nih.gov/14985484/ tion: causes and consequences. Lancet [Internet]. 2018 May 5 [cited 2022
39. Raghupathy P, Antonisamy B, Geethanjali FS, Saperia J, Leary SD, Aug 7];391(10132):1842. Available from: /pmc/articles/PMC5975952/
Priya G, et al. Glucose tolerance, insulin resistance and insulin secretion 53. IDF Diabetes Atlas | Tenth Edition [Internet]. [cited 2022 Aug 7].
in young south Indian adults: Relationships to parental size, neonatal size Available from: https://diabetesatlas.org/
and childhood body mass index. Diabetes Res Clin Pract. 2010 54. Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK,
Feb;87(2):283–92. et al. Prevalence of diabetes and prediabetes in 15 states of India: results
from the ICMR-INDIAB population-based cross-sectional study. Lancet
Diabetes Endocrinol [Internet]. 2017 Aug 1 [cited 2022 Aug 7];5(8):585– 67. Bennett CM, Guo M, Dharmage SC. HbA(1c) as a screening tool for
96. Available from: https://pubmed.ncbi.nlm.nih.gov/28601585/ detection of Type 2 diabetes: a systematic review. Diabet Med [Internet].
55. Nanditha A, Snehalatha C, Satheesh K, Susairaj P, Simon M, Vijaya 2007 Apr [cited 2022 Aug 7];24(4):333–43. Available from: https://
L, et al. Secular TRends in DiabEtes in India (STRiDE-I): Change in pubmed.ncbi.nlm.nih.gov/17367307/
Prevalence in 10 Years Among Urban and Rural Populations in Tamil 68. Group TDC and CTR. The Effect of Intensive Treatment of Diabetes
Nadu. Diabetes Care [Internet]. 2019 Mar 1 [cited 2022 on the Development and Progression of Long-Term Complications in
Aug 7];42(3):476–85. Available from: https://pubmed.ncbi.nlm.nih.gov/ Insulin-Dependent Diabetes Mellitus. https://doi.org/101056/
30659076/ NEJM199309303291401 [Internet]. 1993 Sep 30 [cited 2022
56. Cefalu WT, Buse JB, Tuomilehto J, Alexander Fleming G, Ferrannini Aug 7];329(14):977–86. Available from: https://www.nejm.org/doi/full/
E, Gerstein HC, et al. Update and Next Steps for Real-World Translation 10.1056/nejm199309303291401
of Interventions for Type 2 Diabetes Prevention: Reflections From a 69. Sacks DB. Global harmonization of hemoglobin A1c. Clin Chem
Diabetes Care Editors’ Expert Forum. Diabetes Care [Internet]. 2016 [Internet]. 2005 Apr [cited 2022 Aug 7];51(4):681–3. Available from:
Jul 1 [cited 2022 Aug 7];39(7):1186–201. Available from: https:// https://pubmed.ncbi.nlm.nih.gov/15788784/
pubmed.ncbi.nlm.nih.gov/27631469/ 70. Nanditha A, Susairaj P, Raghavan A, Vinitha R, Satheesh K, Nair
57. Kaur G, Chauhan AS, Prinja S, Teerawattananon Y, Muniyandi M, DR, et al. Concordance in incidence of diabetes among persons with
Rastogi A, et al. Cost-effectiveness of population-based screening for prediabetes detected using either oral glucose tolerance test or glycated
diabetes and hypertension in India: an economic modelling study. haemoglobin. Prim Care Diabetes [Internet]. 2022 Jun 1 [cited 2022
Lancet Public Health [Internet]. 2022 Jan 1 [cited 2022 Aug 7];16(3). Available from: https://pubmed.ncbi.nlm.nih.gov/
Aug 7];7(1):e65–73. Available from: https://pubmed.ncbi.nlm.nih.gov/ 35337771/
34774219/ 71. Association AD. Diagnosis and Classification of Diabetes Mellitus.
58. Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Diabetes Care [Internet]. 2014 Jan 1 [cited 2022
Vijay V. The Indian Diabetes Prevention Programme shows that lifestyle Aug 7];37(Supplement_1):S81–90. Available from: https://
modification and metformin prevent type 2 diabetes in Asian Indian sub- diabetesjournals.org/care/article/37/Supplement_1/S81/37753/
jects with impaired glucose tolerance (IDPP-1). Diabetologia [Internet]. Diagnosis-and-Classification-of-Diabetes-Mellitus
2006 Feb [cited 2022 Sep 1];49(2):289–97. Available from: https:// 72. Choudhury AA, Devi Rajeswari V. Gestational diabetes mellitus - A
pubmed.ncbi.nlm.nih.gov/16391903/ metabolic and reproductive disorder. Biomed Pharmacother [Internet].
59. Nanditha A, Snehalatha C, Raghavan A, Vinitha R, Satheesh K, 2021 Nov 1 [cited 2022 Aug 7];143. Available from: https://
Susairaj P, et al. The post-trial analysis of the Indian SMS diabetes pre- pubmed.ncbi.nlm.nih.gov/34560536/
vention study shows persistent beneficial effects of lifestyle intervention. 73. Misra A, Ramachandran A, Saboo B, Kesavadev J, Sosale A, Joshi S,
Diabetes Res Clin Pract [Internet]. 2018 Aug 1 [cited 2022 Sep et al. Screening for diabetes in India should be initiated at 25 years age.
1];142:213–21. Available from: https://pubmed.ncbi.nlm.nih.gov/ Diabetes Metab Syndr [Internet]. 2021 Nov 1 [cited 2022 Aug 7];15(6).
29859274/ Available from: https://pubmed.ncbi.nlm.nih.gov/34739907/
60. Weber MB, Ranjani H, Meyers GC, Mohan V, Narayan KMV. A 74. Nanditha A, Snehalatha C, Raghavan A, Vinitha R, Satheesh K,
model of translational research for diabetes prevention in low and middle- Susairaj P, et al. The post-trial analysis of the Indian SMS diabetes pre-
income countries: The Diabetes Community Lifestyle Improvement vention study shows persistent beneficial effects of lifestyle intervention.
Program (D-CLIP) trial. Prim Care Diabetes [Internet]. 2012 Apr [cited Diabetes Res Clin Pract [Internet]. 2018 Aug 1 [cited 2022
2022 Sep 1];6(1):3–9. Available from: https://pubmed.ncbi.nlm.nih.gov/ Aug 7];142:213–21. Available from: https://pubmed.ncbi.nlm.nih.gov/
21616737/ 29859274/
61. Screening for Type 2 Diabetes Report of a World Health Organization 75. Hostalek U, Campbell I. Metformin for diabetes prevention: update of
and International Diabetes Federation meeting World Health the evidence base. Curr Med Res Opin [Internet]. 2021 [cited 2022
Organization Department of Noncommunicable Disease Management Aug 7];37(10):1705–17. Available from: https://
Geneva. 2003; pubmed.ncbi.nlm.nih.gov/34281467/
62. Chapter-80 Strategies for Prevention of Type 2 Diabetes Mellitus_ 76. Ramachandran A, Snehalatha C, Mohan V, Viswanathan M.
Evidences from Indian Studies. Remission in NIDDM. In: Proceedings of the International Symposium
63. Mohan V, Deepa R, Deepa M, Somannavar S, Datta M. Original on Epidemiology of Diabetes mellitus. Bangkok, Thailand; 1987. p. 185–
Article# A Simplified Indian Diabetes Risk Score for Screening for 9.
Undiagnosed Diabetic Subjects. [cited 2022 Aug 7]; Available from: 77. Riddle MC, Cefalu WT, Evans PH, Gerstein HC, Nauck MA, Oh
www.japi.org759 WK, et al. Consensus Report: Definition and Interpretation of Remission
64. Ramachandran A, Snehalatha C, Vijay V, Wareham NJ, Colagiuri S. in Type 2 Diabetes. Diabetes Care. 2021 Oct 1;44(10):2438–44.
Derivation and validation of diabetes risk score for urban Asian Indians. 78. Kalra S, Singal A, Lathia T. What’s in a Name? Redefining Type 2
Diabetes Res Clin Pract [Internet]. 2005 Oct [cited 2022 Diabetes Remission. Diabetes Therapy. 2021 Mar 24;12(3):647–54.
Aug 7];70(1):63–70. Available from: https://pubmed.ncbi.nlm.nih.gov/ 79. Kahn R, Hicks J, Muller M, Panteghini M, John G, Deeb L, et al.
16126124/ Consensus statement on the worldwide standardization of the hemoglobin
65. Somannavar S, Ganesan A, Deepa M, Datta M, Mohan V. Random A1C measurement: the American Diabetes Association, European
capillary blood glucose cut points for diabetes and pre-diabetes derived Association for the Study of Diabetes, International Federation of
from community-based opportunistic screening in India. Diabetes Care Clinical Chemistry and Laboratory Medicine, and the International
[Internet]. 2009 Apr [cited 2022 Aug 7];32(4):641–3. Available from: Diabetes Federation. Diabetes Care [Internet]. 2007 Sep [cited 2022
https://pubmed.ncbi.nlm.nih.gov/19073758/ Aug 7];30(9):2399–400. Available from: https://
66. Susairaj P, Snehalatha C, Raghavan A, Nanditha A, Vinitha R, pubmed.ncbi.nlm.nih.gov/17726190/
Satheesh K, et al. Cut-off Value of Random Blood Glucose among 80. Jeppsson JO, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, et al.
Asian Indians for Preliminary Screening of Persons with Prediabetes Approved IFCC reference method for the measurement of HbA1c in
and Undetected Type 2 Diabetes Defined by the Glycosylated human blood. Clin Chem Lab Med [Internet]. 2002 [cited 2022
Haemoglobin Criteria. J Diabetes Clin Res [Internet]. 2019 [cited 2022 Aug 7];40(1):78–89. Available from: https://pubmed.ncbi.nlm.nih.gov/
Aug 7];1(2). Available from: https://www.scientificarchives.com/journal/ 11916276/
journal-of-diabetes-and-clinical-research 81. Weykamp C, John WG, English E, Erasmus RT, Sacks DB, Buchta
C, et al. EurA1c: The European HbA1c Trial to Investigate the
Performance of HbA1c Assays in 2166 Laboratories across 17 Countries Mechanisms. Diabetes Spectr [Internet]. 2012 Nov 11 [cited 2022
and 24 Manufacturers by Use of the IFCC Model for Quality Targets. Aug 8];25(4):200. Available from: /pmc/articles/PMC3527013/
Clin Chem [Internet]. 2018 Aug 1 [cited 2022 Aug 7];64(8):1183–92. 95. Salminen P, Helmio M, Ovaska J, Juuti A, Leivonen M, Peromaa-
Available from: https://pubmed.ncbi.nlm.nih.gov/29921723/ Haavisto P, et al. Effect of Laparoscopic Sleeve Gastrectomy vs
82. Beck RW, Connor CG, Mullen DM, Wesley DM, Bergenstal RM. Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years
The Fallacy of Average: How Using HbA 1c Alone to Assess Glycemic Among Patients With Morbid Obesity: The SLEEVEPASS
Control Can Be Misleading. Diabetes Care [Internet]. 2017 Aug 1 [cited Randomized Clinical Trial. JAMA [Internet]. 2018 Jan 16 [cited 2022
2022 Aug 7];40(8):994–9. Available from: https:// Aug 8];319(3):241–54. Available from: https://
pubmed.ncbi.nlm.nih.gov/28733374/ pubmed.ncbi.nlm.nih.gov/29340676/
83. Shah VN, Dubose SN, Li Z, Beck RW, Peters AL, Weinstock RS, 96. Dyson PA, Twenefour D, Breen C, Duncan A, Elvin E, Goff L, et al.
et al. Continuous Glucose Monitoring Profiles in Healthy Nondiabetic Diabetes UK evidence-based nutrition guidelines for the prevention and
Participants: A Multicenter Prospective Study. J Clin Endocrinol Metab management of diabetes. Diabet Med [Internet]. 2018 May 1 [cited 2022
[Internet]. 2019 Oct 1 [cited 2022 Aug 7];104(10):4356–64. Available Sep 15];35(5):541–7. Available from: https://pubmed.ncbi.nlm.nih.gov/
from: https://pubmed.ncbi.nlm.nih.gov/31127824/ 29443421/
84. Murphy R, Jiang Y, Booth M, Babor R, Maccormick A, Hammodat 97. Karter AJ, Nundy S, Parker MM, Moffet HH, Huang ES. Incidence of
H, et al. Progression of diabetic retinopathy after bariatric surgery. Diabet remission in adults with type 2 diabetes: the diabetes & aging study.
Med [Internet]. 2015 Sep 1 [cited 2022 Aug 7];32(9):1212–20. Available Diabetes Care [Internet]. 2014 Dec 1 [cited 2022 Aug 8];37(12):3188–
from: https://pubmed.ncbi.nlm.nih.gov/25689226/ 95. Available from: https://pubmed.ncbi.nlm.nih.gov/25231895/
85. Roy Taylor - Reversing the irrevesible: Type 2 diabetes and you. 4th 98. Jennings AS, Lovett AJ, George TM, Jennings JS. Getting to goal in
Oct 2014 [Internet]. [cited 2022 Aug 8]. Available from: https:// newly diagnosed type 2 diabetes using combination drug “subtraction
campus.recap.ncl.ac.uk/Panopto/Pages/Embed.aspx?id=c3bef819-e5f4- therapy.” Metabolism. 2015 Sep 1;64(9):1005–12.
4a55-876f-0a23436988ed 99. Forouhi NG, Misra A, Mohan V, Taylor R, Yancy W. Dietary and
86. Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, nutritional approaches for prevention and management of type 2 diabetes.
et al. Weight and type 2 diabetes after bariatric surgery: systematic review BMJ [Internet]. 2018 [cited 2022 Aug 9];361. Available from: https://
and meta-analysis. Am J Med [Internet]. 2009 Mar [cited 2022 pubmed.ncbi.nlm.nih.gov/29898883/
Aug 8];122(3). Available from: https://pubmed.ncbi.nlm.nih.gov/ 100. Dixit AA, Azar KMJ, Gardner CD, Palaniappan LP. Incorporation
19272486/ of whole, ancient grains into a modern Asian Indian diet to reduce the
87. Daigle CR, Chaudhry R, Boules M, Corcelles R, Kroh M, Schauer burden of chronic disease. Nutr Rev [Internet]. 2011 Aug [cited 2022
PR, et al. Revisional bariatric surgery can improve refractory metabolic Aug 9];69(8):479–88. Available from: https://pubmed.ncbi.nlm.nih.gov/
disease. Surgery for Obesity and Related Diseases. 2016 Feb;12(2):392– 21790614/
7. 101. Misra A, Singhal N, Sivakumar B, Bhagat N, Jaiswal A, Khurana L.
88. Adams TD, Davidson LE, Litwin SE, Kolotkin RL, LaMonte MJ, Nutrition transition in India: Secular trends in dietary intake and their
Pendleton RC, et al. Health benefits of gastric bypass surgery after 6 relationship to diet-related non-communicable diseases. J Diabetes.
years. JAMA [Internet]. 2012 Sep 12 [cited 2022 2011 Dec;3(4):278–92.
Aug 8];308(11):1122–31. Available from: https:// 102. Popkin BM. Nutrition Transition and the Global Diabetes Epidemic.
pubmed.ncbi.nlm.nih.gov/22990271/ Curr Diab Rep [Internet]. 2015 Sep 27 [cited 2022 Aug 9];15(9):64.
89. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer Available from: /pmc/articles/PMC4942180/
SA, et al. Bariatric Surgery versus Intensive Medical Therapy for 103. Davies MJ, D’Alessio DA, Fradkin J, Kernan WN, Mathieu C,
Diabetes - 5-Year Outcomes. N Engl J Med [Internet]. 2017 Feb 16 [cited Mingrone G, et al. Management of Hyperglycemia in Type 2 Diabetes,
2022 Aug 8];376(7):641–51. Available from: https:// 2018. A Consensus Report by the American Diabetes Association (ADA)
pubmed.ncbi.nlm.nih.gov/28199805/ and the European Association for the Study of Diabetes (EASD).
90. Cummings DE, Arterburn DE, Westbrook EO, Kuzma JN, Stewart Diabetes Care [Internet]. 2018 Dec 1 [cited 2022 Aug 9];41(12):2669–
SD, Chan CP, et al. Gastric bypass surgery vs intensive lifestyle and 701. Available from: https://pubmed.ncbi.nlm.nih.gov/30291106/
medical intervention for type 2 diabetes: the CROSSROADS randomised 104. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden
controlled trial. Diabetologia [Internet]. 2016 May 1 [cited 2022 ZT, Bush MA, et al. CONSENSUS STATEMENT BY THE
Aug 8];59(5):945. Available from: /pmc/articles/PMC4826815/ AMERICAN ASSOCIATION OF CLINICAL
91. Courcoulas AP, Belle SH, Neiberg RH, Pierson SK, Eagleton JK, ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF
Kalarchian MA, et al. Three-Year Outcomes of Bariatric Surgery vs ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2
Lifestyle Intervention for Type 2 Diabetes Mellitus Treatment: A DIABETES MANAGEMENT ALGORITHM - 2018 EXECUTIVE
Randomized Clinical Trial. JAMA Surg [Internet]. 2015 Oct 1 [cited SUMMARY. Endocr Pract [Internet]. 2018 Jan 1 [cited 2022
2022 Aug 8];150(10):931–40. Available from: https:// Aug 9];24(1):91–120. Available from: https://pubmed.ncbi.nlm.nih.gov/
pubmed.ncbi.nlm.nih.gov/26132586/ 29368965/
92. Rubino F, Nathan DM, Eckel RH, Schauer PR, Alberti KGMM, 105. Balagopal P, Kamalamma N, Patel TG, Misra R. A community-
Zimmet PZ, et al. Metabolic Surgery in the Treatment Algorithm for based diabetes prevention and management education program in a rural
Type 2 Diabetes: A Joint Statement by International Diabetes village in India. Diabetes Care [Internet]. 2008 Jun [cited 2022
Organizations. Diabetes Care [Internet]. 2016 Jun 1 [cited 2022 Aug 10];31(6):1097–104. Available from: https://
Aug 8];39(6):861–77. Available from: https://pubmed.ncbi.nlm.nih.gov/ pubmed.ncbi.nlm.nih.gov/18316397/
27222544/ 106. Baruah MP, Kalra S, Unnikrishnan AG, Raza SA, Somasundaram
93. Bhasker AG, Prasad A, Raj PP, Wadhawan R, Khaitan M, Agarwal N, John M, et al. Management of hyperglycemia in geriatric patients with
AJ, et al. OSSI (Obesity and Metabolic Surgery Society of India) diabetes mellitus: South Asian consensus guidelines. Indian J Endocrinol
Guidelines for Patient and Procedure Selection for Bariatric and Metab [Internet]. 2011 [cited 2022 Aug 9];15(2):75. Available from:
Metabolic Surgery. Obes Surg [Internet]. 2020 Jun 1 [cited 2022 /pmc/articles/PMC3125011/
Aug 8];30(6):2362–8. Available from: https://pubmed.ncbi.nlm.nih.gov/ 107. Mathews E, Thomas E, Absetz P, D’Esposito F, Aziz Z,
32125645/ Balachandran S, et al. Cultural adaptation of a peer-led lifestyle interven-
94. Vetter ML, Ritter S, Wadden TA, Sarwer DB. Comparison of tion program for diabetes prevention in India: the Kerala diabetes preven-
Bariatric Surgical Procedures for Diabetes Remission: Efficacy and tion program (K-DPP). BMC Public Health [Internet]. 2018 [cited 2022
Aug 9];17(1). Available from: https://pubmed.ncbi.nlm.nih.gov/ Available from: https://www.cambridge.org/core/journals/british-jour-

29298703/ nal-of-nutrition/article/south-asian-diets-and-insulin-resistance/
108. Weber MB, Ranjani H, Staimez LR, Anjana RM, Ali MK, Narayan B484E5A3B7776827CA5E914CC65053A1
KMV, et al. The Stepwise Approach to Diabetes Prevention: Results 122. Mohan V, Radhika G, Sathya RM, Tamil SR, Ganesan A, Sudha V.
From the D-CLIP Randomized Controlled Trial. Diabetes Care Dietary carbohydrates, glycaemic load, food groups and newly detected
[Internet]. 2016 Oct 1 [cited 2022 Aug 10];39(10):1760–7. Available type 2 diabetes among urban Asian Indian population in Chennai, India
from: https://pubmed.ncbi.nlm.nih.gov/27504014/ (Chennai Urban Rural Epidemiology Study 59). Br J Nutr [Internet].
109. Gulati S, Misra A, Tiwari R, Sharma M, Pandey RM, Prakash Yadav 2009 Nov [cited 2022 Aug 9];102(10):1498–506. Available from:
C. Effect of high-protein meal replacement on weight and cardiometabol- https://pubmed.ncbi.nlm.nih.gov/19586573/
ic profile in overweight/obese Asian Indians in North India. 123. Radhika G, van Dam RM, Sudha V, Ganesan A, Mohan V. Refined
cambridge.org [Internet]. 2017 [cited 2022 Aug 9]; Available from: grain consumption and the metabolic syndrome in urban Asian Indians
https://www.cambridge.org/core/journals/british-journal-of-nutrition/arti- (Chennai Urban Rural Epidemiology Study 57). Metabolism [Internet].
cle/effect-of-highprotein-meal-replacement-on-weight-and-cardiometa- 2009 May [cited 2022 Aug 9];58(5):675–81. Available from: https://
bolic-profile-in-overweightobese-asian-indians-in-north-india/ pubmed.ncbi.nlm.nih.gov/19375591/
44B10FA1763FB51E1FC484BBDAC56004 124. Radhika G, Sathya RM, Ganesan A, Saroja R, Vijayalakshmi P,
110. Malik VS, Sudha V, Wedick NM, Ramyabai M, Vijayalakshmi P, Sudha V, et al. Dietary profile of urban adult population in South India
Lakshmipriya N, et al. Substituting brown rice for white rice on diabetes in the context of chronic disease epidemiology (CURES-68). Public
risk factors in India: A randomised controlled trial. cambridge.org Health Nutr [Internet]. 2011 Apr [cited 2022 Aug 9];14(4):591–8.
[Internet]. 2019 [cited 2022 Aug 9]; Available from: https:// Available from: https://pubmed.ncbi.nlm.nih.gov/20701818/
www.cambridge.org/core/journals/british-journal-of-nutrition/article/ 125. Mohan V, Ruchi V, Gayathri R, Bai R, Sudha V, Anjana M, et al.
substituting-brown-rice-for-white-rice-on-diabetes-risk-factors-in-india- Slowing the diabetes epidemic in the World Health Organization South-
a - r a n d o m i z e d - c o n t r o l l e d - t r i a l / East Asia Region: the role of diet and physical activity. apps.who.int
A0778FC028F6F25D0E6A73787EECECC4 [Internet]. 2016 [cited 2022 Aug 9];5(1). Available from: https://
111. Pi-Sunyer X. The Look AHEAD Trial: A Review and Discussion of apps.who.int/iris/handle/10665/329627
Its Outcomes. Curr Nutr Rep. 2014 Dec 1;3(4):387–91. 126. Mohan V, Spiegelman D, Sudha V, Gayathri R, Hong B, Praseena
112. Myers EF, Trostler N, Varsha V, Voet H. Insights From the Diabetes K, et al. Effect of brown rice, white rice, and brown rice with legumes on
in India Nutrition Guidelines Study: Adopting Innovations Using a blood glucose and insulin responses in overweight Asian Indians: a ran-
Knowledge Transfer Model. Top Clin Nutr [Internet]. 2017 [cited 2022 domized controlled trial. Diabetes Technol Ther [Internet]. 2014 May 1
Aug 9];32(1):69. Available from: /pmc/articles/PMC5302411/ [cited 2022 Aug 9];16(5):317–25. Available from: https://
113. Gray A, Threlkeld RJ. Nutritional Recommendations for Individuals pubmed.ncbi.nlm.nih.gov/24447043/
with Diabetes. Diabetologia [Internet]. 2019 Oct 13 [cited 2022 127. Wedick NM, Sudha V, Spiegelman D, Bai MR, Malik VS,
Aug 9];54(10). Available from: https://www.ncbi.nlm.nih.gov/books/ Venkatachalam SS, et al. Study design and methods for a randomized
NBK279012/ crossover trial substituting brown rice for white rice on diabetes risk
114. Jung CH, Choi KM. Impact of High-Carbohydrate Diet on factors in India. Int J Food Sci Nutr [Internet]. 2015 [cited 2022
Metabolic Parameters in Patients with Type 2 Diabetes. Nutrients Aug 9];66(7):797–804. Available from: https://
[Internet]. 2017 Apr 1 [cited 2022 Aug 9];9(4). Available from: /pmc/ pubmed.ncbi.nlm.nih.gov/26017321/
articles/PMC5409661/ 128. Boers HM, MacAulay K, Murray P, Dobriyal R, Mela DJ,
115. Mohan V RAVM. Dietary therapy of diabetes, evaluation of the high Spreeuwenberg MAM. Efficacy of fibre additions to flatbread flour mixes
carbohydrate high fiber diet therapy. . Recent Adv Diabetes. for reducing post-meal glucose and insulin responses in healthy Indian
1983;80:657-663. subjects. British Journal of Nutrition. 2017 Feb 14;117(3):386–94.
116. Viswanathan M, Mohan V, Ramakrishna A. Long-term experience 129. Gulati S, Misra A, Pandey RM. Effects of 3 g of soluble fiber from
with high-carbohydrate high-fiber diets in Indian diabetic patients. Diab oats on lipid levels of Asian Indians - a randomized controlled, parallel
Croat. 1984;13:163–74. arm study. Lipids Health Dis [Internet]. 2017 Apr 4 [cited 2022
117. Anderson J, Care KWD, 1978 undefined. Long-term effects of high- Aug 9];16(1). Available from: https://pubmed.ncbi.nlm.nih.gov/
carbohydrate, high-fiber diets on glucose and lipid metabolism: a prelim- 28376899/
inary report on patients with diabetes. Am Diabetes Assoc [Internet]. 130. Radhika G, Sumathi C, Ganesan A, Sudha V, Jeya Kumar Henry C,
[cited 2022 Aug 9]; Available from: https://diabetesjournals.org/care/ar- Mohan V. Glycaemic index of Indian flatbreads (rotis) prepared using
ticle-abstract/1/2/77/580 whole wheat flour and ‘atta mix’-added whole wheat flour. British
118. de Natale C, Annuzzi G, Bozzetto L, Mazzarella R, Costabile G, Journal of Nutrition [Internet]. 2010 Jun [cited 2022
Ciano O, et al. Effects of a plant-based high-carbohydrate/high-fiber diet Aug 9];103(11):1642–7. Available from: https://www.cambridge.org/
versus high-monounsaturated fat/low-carbohydrate diet on postprandial core/journals/british-journal-of-nutrition/article/glycaemic-index-of-indi-
lipids in type 2 diabetic patients. Diabetes Care [Internet]. 2009 Sep 9 an-flatbreads-rotis-prepared-using-whole-wheat-flour-and-atta-
[cited 2022 Aug 9];32(12):2168–73. Available from: http://intl- m i x a d d e d - w h o l e - w h e a t - f l o u r /
care.diabetesjournals.org/cgi/content/full/32/12/2168 17DD2F55066FAF8AFEE6B3711AF582D9
119. Sylvetsky AC, Edelstein SL, Walford G, Boyko EJ, Horton ES, 131. Thondre PS, Henry CJK. High-molecular-weight barley beta-glucan
Ibebuogu UN, et al. A High-Carbohydrate, High-Fiber, Low-Fat Diet in chapatis (unleavened Indian flatbread) lowers glycemic index. Nutr
Results in Weight Loss among Adults at High Risk of Type 2 Diabetes. Res [Internet]. 2009 Jul [cited 2022 Aug 9];29(7):480–6. Available from:
J Nutr [Internet]. 2017 Nov 1 [cited 2022 Aug 9];147(11):2060. https://pubmed.ncbi.nlm.nih.gov/19700035/
Available from: /pmc/articles/PMC5657137/ 132. Gulati S, Misra A. Sugar intake, obesity, and diabetes in India.
120. Chandalia M, Garg A, Lutjohann D, von Bergmann K, Grundy SM, Nutrients [Internet]. 2014 Dec 22 [cited 2022 Aug 9];6(12):5955–74.
Brinkley LJ. Beneficial effects of high dietary fiber intake in patients with Available from: https://pubmed.ncbi.nlm.nih.gov/25533007/
type 2 diabetes mellitus. N Engl J Med [Internet]. 2000 May 11 [cited 133. Brunkwall L, Orho-Melander M. The gut microbiome as a target for
2022 Aug 9];342(19):1392–8. Available from: https:// prevention and treatment of hyperglycaemia in type 2 diabetes: from
pubmed.ncbi.nlm.nih.gov/10805824/ current human evidence to future possibilities. Diabetologia.
121. Misra A, Khurana L, … SIBJ of, 2008 undefined. South Asian diets 2017;60(6):943–51.
and insulin resistance. cambridge.org [Internet]. [cited 2022 Aug 9];
134. Dimidi E, Cox SR, Rossi M, Whelan K. Fermented Foods: with type 2 diabetes incidence in adults: A prospective assessment from
Definitions and Characteristics, Impact on the Gut Microbiota and the PREDIMED study. Clin Nutr [Internet]. 2018 Jun 1 [cited 2022
Effects on Gastrointestinal Health and Disease. Nutrients [Internet]. Aug 10];37(3):906–13. Available from: https://
2019 Aug 1 [cited 2022 Aug 21];11(8). Available from: /pmc/articles/ pubmed.ncbi.nlm.nih.gov/28392166/
PMC6723656/ 148. Narasimhan S, Nagarajan L, Vaidya R, Gunasekaran G, Rajagopal
135. Oh R, Gilani B, Uppaluri KR. Low Carbohydrate Diet. StatPearls G, Parthasarathy V, et al. Dietary fat intake and its association with risk of
[Internet]. 2022 Jul 11 [cited 2022 Aug 9]; Available from: https:// selected components of the metabolic syndrome among rural South
www.ncbi.nlm.nih.gov/books/NBK537084/ Indians. Indian J Endocrinol Metab [Internet]. 2016 Jan 1 [cited 2022
136. Sackner-Bernstein J, Kanter D, Kaul S. Dietary Intervention for Aug 10];20(1):47. Available from: /pmc/articles/PMC4743383/
Overweight and Obese Adults: Comparison of Low-Carbohydrate and 149. Nigam P, Bhatt S, Misra A, Chadha DS, Vaidya M, Dasgupta J, et al.
Low-Fat Diets. A Meta-Analysis. PLoS One [Internet]. 2015 Oct 20 [cit- Effect of a 6-month intervention with cooking oils containing a high
ed 2022 Aug 9];10(10). Available from: https:// concentration of monounsaturated fatty acids (olive and canola oils) com-
pubmed.ncbi.nlm.nih.gov/26485706/ pared with control oil in male Asian Indians with nonalcoholic fatty liver
137. Srivastava S. Low carbohydrate diet in management of obesity – A disease. Diabetes Technol Ther [Internet]. 2014 Apr 1 [cited 2022
short review. Int J Diabetes Dev Ctries. 2005;25(2):42-45. Aug 10];16(4):255–61. Available from: https://
138. Saslow LR, Mason AE, Kim S, Goldman V, Ploutz-Snyder R, pubmed.ncbi.nlm.nih.gov/24625239/
Bayandorian H, et al. An Online Intervention Comparing a Very Low- 150. Gulati S, Misra A. Abdominal obesity and type 2 diabetes in Asian
Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Indians: dietary strategies including edible oils, cooking practices and
Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A sugar intake. Eur J Clin Nutr [Internet]. 2017 Jul 1 [cited 2022
Randomized Controlled Trial. J Med Internet Res [Internet]. 2017 Feb 1 Aug 10];71(7):850–7. Available from: https://pubmed.ncbi.nlm.nih.gov/
[cited 2022 Aug 10];19(2). Available from: https:// 28612831/
pubmed.ncbi.nlm.nih.gov/28193599/ 151. Gulati S, Misra A, Sharma M. Dietary Fats and Oils in India. Curr
139. Saslow LR, Daubenmier JJ, Moskowitz JT, Kim S, Murphy EJ, Diabetes Rev [Internet]. 2017 Aug 18 [cited 2022 Aug 10];13(5).
Phinney SD, et al. Twelve-month outcomes of a randomized trial of a Available from: https://pubmed.ncbi.nlm.nih.gov/27501784/
moderate-carbohydrate versus very low-carbohydrate diet in overweight 152. Bhardwaj S, Passi SJ, Misra A, Pant KK, Anwar K, Pandey RM,
adults with type 2 diabetes mellitus or prediabetes. Nutr Diabetes et al. Effect of heating/reheating of fats/oils, as used by Asian Indians, on
[Internet]. 2017 Dec 1 [cited 2022 Aug 10];7(12). Available from: trans fatty acid formation. Food Chem. 2016 Dec 1;212:663–70.
https://pubmed.ncbi.nlm.nih.gov/29269731/ 153. Kakde S, Bhopal RS, Bhardwaj S, Misra A. Urbanized South
140. Hussain TA, Mathew TC, Dashti AA, Asfar S, Al-Zaid N, Dashti Asians’ susceptibility to coronary heart disease: The high-heat food prep-
HM. Effect of low-calorie versus low-carbohydrate ketogenic diet in type aration hypothesis. Nutrition [Internet]. 2017 Jan 1 [cited 2022
2 diabetes. Nutrition [Internet]. 2012 Oct [cited 2022 Aug 10];33:216–24. Available from: https://pubmed.ncbi.nlm.nih.gov/
Aug 10];28(10):1016–21. Available from: https:// 27776951/
pubmed.ncbi.nlm.nih.gov/22673594/ 154. Chandalia M, Garg A, Lutjohann D, von Bergmann K, Grundy SM,
141. Chandalia H, Neogi R, Insulin SM, 1992 undefined. Mechanism of Brinkley LJ. Beneficial effects of high dietary fiber intake in patients with
low glycemic index of pulses and pulse-incorporated cereal foods. type 2 diabetes mellitus. N Engl J Med. 2000 May 11;342(19):1392–8.
rssdi.in [Internet]. 1992 [cited 2022 Aug 10];12. Available from: https:// 155. Trivedi B, Maniyar K, Ctries BPIJDD, 1999 undefined. Effect of
rssdi.in/newwebsite/journal/1992_jan-mar/original_article3.pdf fibre diet (guar) on cholesterol, blood glucose and body weight. rssdi.in
142. Shobana S, Kumari SRU, Malleshi NG, Ali SZ. Glycemic response [Internet]. 1999 [cited 2022 Aug 10];19. Available from: https://rssdi.in/
of rice, wheat and finger millet based diabetic food formulations in nor- newwebsite/journal/1999_jan-mar/article5.pdf
moglycemic subjects. Int J Food Sci Nutr [Internet]. 2007 Aug [cited 156. Lattimer JM, Haub MD. Effects of dietary fiber and its components
2022 Aug 10];58(5):363–72. Available from: https:// on metabolic health. Nutrients [Internet]. 2010 [cited 2022
pubmed.ncbi.nlm.nih.gov/17558728/ Aug 10];2(12):1266–89. Available from: https://
143. Ctries JGIJDD, 2005 undefined. Trial of low glycemic diet and pubmed.ncbi.nlm.nih.gov/22254008/
acarbose therapy for control of post-prandial hyperglycemia in type 2 157. Mehta K, Kaur A. Dietary Fibre: Review. Int J Diabetes Dev Ctries.
diabetes mellitus: Preliminary report. rssdi.in [Internet]. 2005 [cited 1992;12:12–8.
2022 Aug 10];25. Available from: https://rssdi.in/newwebsite/journal/ 158. Liu AG, Most MM, Brashear MM, Johnson WD, Cefalu WT,
2005_july-sept/original_article3.pdf Greenway FL. Reducing the glycemic index or carbohydrate content of
144. Sekar V, Sundaram A, … BL… J of D, 2006 undefined. The effect mixed meals reduces postprandial glycemia and insulinemia over the
of modified pulse-carbohydrate diet on weight and HbA1C in type 2 entire day but does not affect satiety. Diabetes Care [Internet]. 2012
diabetic patients. search.ebscohost.com [Internet]. [cited 2022 Aug 10]; Aug [cited 2022 Aug 10];35(8):1633–7. Available from: https://
Available from: https://search.ebscohost.com/login.aspx?direct= pubmed.ncbi.nlm.nih.gov/22688548/
true&profile=ehost&scope=site&authtype=crawler&jrnl=09733930&A- 159. Weickert MO, Pfeiffer AFH. Impact of Dietary Fiber Consumption
N=22079421&h=KduojZVzfPrjfRVtaKGIvqmHsqt3laa7BnOWeAH on Insulin Resistance and the Prevention of Type 2 Diabetes. J Nutr
LPXcRrH1a7gWDAaI48Bkrh8JDBDGlcgquO [Internet]. 2018 Jan 1 [cited 2022 Aug 10];148(1):7–12. Available from:
RxNtPyz6OPk%2Bw%3D%3D&crl=c https://pubmed.ncbi.nlm.nih.gov/29378044/
145. Viguiliouk E, Kendall CWC, Mejia SB, Cozma AI, Ha V, Mirrahimi 160. Narayan S, Lakshmipriya N, Vaidya R, Bai M, Sudha V,
A, et al. Effect of tree nuts on glycemic control in diabetes: a systematic Krishnaswamy K, et al. Association of dietary fiber intake with serum
review and meta-analysis of randomized controlled dietary trials. PLoS total cholesterol and low density lipoprotein cholesterol levels in Urban
One [Internet]. 2014 Jul 30 [cited 2022 Aug 10];9(7). Available from: Asian-Indian adults with type 2 diabetes. Indian J Endocrinol Metab
https://pubmed.ncbi.nlm.nih.gov/25076495/ [Internet]. 2014 [cited 2022 Aug 10];18(5):624. Available from: https://
146. Green R, Milner J, Joy EJM, Agrawal S, Dangour AD. Dietary pubmed.ncbi.nlm.nih.gov/25285277/
patterns in India: a systematic review. Br J Nutr [Internet]. 2016 Jul 14 161. Yao B, Fang H, Xu W, Yan Y, Xu H, Liu Y, et al. Dietary fiber
[cited 2022 Aug 10];116(1):142–8. Available from: https:// intake and risk of type 2 diabetes: a dose-response analysis of prospective
pubmed.ncbi.nlm.nih.gov/27146890/ studies. Eur J Epidemiol [Internet]. 2014 [cited 2022 Aug 10];29(2):79–
147. Becerra-Tomás N, Díaz-López A, Rosique-Esteban N, Ros E, Buil- 88. Available from: https://pubmed.ncbi.nlm.nih.gov/24389767/
Cosiales P, Corella D, et al. Legume consumption is inversely associated
162. Emadian A, Thompson JL. A Mixed-Methods Examination of 175. Abdi S, Sadiya A, Ali S, Varghese S, Abusnana S. Behavioural
Physical Activity and Sedentary Time in Overweight and Obese South Lifestyle Intervention Study (BLIS) in patients with type 2 diabetes in
Asian Men Living in the United Kingdom. Int J Environ Res Public the United Arab Emirates: A randomized controlled trial. BMC Nutr
Health [Internet]. 2017 Apr 1 [cited 2022 Aug 10];14(4). Available from: [Internet]. 2015 Jul 30 [cited 2022 Aug 10];1(1):1–9. Available from:
https://pubmed.ncbi.nlm.nih.gov/28346386/ https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-015-0028-4
163. Reed JL, Pipe AL. The talk test: a useful tool for prescribing and 176. Wang J, Cai C, Padhye N, Orlander P, Zare M. A Behavioral
monitoring exercise intensity. Curr Opin Cardiol [Internet]. 2014 [cited Lifestyle Intervention Enhanced With Multiple-Behavior Self-
2022 Aug 21];29(5):475–80. Available from: https:// Monitoring Using Mobile and Connected Tools for Underserved
pubmed.ncbi.nlm.nih.gov/25010379/ Individuals With Type 2 Diabetes and Comorbid Overweight or
164. Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT, Obesity: Pilot Comparative Effectiveness Trial. JMIR Mhealth Uhealth
et al. Effect of physical inactivity on major non-communicable diseases [Internet]. 2018 Apr 1 [cited 2022 Aug 10];6(4). Available from: https://
worldwide: an analysis of burden of disease and life expectancy. Lancet pubmed.ncbi.nlm.nih.gov/29636320/
[Internet]. 2012 [cited 2022 Aug 10];380(9838):219–29. Available from: 177. Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD,
https://pubmed.ncbi.nlm.nih.gov/22818936/ Vijay V. The Indian Diabetes Prevention Programme shows that lifestyle
165. Church TS, Blair SN, Cocreham S, Johannsen N, Johnson W, modification and metformin prevent type 2 diabetes in Asian Indian sub-
Kramer K, et al. Effects of Aerobic and Resistance Training on jects with impaired glucose tolerance (IDPP-1). Diabetologia [Internet].
Hemoglobin A 1c Levels in Patients With Type 2 Diabetes. JAMA. 2006 Feb [cited 2022 Aug 10];49(2):289–97. Available from: https://
2010 Nov 24;304(20):2253. pubmed.ncbi.nlm.nih.gov/16391903/
166. Boulé NG, Kenny GP, Haddad E, Wells GA, Sigal RJ. Meta- 178. Baker MK, Simpson K, Lloyd B, Bauman AE, Singh MAF.
analysis of the effect of structured exercise training on cardiorespiratory Behavioral strategies in diabetes prevention programs: a systematic re-
fitness in Type 2 diabetes mellitus. Diabetologia [Internet]. 2003 Aug 1 view of randomized controlled trials. Diabetes Res Clin Pract [Internet].
[cited 2022 Aug 10];46(8):1071–81. Available from: https:// 2011 Jan [cited 2022 Aug 10];91(1):1–12. Available from: https://
167. Iliodromiti S, Ghouri N, Celis-Morales CA, Sattar N, Lumsden MA, 179. Lin CL, Huang LC, Chang YT, Chen RY, Yang SH, Chang YT;,
Gill JMR. Should Physical Activity Recommendations for South Asian et al. Effectiveness of Health Coaching in Diabetes Control and Lifestyle
Adults Be Ethnicity-Specific? Evidence from a Cross-Sectional Study of Improvement: A Randomized-Controlled Trial. Nutrients 2021, Vol 13,
South Asian and White European Men and Women. PLoS One [Internet]. Page 3878 [Internet]. 2021 Oct 29 [cited 2022 Aug 9];13(11):3878.
2016 Aug 1 [cited 2022 Aug 10];11(8). Available from: https:// Available from: https://www.mdpi.com/2072-6643/13/11/3878/htm
pubmed.ncbi.nlm.nih.gov/27529339/ 180. Lam WY, Fresco P. Medication Adherence Measures: An
168. Hameed UA, Manzar D, Raza S, Shareef MY, Hussain ME. Overview. Biomed Res Int. 2015;2015:217047.
Resistance Training Leads to Clinically Meaningful Improvements in 181. Middleton KR, Anton SD, Perri MG. Long-Term Adherence to
Control of Glycemia and Muscular Strength in Untrained Middle-aged Health Behavior Change. Am J Lifestyle Med [Internet]. 2013 Nov [cited
Patients with type 2 Diabetes Mellitus. N Am J Med Sci [Internet]. 2012 2022 Aug 10];7(6):395–404. Available from: https://
[cited 2022 Aug 10];4(8):336–43. Available from: https:// pubmed.ncbi.nlm.nih.gov/27547170/
pubmed.ncbi.nlm.nih.gov/22912941/ 182. Basak Cinar A, Schou L. Health promotion for patients with diabe-
169. Hou Y, Lin L, Li W, Qiu J, Zhang Y, Wang X. Effect of combined tes: health coaching or formal health education? Int Dent J [Internet].
training versus aerobic training alone on glucose control and risk factors 2014 Feb [cited 2022 Aug 9];64(1):20–8. Available from: https://
for complications in type 2 diabetic patients: a meta-analysis. Int J pubmed.ncbi.nlm.nih.gov/24117102/
Diabetes Dev Ctries. 2015 Nov 1;35(4):524–32. 183. Bleich SN. Updated USPSTF Recommendations for Behavioral
170. Aylin K, Arzu D, Sabri S, Handan TE, Ridvan A. The effect of Counseling Interventions. JAMA Intern Med. 2022 Jul 26;
combined resistance and home-based walking exercise in type 2 diabetes 184. Antza C, Kostopoulos G, Mostafa S, Nirantharakumar K, Tahrani A.
patients. Int J Diabetes Dev Ctries [Internet]. 2009 [cited 2022 The links between sleep duration, obesity and type 2 diabetes mellitus. J
Aug 10];29(4):159–65. Available from: https:// Endocrinol. 2021;252(2):125–41.
pubmed.ncbi.nlm.nih.gov/20336198/ 185. Sharma VK, Singh TG. Chronic Stress and Diabetes Mellitus:
171. Kalyani RR, Cannon CP, Cherrington AL, Coustan DR, de Boer IH, Interwoven Pathologies. Curr Diabetes Rev. 2020 Jun 14;16(6):546–56.
Feldman H, et al. Professional Practice Committee: Standards of Medical 186. Siddiqui A, Madhu S v., Sharma SB, Desai NG. Endocrine stress
Care in Diabetes—2018. Diabetes Care [Internet]. 2018 Jan 1 [cited 2022 responses and risk of type 2 diabetes mellitus. Stress. 2015 Sep
Aug 10];41(Supplement_1):S3–S3. Available from: https:// 3;18(5):498–506.
diabetesjournals.org/care/article/41/Supplement_1/S3/30078/ 187. Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to
Professional-Practice-Committee-Standards-of type 2 diabetes and recent advances in the treatment and prevention. Int J
172. Misra A, Nigam P, Hills AP, Chadha DS, Sharma V, Deepak KK, Med Sci [Internet]. 2014 [cited 2022 Aug 13];11(11):1185–200.
et al. Consensus physical activity guidelines for Asian Indians. Diabetes Available from: https://pubmed.ncbi.nlm.nih.gov/25249787/
Technol Ther [Internet]. 2012 Jan 1 [cited 2022 Aug 10];14(1):83–98. 188. Defronzo RA. From the Triumvirate to the Ominous Octet: A New
Available from: https://pubmed.ncbi.nlm.nih.gov/21988275/ Paradigm for the Treatment of Type 2 Diabetes Mellitus. Diabetes
173. Spahn JM, Reeves RS, Keim KS, Laquatra I, Kellogg M, Jortberg B, [Internet]. 2009 Apr [cited 2022 Aug 13];58(4):773. Available from:
et al. State of the evidence regarding behavior change theories and strat- /pmc/articles/PMC2661582/
egies in nutrition counseling to facilitate health and food behavior change. 189. Wells JCK, Pomeroy E, Walimbe SR, Popkin BM, Yajnik CS. The
J Am Diet Assoc [Internet]. 2010 Jun [cited 2022 Aug 10];110(6):879– Elevated Susceptibility to Diabetes in India: An Evolutionary
91. Available from: https://pubmed.ncbi.nlm.nih.gov/20497777/ Perspective. Front Public Health [Internet]. 2016 Jul 7 [cited 2022
174. Vermunt PWA, Milder IEJ, Wielaard F, Baan CA, Schelfhout JDM, Aug 13];4:1. Available from: /pmc/articles/PMC4935697/
Westert GP, et al. Behavior change in a lifestyle intervention for type 2 190. Mehta SR, Kashyap AS, Das S. Diabetes Mellitus in India: The
diabetes prevention in Dutch primary care: Opportunities for intervention Modern Scourge. Med J Armed Forces India [Internet]. 2009 [cited
content. BMC Fam Pract [Internet]. 2013 Jun 7 [cited 2022 2022 Aug 13];65(1):50–4. Available from: https://
Aug 10];14(1):1–8. Available from: https:// pubmed.ncbi.nlm.nih.gov/27408191/
bmcprimcare.biomedcentral.com/articles/10.1186/1471-2296-14-78 191. Mohan V. Why are Indians more prone to diabetes? J Assoc
Physicians India. 2004 Jun;52:468–74.
192. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden 2018. A Consensus Report by the American Diabetes Association (ADA)
ZT, Bush MA, et al. CONSENSUS STATEMENT BY THE and the European Association for the Study of Diabetes (EASD).
AMERICAN ASSOCIATION OF CLINICAL Diabetes Care [Internet]. 2018 Dec 1 [cited 2022 Aug 13];41(12):2669–
ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF 701. Available from: https://pubmed.ncbi.nlm.nih.gov/30291106/
ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 207. Guardado-Mendoza R, Prioletta A, Jiménez-Ceja LM, Sosale A,
DIABETES MANAGEMENT ALGORITHM - 2019 EXECUTIVE Folli F. The role of nateglinide and repaglinide, derivatives of
SUMMARY. Endocr Pract [Internet]. 2019 Jan 1 [cited 2022 meglitinide, in the treatment of type 2 diabetes mellitus. Arch Med Sci
Aug 13];25(1):69–100. Available from: https:// [Internet]. 2013 Oct 10 [cited 2022 Aug 13];9(5):936. Available from:
pubmed.ncbi.nlm.nih.gov/30742570/ /pmc/articles/PMC3832818/
193. Thrasher J. Pharmacologic Management of Type 2 Diabetes 208. Camp HS. Thiazolidinediones in diabetes: current status and future
Mellitus: Available Therapies. Am J Med [Internet]. 2017 Jun 1 [cited outlook. Curr Opin Investig Drugs. 2003 Apr;4(4):406–11.
2022 Aug 13];130(6S):S4–17. Available from: https:// 209. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones
pubmed.ncbi.nlm.nih.gov/28526182/ NP, et al. Glycemic durability of rosiglitazone, metformin, or glyburide
194. Holman R. Metformin as first choice in oral diabetes treatment: the monotherapy. N Engl J Med [Internet]. 2006 Dec 7 [cited 2022
UKPDS experience. Journ Annu Diabetol Hotel Dieu. 2007;13–20. Aug 13];355(23):2427–43. Available from: https://
195. Ripsin CM, Kang H, Urban RJ. Management of blood glucose in pubmed.ncbi.nlm.nih.gov/17145742/
type 2 diabetes mellitus. Am Fam Physician. 2009 Jan 1;79(1):29–36. 210. Nissen SE, Wolski K. Effect of Rosiglitazone on the Risk of
196. Rena G, Hardie DG, Pearson ER. The mechanisms of action of Myocardial Infarction and Death from Cardiovascular Causes. https://
metformin. Diabetologia [Internet]. 2017 Sep 1 [cited 2022 doi.org/101056/NEJMoa072761 [Internet]. 2007 Jun 14 [cited 2022
Aug 13];60(9):1577–85. Available from: https:// Aug 13];356(24):2457–71. Available from: https://www.nejm.org/doi/
pubmed.ncbi.nlm.nih.gov/28776086/ full/10.1056/nejmoa072761
197. Turner R. Effect of intensive blood-glucose control with metformin 211. Defronzo RA, Mehta RJ, Schnure JJ. Pleiotropic effects of thiazol-
on complications in overweight patients with type 2 diabetes (UKPDS idinediones: implications for the treatment of patients with type 2 diabetes
34). Lancet [Internet]. 1998 Sep 12 [cited 2022 Aug 13];352(9131):854– mellitus. Hosp Pract (1995) [Internet]. 2013 [cited 2022
65. Available from: http://www.thelancet.com/article/ Aug 13];41(2):132–47. Available from: https://
S0140673698070378/fulltext pubmed.ncbi.nlm.nih.gov/23680744/
198. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10- 212. Dormandy JA, Charbonnel B, Eckland DJA, Erdmann E, Massi-
year follow-up of intensive glucose control in type 2 diabetes. N Engl J Benedetti M, Moules IK, et al. Secondary prevention of macrovascular
Med [Internet]. 2008 Oct 9 [cited 2022 Aug 13];359(15):1577–89. events in patients with type 2 diabetes in the PROactive Study
Available from: https://pubmed.ncbi.nlm.nih.gov/18784090/ (PROspective pioglitAzone Clinical Trial In macroVascular Events): a
199. Rojas LBA, Gomes MB. Metformin: an old but still the best treat- randomised controlled trial. Lancet [Internet]. 2005 Oct 8 [cited 2022
ment for type 2 diabetes. Diabetol Metab Syndr [Internet]. 2013 [cited Aug 13];366(9493):1279–89. Available from: https://
2022 Aug 13];5(1). Available from: https://pubmed.ncbi.nlm.nih.gov/ pubmed.ncbi.nlm.nih.gov/16214598/
23415113/ 213. Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE,
200. Kalra S, Aamir AH, Raza A, Das AK, Khan AKA, Shrestha D, et al. Gorman M, et al. Pioglitazone after Ischemic Stroke or Transient
Place of sulfonylureas in the management of type 2 diabetes mellitus in Ischemic Attack. N Engl J Med [Internet]. 2016 Apr 7 [cited 2022
South Asia: A consensus statement. Indian J Endocrinol Metab [Internet]. Aug 13];374(14):1321–31. Available from: https://
2015 Sep 1 [cited 2022 Aug 13];19(5):577–96. Available from: https:// pubmed.ncbi.nlm.nih.gov/26886418/
pubmed.ncbi.nlm.nih.gov/26425465/ 214. Spence JD, Viscoli CM, Inzucchi SE, Dearborn-Tomazos J, Ford
201. Sola D, Rossi L, Schianca GPC, Maffioli P, Bigliocca M, Mella R, GA, Gorman M, et al. Pioglitazone Therapy in Patients With Stroke and
et al. Sulfonylureas and their use in clinical practice. Arch Med Sci Prediabetes: A Post Hoc Analysis of the IRIS Randomized Clinical Trial.
[Internet]. 2015 Aug 1 [cited 2022 Aug 13];11(4):840–8. Available from: JAMA Neurol [Internet]. 2019 May 1 [cited 2022 Aug 13];76(5):526–35.
https://pubmed.ncbi.nlm.nih.gov/26322096/ Available from: https://pubmed.ncbi.nlm.nih.gov/30734043/
202. Weintraub NL. Impaired hypoxic coronary vasodilation and ATP- 215. Lewis JD, Ferrara A, Peng T, Hedderson M, Bilker WB,
sensitive potassium channel function: a manifestation of diabetic micro- Quesenberry CP, et al. Risk of bladder cancer among diabetic patients
angiopathy in humans? Circ Res [Internet]. 2003 Feb 7 [cited 2022 treated with pioglitazone: interim report of a longitudinal cohort study.
Aug 13];92(2):127–9. Available from: https://pubmed.ncbi.nlm.nih.gov/ Diabetes Care [Internet]. 2011 Apr [cited 2022 Aug 13];34(4):916–22.
12574137/ Available from: https://pubmed.ncbi.nlm.nih.gov/21447663/
203. Garratt KN, Brady PA, Hassinger NL, Grill DE, Terzic A, Holmes 216. Pai SA, Kshirsagar NA. Pioglitazone utilization, efficacy & safety in
DR. Sulfonylurea drugs increase early mortality in patients with diabetes Indian type 2 diabetic patients: A systematic review & comparison with
mellitus after direct angioplasty for acute myocardial infarction. J Am European Medicines Agency Assessment Report. Indian J Med Res
Coll Cardiol [Internet]. 1999 Jan [cited 2022 Aug 13];33(1):119–24. [Internet]. 2016 Nov 1 [cited 2022 Aug 13];144(5):672–81. Available
Available from: https://pubmed.ncbi.nlm.nih.gov/9935017/ from: https://pubmed.ncbi.nlm.nih.gov/28361819/
204. Varvaki Rados D, Catani Pinto L, Reck Remonti L, Bauermann 217. Cahn A, Raz I. Emerging gliptins for type 2 diabetes. Expert Opin
Leitão C, Gross JL. The Association between Sulfonylurea Use and Emerg Drugs [Internet]. 2013 Jun [cited 2022 Aug 13];18(2):245–58.
All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Available from: https://pubmed.ncbi.nlm.nih.gov/23725569/
Sequential Analysis of Randomized Clinical Trials. PLoS Med. 2016 218. Pathak R, Bridgeman MB. Dipeptidyl Peptidase-4 (DPP-4)
Apr;13(4):e1001992. Inhibitors In the Management of Diabetes. Pharmacy and Therapeutics
205. Kalra S, Bahendeka S, Sahay R, Ghosh S, Md F, Orabi A, et al. [Internet]. 2010 Sep [cited 2022 Aug 13];35(9):509. Available from:
Consensus Recommendations on Sulfonylurea and Sulfonylurea /pmc/articles/PMC2957740/
Combinations in the Management of Type 2 Diabetes Mellitus - 219. Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H.
International Task Force. Indian J Endocrinol Metab [Internet]. 2018 Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as
Jan 1 [cited 2022 Aug 13];22(1):132–57. Available from: https:// monotherapy in patients with type 2 diabetes mellitus. Diabetologia
pubmed.ncbi.nlm.nih.gov/29535952/ [Internet]. 2006 [cited 2022 Aug 13];49(11):2564–71. Available from:
206. Davies MJ, D’Alessio DA, Fradkin J, Kernan WN, Mathieu C, https://pubmed.ncbi.nlm.nih.gov/17001471/
Mingrone G, et al. Management of Hyperglycemia in Type 2 Diabetes,
220. Ahrén B. Use of DPP-4 inhibitors in type 2 diabetes: focus on 234. Rosenstock J, Aggarwal N, Polidori D, Zhao Y, Arbit D, Usiskin K,
sitagliptin. Diabetes Metab Syndr Obes [Internet]. 2010 Mar [cited et al. Dose-ranging effects of canagliflozin, a sodium-glucose
2022 Aug 13];3:31. Available from: /pmc/articles/PMC3047982/ cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2
221. Stein SA, Lamos EM, Davis SN. A review of the efficacy and safety diabetes. Diabetes Care [Internet]. 2012 Jun [cited 2022
of oral antidiabetic drugs. Expert Opin Drug Saf [Internet]. 2013 Mar Aug 13];35(6):1232–8. Available from: https://
pubmed.ncbi.nlm.nih.gov/23241069/ 235. Baker WL, Buckley LF, Kelly MS, Bucheit JD, Parod ED, Brown R,
222. Wu S, Hopper I, Skiba M, Krum H. Dipeptidyl peptidase-4 inhibi- et al. Effects of Sodium-Glucose Cotransporter 2 Inhibitors on 24-Hour
tors and cardiovascular outcomes: meta-analysis of randomized clinical Ambulatory Blood Pressure: A Systematic Review and Meta-Analysis. J
trials with 55,141 participants. Cardiovasc Ther [Internet]. 2014 [cited Am Heart Assoc [Internet]. 2017 May 1 [cited 2022 Aug 13];6(5).
2022 Aug 13];32(4):147–58. Available from: https:// Available from: https://pubmed.ncbi.nlm.nih.gov/28522675/
pubmed.ncbi.nlm.nih.gov/24750644/ 236. Nyirjesy P, Zhao Y, Ways K, Usiskin K. Evaluation of vulvovaginal
223. Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, symptoms and Candida colonization in women with type 2 diabetes
et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 mellitus treated with canagliflozin, a sodium glucose co-transporter 2
Diabetes. New England Journal of Medicine [Internet]. 2015 Jul 16 [cited inhibitor. Curr Med Res Opin [Internet]. 2012 Jul [cited 2022
2022 Aug 13];373(3):232–42. Available from: https://www.nejm.org/ Aug 13];28(7):1173–8. Available from: https://
doi/full/10.1056/nejmoa1501352 pubmed.ncbi.nlm.nih.gov/22632452/
224. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, 237. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapa-
Hirshberg B, et al. Saxagliptin and cardiovascular outcomes in patients gliflozin in patients with type 2 diabetes who have inadequate glycaemic
with type 2 diabetes mellitus. N Engl J Med [Internet]. 2013 Oct 3 [cited control with metformin: a randomised, double-blind, placebo-controlled
2022 Aug 12];369(14):1317–26. Available from: https:// trial. Lancet [Internet]. 2010 [cited 2022 Aug 13];375(9733):2223–33.
pubmed.ncbi.nlm.nih.gov/23992601/ Available from: https://pubmed.ncbi.nlm.nih.gov/20609968/
225. Zannad F, Cannon CP, Cushman WC, Bakris GL, Menon V, Perez 238. Grempler R, Thomas L, Eckhardt M, Himmelsbach F, Sauer A,
AT, et al. Heart failure and mortality outcomes in patients with type 2 Sharp DE, et al. Empagliflozin, a novel selective sodium glucose
diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, cotransporter-2 (SGLT-2) inhibitor: Characterisation and comparison
randomised, double-blind trial. Lancet [Internet]. 2015 May 23 [cited with other SGLT-2 inhibitors. Diabetes Obes Metab. 2012;14(1):83–90.
2022 Aug 13];385(9982):2067–76. Available from: https:// 239. Stenlöf K, Cefalu WT, Kim KA, Alba M, Usiskin K, Tong C, et al.
pubmed.ncbi.nlm.nih.gov/25765696/ Efficacy and safety of canagliflozin monotherapy in subjects with type 2
226. FDA Drug Safety Communication: FDA adds warnings about heart diabetes mellitus inadequately controlled with diet and exercise. Diabetes
failure risk to labels of type 2 diabetes medicines containing saxagliptin Obes Metab [Internet]. 2013 [cited 2022 Aug 13];15(4):372–82.
and alogliptin | FDA [Internet]. [cited 2022 Aug 13]. Available from: Available from: https://pubmed.ncbi.nlm.nih.gov/23279307/
https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety- 240. Yoon KH, Nishimura R, Lee J, Crowe S, Salsali A, Hach T, et al.
communication-fda-adds-warnings-about-heart-failure-risk-labels-type- Efficacy and safety of empagliflozin in patients with type 2 diabetes from
2-diabetes Asian countries: pooled data from four phase III trials. Diabetes Obes
227. Rosenstock J, Perkovic V, Johansen OE, Cooper ME, Kahn SE, Metab [Internet]. 2016 Oct 1 [cited 2022 Aug 13];18(10):1045–9.
Marx N, et al. Effect of Linagliptin vs Placebo on Major Cardiovascular Available from: https://pubmed.ncbi.nlm.nih.gov/27265507/
Events in Adults With Type 2 Diabetes and High Cardiovascular and 241. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL,
Renal Risk: The CARMELINA Randomized Clinical Trial. JAMA Charytan DM, et al. Canagliflozin and Renal Outcomes in Type 2
[Internet]. 2019 Jan 1 [cited 2022 Aug 13];321(1):69–79. Available from: Diabetes and Nephropathy. New England Journal of Medicine
https://pubmed.ncbi.nlm.nih.gov/30418475/ [Internet]. 2019 Jun 13 [cited 2022 Aug 13];380(24):2295–306.
228. Boehringer Ingelheim and Lilly’s CAROLINA® cardiovascular Available from: https://www.nejm.org/doi/full/10.1056/nejmoa1811744
outcome trial for Trajenta® meets primary endpoint of non-inferiority 242. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod
compared to glimepiride [Internet]. [cited 2022 Aug 13]. Available from: MN, Martinez FA, et al. Dapagliflozin in Patients with Heart Failure
https://www.businesswireindia.com/boehringer-ingelheim-and-lilly-car- and Reduced Ejection Fraction. https://doi.org/101056/
olina-cardiovascular-outcome-trial-for-trajenta-meets-primary-endpoint- NEJMoa1911303 [Internet]. 2019 Sep 19 [cited 2022
of-non-inferiority-compared-to-glimepiride-61931.html Aug 13];381(21):1995–2008. Available from: https://www.nejm.org/
229. DeFronzo RA, Davidson JA, del Prato S. The role of the kidneys in doi/full/10.1056/NEJMoa1911303
glucose homeostasis: a new path towards normalizing glycaemia. 243. Bischoff H. Pharmacology of alpha-glucosidase inhibition. Eur J
Diabetes Obes Metab [Internet]. 2012 [cited 2022 Aug 13];14(1):5–14. Clin Invest. 1994 Aug;24 Suppl 3:3–10.
Available from: https://pubmed.ncbi.nlm.nih.gov/21955459/ 244. Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with
230. Singh AK, Unnikrishnan AG, Zargar AH, Kumar A, Das AK, Saboo acarbose, metformin, or placebo in dietary-treated NIDDM patients: The
B, et al. Evidence-Based Consensus on Positioning of SGLT2i in Type 2 essen-II study. American Journal of Medicine [Internet]. 1997 Dec [cited
Diabetes Mellitus in Indians. Diabetes Ther [Internet]. 2019 Apr 1 [cited 2022 Aug 13];103(6):483–90. Available from: https://
2022 Aug 13];10(2):393–428. Available from: https:// pubmed.ncbi.nlm.nih.gov/9428831/
pubmed.ncbi.nlm.nih.gov/30706366/ 245. Halimi S, le Berre MA, Grangé V. Efficacy and safety of acarbose
231. Markham A. Remogliflozin Etabonate: First Global Approval. add-on therapy in the treatment of overweight patients with Type 2 dia-
Drugs [Internet]. 2019 Jul 1 [cited 2022 Aug 13];79(10):1157–61. betes inadequately controlled with metformin: a double-blind, placebo-
Available from: https://pubmed.ncbi.nlm.nih.gov/31201711/ controlled study. Diabetes Res Clin Pract [Internet]. 2000 Sep [cited 2022
232. B Z, C W, JM L, D F, E B, S H, et al. Empagliflozin, Cardiovascular Aug 13];50(1):49–56. Available from: https://pubmed.ncbi.nlm.nih.gov/
Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med [Internet]. 10936668/
2015 [cited 2022 Aug 12];373(22):17–8. Available from: https:// 246. Rodbard HW, Rosenstock J, Canani LH, Deerochanawong C,
pubmed.ncbi.nlm.nih.gov/26378978/ Gumprecht J, Lindberg SØ, et al. Oral Semaglutide Versus
233. Neal B, Perkovic V, Matthews DR. Canagliflozin and Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on
Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. Metformi n: The P IONEER 2 Trial. D iabetes Care. 2019
2017;377(21):2099. Dec 1;42(12):2272–81.
247. Rosenstock J, Allison D, Birkenfeld AL, Blicher TM, Deenadayalan 260. Edridge CL, Dunkley AJ, Bodicoat DH, Rose TC, Gray LJ, Davies
S, Jacobsen JB, et al. Effect of Additional Oral Semaglutide vs Sitagliptin MJ, et al. Prevalence and Incidence of Hypoglycaemia in 532,542 People
on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled with Type 2 Diabetes on Oral Therapies and Insulin: A Systematic
With Metformin Alone or With Sulfonylurea. JAMA. 2019 Review and Meta-Analysis of Population Based Studies. PLoS One
Apr 16;321(15):1466. [Internet]. 2015 Jun 10 [cited 2022 Aug 11];10(6). Available from:
248. Rosenstock J, Allison D, Birkenfeld AL, Blicher TM, Deenadayalan https://pubmed.ncbi.nlm.nih.gov/26061690/
S, Jacobsen JB, et al. Effect of Additional Oral Semaglutide vs Sitagliptin 261. Chandalia HB, Lamba PS, Chandalia SH, Singh DK, Modi S v.,
on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled Shaikh SA. Weight gain in type 2 diabetics with different treatment mo-
With Metformin Alone or With Sulfonylurea: The PIONEER 3 dalities. Metab Syndr Relat Disord [Internet]. 2005 Jun [cited 2022
Randomized Clinical Trial. JAMA [Internet]. 2019 Apr 16 [cited 2022 Aug 11];3(2):130–6. Available from: https://pubmed.ncbi.nlm.nih.gov/
Aug 13];321(15):1466–80. Available from: https:// 18370720/
pubmed.ncbi.nlm.nih.gov/30903796/ 262. Vos RC, van Avendonk MJP, Jansen H, Goudswaard AN, van den
249. Pratley R, Amod A, Hoff ST, Kadowaki T, Lingvay I, Nauck M, Donk M, Gorter K, et al. Insulin monotherapy compared with the addition
et al. Oral semaglutide versus subcutaneous liraglutide and placebo in of oral glucose-lowering agents to insulin for people with type 2 diabetes
type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. already on insulin therapy and inadequate glycaemic control. Cochrane
Lancet [Internet]. 2019 Jul 6 [cited 2022 Aug 13];394(10192):39–50. Database Syst Rev [Internet]. 2016 Sep 18 [cited 2022 Aug 11];9(9).
Available from: https://pubmed.ncbi.nlm.nih.gov/31186120/ Available from: https://pubmed.ncbi.nlm.nih.gov/27640062/
250. Kalra S, Das S, Zargar A. A review of oral semaglutide available 263. Kalra S, Ghosal S, Shah P. Consensus on Bridges for Barriers to
evidence: A new era of management of diabetes with peptide in a pill Insulin Therapy. J Assoc Physicians India. 2017 Mar;65(3 Suppl):23–30.
form. Indian J Endocrinol Metab [Internet]. 2022 [cited 2022 264. International Diabetes Federation Guideline Development Group.
Aug 13];26(2):98. Available from: https://journals.lww.com/indjem/ Global guideline for type 2 diabetes. Diabetes Res Clin Pract. 2014
F u l l t e x t / 2 0 2 2 / 0 4 0 0 0 / Apr;104(1):1–52.
A_Review_of_Oral_Semaglutide_Available_Evidence__A.2.aspx 265. Kalra S, Gupta Y. Insulin initiation: bringing objectivity to choice. J
251. Cavaiola TS, Pettus JH. Management Of Type 2 Diabetes: Selecting Diabetes Metab Disord [Internet]. 2015 Mar 25 [cited 2022
Amongst Available Pharmacological Agents. 2000. Aug 11];14(1). Available from: /pmc/articles/PMC4396869/
252. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of 266. Chawla R, Makkar BM, Aggarwal & S, Bajaj & S, Das AK, Ghosh
Medical Care in Diabetes-2019. Diabetes Care [Internet]. 2019 Jan 1 & S, et al. RSSDI consensus recommendations on insulin therapy in the
[cited 2022 Aug 11];42(Suppl 1):S90–102. Available from: https:// management of diabetes. [cited 2022 Sep 15]; Available from: https://
pubmed.ncbi.nlm.nih.gov/30559235/ doi.org/10.1007/s13410-019-00783-6
253. Baruah MP, Kalra S, Bose S, Deka J. An Audit of Insulin Usage and 267. Kim W, Egan JM. The Role of Incretins in Glucose Homeostasis and
Insulin Injection Practices in a Large Indian Cohort. Indian J Endocrinol Diabetes Treatment. Pharmacol Rev [Internet]. 2008 Dec [cited 2022
Metab [Internet]. 2017 May 1 [cited 2022 Aug 11];21(3):443–52. Aug 11];60(4):470. Available from: /pmc/articles/PMC2696340/
Available from: https://pubmed.ncbi.nlm.nih.gov/28553603/ 268. Bentley-Lewis R, Aguilar D, Riddle MC, Claggett B, Diaz R,
254. Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Dickstein K, et al. Rationale, design, and baseline characteristics in
Zimmerman RS, Bailey TS, et al. American association of clinical endo- Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term
crinologists and American college of endocrinology - Clinical practice cardiovascular end point trial of lixisenatide versus placebo. Am Heart J
guidelines for developing a diabetes mellitus comprehensive care plan - [Internet]. 2015 May 1 [cited 2022 Aug 11];169(5):631-638.e7.
2015 -. Endocr ine P rac ti ce [Inte rnet] . 2015 [c it ed 2 022 Available from: https://pubmed.ncbi.nlm.nih.gov/25965710/
Aug 11];21(4):413–37. Available from: https:// 269. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann
pubmed.ncbi.nlm.nih.gov/25869408/ JFE, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type
255. JM L, S G, P C, MD D, DM N. Retinopathy and nephropathy in 2 diabetes. Drug Ther Bull [Internet]. 2016 Jul 28 [cited 2022
patients with type 1 diabetes four years after a trial of intensive therapy. N Aug 11];54(9):101. Available from: https://www.nejm.org/doi/full/
Engl J Med [Internet]. 2000 Feb 10 [cited 2022 Aug 11];342(6):381–9. 10.1056/nejmoa1603827
Available from: https://pubmed.ncbi.nlm.nih.gov/10666428/ 270. IDF Diabetes Atlas | Tenth Edition [Internet]. [cited 2022 Aug 11].
256. Raccah D. Basal insulin treatment intensification in patients with Available from: https://diabetesatlas.org/
type 2 diabetes mellitus: A comprehensive systematic review of current 271. Bennett WL, Maruthur NM, Singh S, Segal JB, Wilson LM,
options. Diabetes Metab [Internet]. 2017 Apr 1 [cited 2022 Chatterjee R, et al. Comparative Effectiveness and Safety of
Aug 11];43(2):110–24. Available from: https:// Medications for Type 2 Diabetes: An Update Including New Drugs and
pubmed.ncbi.nlm.nih.gov/28169086/ 2-Drug Combinations. Ann Intern Med. 2011 May 3;154(9):602.
257. Kalra S, Baruah MP, Sahay RK, Unnikrishnan AG, Uppal S, 272. Kesavadev J, Rajput R, John M, Annamalai AK, Rao P v.
Adetunji O. Glucagon-like peptide-1 receptor agonists in the treatment Consensus statement on Choice of Insulin Therapy in Type 2 diabetes.
of type 2 diabetes: Past, present, and future. Indian J Endocrinol Metab 2016.
[Internet]. 2016 Mar 1 [cited 2022 Aug 11];20(2):254–67. Available 273. IDF_DA_8e-EN-final.
from: https://pubmed.ncbi.nlm.nih.gov/27042424/ 274. Barnett AH, Huisman H, Jones R, von Eynatten M, Patel S, Woerle
258. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, HJ. Linagliptin for patients aged 70 years or older with type 2 diabetes
Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a inadequately controlled with common antidiabetes treatments: a
patient-centered approach: position statement of the American Diabetes randomised, double-blind, placebo-controlled trial. The Lancet. 2013
Association (ADA) and the European Association for the Study of Oct;382(9902):1413–23.
Diabetes (EASD). Diabetes Care [Internet]. 2012 Jun 1 [cited 2022 275. Chien MN, Lee CC, Chen WC, Liu SC, Leung CH, Wang CH.
Aug 11];35(6):1364–79. Available from: https:// Effect of Sitagliptin as Add-on Therapy in Elderly Type 2 Diabetes
pubmed.ncbi.nlm.nih.gov/22517736/ Patients With Inadequate Glycemic Control in Taiwan. Int J Gerontol.
259. Ismail-Beigi F, Moghissi E, Tiktin M, Hirsch B, Inzucchi SE, 2011 Jun;5(2):103–6.
Genuth S. Individualizing glycemic targets in type 2 diabetes mellitus: 276. Strain WD, Agarwal AS, Paldánius PM. Individualizing treatment
implications of recent clinical trials. Ann Intern Med [Internet]. 2011 targets for elderly patients with type 2 diabetes: factors influencing clin-
[cited 2022 Aug 11];154(8):554–9. Available from: https:// ical decision making in the 24-week, randomized INTERVAL study.
pubmed.ncbi.nlm.nih.gov/21502652/ Aging. 2017 Mar 5;9(3):769–77.
277. Strain WD, Lukashevich V, Kothny W, Hoellinger MJ, Paldánius between Asians and non-Asians: a systematic review and meta-analysis.
PM. Individualised treatment targets for elderly patients with type 2 dia- Diabetologia [Internet]. 2013 Apr [cited 2022 Aug 12];56(4):696–708.
betes using vildagliptin add-on or lone therapy (INTERVAL): a 24 week, Available from: https://pubmed.ncbi.nlm.nih.gov/23344728/
randomised, double-blind, placebo-controlled study. The Lancet. 2013 295. Singh A. Incretin response in Asian type 2 diabetes: Are Indians
Aug;382(9890):409–16. different? Indian J Endocrinol Metab. 2015;19(1):30.
278. Dardano A, Penno G, del Prato S, Miccoli R. Optimal therapy of 296. Agarwal P, Jindal C, Sapakal V. Efficacy and Safety of Teneligliptin
type 2 diabetes: a controversial challenge. Aging. 2014 Mar 26;6(3):187– in Indian Patients with Inadequately Controlled Type 2 Diabetes Mellitus:
206. A Randomized, Double-blind Study. Indian J Endocrinol Metab.
279. Josse RG, Chiasson JL, Ryan EA, Lau DCW, Ross SA, Yale JF, 22(1):41–6.
et al. Acarbose in the treatment of elderly patients with type 2 diabetes. 297. Hassanein M, Abdallah K, Schweizer A. A double-blind, random-
Diabetes Res Clin Pract. 2003 Jan;59(1):37–42. ized trial, including frequent patient-physician contacts and Ramadan-
280. Kalra S, Aamir A, Raza A, Das A, Azad Khan A, Shrestha D, et al. focused advice, assessing vildagliptin and gliclazide in patients with type
Place of sulfonylureas in the management of type 2 diabetes mellitus in 2 diabetes fasting during Ramadan: the STEADFAST study. Vasc Health
South Asia: A consensus statement. Indian J Endocrinol Metab. Risk Manag. 2014;10:319–26.
2015;19(5):577. 298. Martin S, Kolb H, Beuth J, van Leendert R, Schneider B, Scherbaum
281. Dunning T, Sinclair A, Colagiuri S. New IDF Guideline for manag- WA. Change in patients’ body weight after 12 months of treatment with
ing type 2 diabetes in older people. Diabetes Res Clin Pract. 2014 glimepiride or glibenclamide in Type 2 diabetes: a multicentre retrospec-
Mar;103(3):538–40. tive cohort study. Diabetologia. 2003 Dec;46(12):1611–7.
282. Karnieli E, Baeres FMM, Dzida G, Ji Q, Ligthelm R, Ross S, et al. 299. Zoungas S, Chalmers J, Neal B, Billot L, Li Q, Hirakawa Y, et al.
Observational Study of Once-Daily Insulin Detemir in People with Type Follow-up of blood-pressure lowering and glucose control in type 2 dia-
2 Diabetes Aged 75 Years or Older. Drugs Aging. 2013 Mar betes. N Engl J Med. 2014 Oct 9;371(15):1392–406.
1;30(3):167–75. 300. George AM, Jacob AG, Fogelfeld L. Lean diabetes mellitus: An
283. Pandya N, DiGenio A, Gao L, Patel M. Efficacy and Safety of emerging entity in the era of obesity. World J Diabetes. 2015;6(4):613.
Insulin Glargine Compared to Other Interventions in Younger and 301. Abubaker M. Teneligliptin in Management of Diabetic Kidney
Older Adults: A Pooled Analysis of Nine Open-Label, Randomized Disease: A Review of Place in Therapy. JOURNAL OF CLINICAL
Controlled Trials in Patients with Type 2 Diabetes. Drugs Aging. 2013 AND DIAGNOSTIC RESEARCH. 2017;
Jun 29;30(6):429–38. 302. Kishimoto M. Teneligliptin: a DPP-4 inhibitor for the treatment of
284. Lee P, Chang A, Blaum C, Vlajnic A, Gao L, Halter J. Comparison type 2 diabetes. Diabetes Metab Syndr Obes. 2013 May;187.
of Safety and Efficacy of Insulin Glargine and Neutral Protamine 303. Penno G, Garofolo M, del Prato S. Dipeptidyl peptidase-4 inhibition
Hagedorn Insulin in Older Adults with Type 2 Diabetes Mellitus: in chronic kidney disease and potential for protection against diabetes-
Results from a Pooled Analysis. J Am Geriatr Soc. 2012 Jan;60(1):51–9. related renal injury. Nutr Metab Cardiovasc Dis. 2016;26(5):361–73.
285. 8. Obesity Management for the Treatment of Type 2 Diabetes: 304. Penno G, Russo, del Prato. Managing diabetic patients with moder-
Standards of Medical Care in Diabetes — 2019. Diabetes Care. 2019 ate or severe renal impairment using DPP-4 inhibitors: focus on
Jan 1;42(Supplement_1):S81–9. vildagliptin. Diabetes Metab Syndr Obes. 2013 Apr;161.
286. Svacina S. Treatment of obese diabetics. Adv Exp Med Biol. 305. Ioannidis I. Diabetes treatment in patients with renal disease: Is the
2012;771:459–64. landscape clear enough? World J Diabetes. 2014;5(5):651.
287. Mearns ES, Sobieraj DM, White CM, Saulsberry WJ, Kohn CG, 306. Use Of Oral Anti-Diabetic Agents In Diabetes With Chronic Kidney
Doleh Y, et al. Comparative Efficacy and Safety of Antidiabetic Drug Disease SV Madhu.
Regimens Added to Metformin Monotherapy in Patients with Type 2 307. Urata H, Mori K, Emoto M, Yamazaki Y, Motoyama K, Morioka T,
Diabetes: A Network Meta-Analysis. PLoS One. 2015 et al. Advantage of insulin glulisine over regular insulin in patients with
Apr 28;10(4):e0125879. type 2 diabetes and severe renal insufficiency. J Ren Nutr. 2015
288. Potts JE, Gray LJ, Brady EM, Khunti K, Davies MJ, Bodicoat DH. Mar;25(2):129–34.
The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Weight 308. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012
Loss in Type 2 Diabetes: A Systematic Review and Mixed Treatment Update. American Journal of Kidney Diseases. 2012 Nov;60(5):850–86.
Comparison Meta-Analysis. PLoS One. 2015;10(6):e0126769. 309. Abe M, Kalantar-Zadeh K. Haemodialysis-induced hypoglycaemia
289. Monami M, Nardini C, Mannucci E. Efficacy and safety of sodium and glycaemic disarrays. Nat Rev Nephrol. 2015 May 7;11(5):302–13.
glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of 310. Moghissi ES. Treating patients with diabetes of long duration: GLP-
randomized clinical trials. Diabetes Obes Metab. 2014 May;16(5):457– 1 receptor agonists and insulin in combination. J Am Osteopath Assoc
66. [Internet]. 2014 [cited 2022 Sep 15];114(5 Suppl 2). Available from:
290. Tosaki T, Kamiya H, Himeno T, Kato Y, Kondo M, Toyota K, et al. https://pubmed.ncbi.nlm.nih.gov/24769505/
Sodium-glucose Co-transporter 2 Inhibitors Reduce the Abdominal 311. Moghissi ES. Treating Patients With Diabetes of Long Duration:
Visceral Fat Area and May Influence the Renal Function in Patients with GLP-1 Receptor Agonists and Insulin in Combination. Journal of
Type 2 Diabetes. Internal Medicine. 2017;56(6):597–604. Osteopathic Medicine. 2014 May 1;114(s52):22–9.
291. Chen JF, Chang CM, Kuo MC, Tung SC, Tsao CF, Tsai CJ. Impact 312. Kalra S. Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A
of baseline body mass index status on glucose lowering and weight Review of Their Basic and Clinical Pharmacology. Diabetes Ther. 2014
change during sitagliptin treatment for type 2 diabetics. Diabetes Res Dec;5(2):355–66.
Clin Pract. 2016 Oct 1;120:8–14. 313. Effect of intensive control of glucose on cardiovascular outcomes
292. Kodera R, Shikata K, Nakamura A, Okazaki S, Nagase R, Nakatou and death in patients with diabetes mellitus: a meta-analysis of
T, et al. The Glucose-lowering Efficacy of Sitagliptin in Obese Japanese randomised controlled trials - Database of Abstracts of Reviews of
Patients with Type 2 Diabetes. Internal Medicine. 2017;56(6):605–13. Effects (DARE): Quality-assessed Reviews - NCBI Bookshelf
293. Mohan V, Yang W, Son HY, Xu L, Noble L, Langdon RB, et al. [Internet]. [cited 2022 Aug 11 ]. Available from: https://
Efficacy and safety of sitagliptin in the treatment of patients with type 2 www.ncbi.nlm.nih.gov/books/NBK77956/
diabetes in China, India, and Korea. Diabetes Res Clin Pract. 2009 314. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S,
Jan;83(1):106–16. et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2
294. Kim YG, Hahn S, Oh TJ, Kwak SH, Park KS, Cho YM. Differences Diabetes. New England Journal of Medicine. 2015
in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors Nov 26;373(22):2117–28.
315. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu 331. Phung OJ. Effect of Noninsulin Antidiabetic Drugs Added to
N, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Metformin Therapy on Glycemic Control, Weight Gain, and
Diabetes. New England Journal of Medicine. 2017 Aug 17;377(7):644– Hypoglycemia in Type 2 Diabetes. JAMA. 2010 Apr 14;303(14):1410.
57. 332. Salvo F, Moore N, Arnaud M, Robinson P, Raschi E, de Ponti F,
316. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann et al. Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and
JFE, Nauck MA, et al. Liraglutide and Cardiovascular Outcomes in risk of hypoglycaemia: systematic review and meta-analysis. BMJ. 2016
Type 2 Diabetes. New England Journal of Medicine. 2016 May 3;i2231.
Jul 28;375(4):311–22. 333. Nauck MA. Update on developments with SGLT2 inhibitors in the
317. Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, management of type 2 diabetes. Drug Des Devel Ther. 2014;8:1335–80.
Pais P, et al. Design and baseline characteristics of participants in the 334. Management of persistent hyperglycemia in type 2 diabetes mellitus
<scp>R</scp> esearching cardiovascular <scp>E</scp> vents with a - UpToDate [Internet]. [cited 2022 Aug 11]. Available from: https://
<scp>W</scp> eekly <scp>IN</scp> cretin in <scp>D</scp> iabetes ( www.uptodate.com/contents/management-of-persistent-hyperglycemia-
<scp>REWIND</scp> ) trial on the cardiovascular effects of dulaglutide. in-type-2-diabetes-mellitus
Diabetes Obes Metab. 2018 Jan 14;20(1):42–9. 335. 4. Comprehensive Medical Evaluation and Assessment of
318. Hernandez AF, Green JB, Janmohamed S, D’Agostino RB, Granger Comorbidities: Standards of Medical Care in Diabetes—2019. Diabetes
CB, Jones NP, et al. Albiglutide and cardiovascular outcomes in patients Care. 2019 Jan 1;42(Supplement_1):S34–45.
with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a 336. Turner R. Effect of intensive blood-glucose control with metformin
double-blind, randomised placebo-controlled trial. Lancet. on complications in overweight patients with type 2 diabetes (UKPDS
2018;392(10157):1519–29. 34). The Lancet [Internet]. 1998 Sep 12 [cited 2022
319. Mahaffey KW, Jardine MJ, Bompoint S, Cannon CP, Neal B, Aug 10];352(9131):854–65. Available from: http://www.thelancet.com/
Heerspink HJL, et al. Canagliflozin and Cardiovascular and Renal article/S0140673698070378/fulltext
Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in 337. Turner R. Intensive blood-glucose control with sulphonylureas or
Primary and Secondary Cardiovascular Prevention Groups. Circulation. insulin compared with conventional treatment and risk of complications
2019;140(9):739–50. in patients with type 2 diabetes (UKPDS 33). The Lancet [Internet]. 1998
320. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter Sep 12 [cited 2022 Aug 10];352(9131):837–53. Available from: http://
LA, et al. Semaglutide and Cardiovascular Outcomes in Patients with www.thelancet.com/article/S0140673698070196/fulltext
Type 2 Diabetes. New England Journal of Medicine. 2016 338. Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular
Nov 10;375(19):1834–44. complications in diabetes mellitus: Distinct or continuum? Indian J
321. Norhammar A, Bodegård J, Nyström T, Thuresson M, Nathanson D, Endocrinol Metab [Internet]. 2016 Jul 1 [cited 2022
Eriksson JW. Dapagliflozin and cardiovascular mortality and disease out- Aug 10];20(4):546–53. Available from: https://
comes in a population with type 2 diabetes similar to that of the pubmed.ncbi.nlm.nih.gov/27366724/
DECLARE-TIMI 58 trial: A nationwide observational study. Diabetes 339. DM N, S G, J L, P C, O C, M D, et al. The effect of intensive
Obes Metab. 2019;21(5):1136–45. treatment of diabetes on the development and progression of long-term
322. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi- complications in insulin-dependent diabetes mellitus. N Engl J Med
Benedetti M, Moules IK, et al. Secondary prevention of macrovascular [Internet]. 1993 Sep 30 [cited 2022 Aug 10];329(14):977–86. Available
events in patients with type 2 diabetes in the PROactive Study from: https://pubmed.ncbi.nlm.nih.gov/8366922/
(PROspective pioglitAzone Clinical Trial In macroVascular Events): a 340. Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S,
randomised controlled trial. The Lancet. 2005 Oct;366(9493):1279–89. et al. Intensive insulin therapy prevents the progression of diabetic mi-
323. Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, crovascular complications in Japanese patients with non-insulin-
Gorman M, et al. Pioglitazone after Ischemic Stroke or Transient dependent diabetes mellitus: a randomized prospective 6-year study.
Ischemic Attack. N Engl J Med. 2016 Apr 7;374(14):1321–31. Diabetes Res Clin Pract [Internet]. 1995 [cited 2022
324. Xu J, Rajaratnam R. Cardiovascular safety of non-insulin pharma- Aug 10];28(2):103–17. Available from: https://
cotherapy for type 2 diabetes. Cardiovasc Diabetol. 2017 Dec 2;16(1):18. pubmed.ncbi.nlm.nih.gov/7587918/
325. Giles TD, Miller AB, Elkayam U, Bhattacharya M, Perez A. 341. Jindal Radhika, Siddiqui Mohammad A, Gupta Nitin. Post-prandial
Pioglitazone and heart failure: results from a controlled study in patients hyperglycaemia. Journal, Indian Academy of Clinical Medicine.
with type 2 diabetes mellitus and systolic dysfunction. J Card Fail. 2008 2013;14.
Aug;14(6):445–52. 342. Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR,
326. Marx N, Rosenstock J, Kahn SE, Zinman B, Kastelein JJ, Lachin Sherwin R, et al. Management of hyperglycemia in type 2 diabetes: A
JM, et al. Design and baseline characteristics of the CARdiovascular consensus algorithm for the initiation and adjustment of therapy: a con-
Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes sensus statement from the American Diabetes Association and the
(CAROLINA®). Diab Vasc Dis Res. 2015 May;12(3):164–74. European Association for the Study of Diabetes. Diabetes Care
327. Patel A, ADVANCE Collaborative Group, MacMahon S, Chalmers [Internet]. 2006 [cited 2022 Aug 10];29(8):1963–72. Available from:
J, Neal B, Woodward M, et al. Effects of a fixed combination of https://pubmed.ncbi.nlm.nih.gov/16873813/
perindopril and indapamide on macrovascular and microvascular out- 343. Ceriello A. The glucose triad and its role in comprehensive
comes in patients with type 2 diabetes mellitus (the ADVANCE trial): a glycaemic control: current status, future management. Int J Clin Pract.
randomised controlled trial. Lancet. 2007 Sep 8;370(9590):829–40. 2010 Nov 23;64(12):1705–11.
328. Bolen S, Tseng Eva, Hutfless Susan, Segal Jodi B, Suarez-Cuervo 344. Ketema EB, Kibret KT. Correlation of fasting and postprandial
Catalina, Berger Zackary, et al. Diabetes Medications for Adults With plasma glucose with HbA1c in assessing glycemic control; systematic
Type 2 Diabetes: An Update [Internet]. 2016. review and meta-analysis. Archives of Public Health. 2015
329. Gallwitz B. The Future of Combination Therapies of Insulin with a Dec 25;73(1):43.
Glucagon-like Peptide-1 Receptor Agonists in Type 2 Diabetes – Is it 345. Aravind S, Saboo B, Sadikot S, Shah SN, Makkar B, Kalra S, et al.
Advantageous? Eur Endocrinol. 2014;10(2):98. Consensus Statement on Management of Post-Prandial Hyperglycemia in
330. Thomsen RW, Baggesen LM, Søgaard M, Pedersen L, Nørrelund H, Clinical Practice in India. J Assoc Physicians India. 2015;63(8):45–58.
Buhl ES, et al. Early glycaemic control in metformin users receiving their 346. Talib SH, Sr B, Korpe JS. An Observational Study on Correlation of
first add-on therapy: a population-based study of 4,734 people with type 2 Fasting and Postprandial Glycemic Status to various HbA1C Quintiles in
diabetes. Diabetologia. 2015 Oct 16;58(10):2247–53. Type II Diabetics [Internet]. Vol. 6, IOSR Journal of Dental and Medical
Sciences (IOSR-JDMS) e-ISSN. Available from: 362. Marathe PH, Gao HX, Close KL. American Diabetes Association
www.iosrjournals.orgwww.iosrjournals.org Standards of Medical Care in Diabetes 2017. J Diabetes [Internet]. 2017
347. Wang JS, Tu ST, Lee IT, Lin SD, Lin SY, Su SL, et al. Contribution Apr 1 [cited 2022 Aug 10];9(4):320–4. Available from: https://
of postprandial glucose to excess hyperglycaemia in Asian type 2 diabetic pubmed.ncbi.nlm.nih.gov/28070960/
patients using continuous glucose monitoring. Diabetes Metab Res Rev. 363. Omori K, Nomoto H, Nakamura A, Takase T, Cho KY, Ono K, et al.
2011 Jan;27(1):79–84. Reduction in glucose fluctuations in elderly patients with type 2 diabetes
348. Monnier L, Lapinski H, Colette C. Contributions of fasting and using repaglinide: A randomized controlled trial of repaglinide vs sulfo-
postprandial plasma glucose increments to the overall diurnal hypergly- nylurea. J Diabetes Investig [Internet]. 2019 Mar 1 [cited 2022
cemia of type 2 diabetic patients: variations with increasing levels of Aug 22];10(2):367–74. Available from: https://
HbA(1c). Diabetes Care [Internet]. 2003 Mar 1 [cited 2022 pubmed.ncbi.nlm.nih.gov/29963781/
Aug 10];26(3):881–5. Available from: https://pubmed.ncbi.nlm.nih.gov/ 364. Singh S. Post-prandial hyperglycemia. Indian J Endocrinol Metab.
12610053/ 2012;16(8):245.
349. Association AD. 2. Classification and Diagnosis of Diabetes: 365. Ogama N, Sakurai T, Kawashima S, Tanikawa T, Tokuda H, Satake
Standards of Medical Care in Diabetes—2019. Diabetes Care [Internet]. S, et al. Postprandial Hyperglycemia Is Associated With White Matter
2019 Jan 1 [cited 2022 Aug 10];42(Supplement_1):S13–28. Available Hyperintensity and Brain Atrophy in Older Patients With Type 2
from: https://diabetesjournals.org/care/article/42/Supplement_1/S13/ Diabetes Mellitus. Front Aging Neurosci [Internet]. 2018 Sep 12 [cited
31150/2-Classification-and-Diagnosis-of-Diabetes 2022 Aug 12];10(SEP). Available from: /pmc/articles/PMC6143668/
350. Dickinson S, Colagiuri S, Faramus E, Petocz P, Brand-Miller JC. 366. Ceriello A. Postprandial Hyperglycemia and Cardiovascular
Postprandial hyperglycemia and insulin sensitivity differ among lean Disease: Is the HEART2D study the answer? Diabetes Care [Internet].
young adults of different ethnicities. J Nutr [Internet]. 2002 [cited 2022 2009 Mar [cited 2022 Aug 10];32(3):521. Available from: /pmc/articles/
Aug 10];132(9):2574–9. Available from: https:// PMC2646040/
pubmed.ncbi.nlm.nih.gov/12221211/ 367. RR H, SM H, JJ M, MA B, B H, TA H, et al. Effect of nateglinide on
351. Tan W, Tan SY, Henry C. Ethnic Variability in Glycemic Response the incidence of diabetes and cardiovascular events. N Engl J Med
to Sucrose and Isomaltulose. Nutrients. 2017 Apr 1;9(4):347. [Internet]. 2010 Apr 22 [cited 2022 Aug 10];362(16):1463–76.
352. Sudhir R, Mohan V. Postprandial Hyperglycemia in Patients with Available from: https://pubmed.ncbi.nlm.nih.gov/20228402/
Type 2 Diabetes Mellitus. Treat Endocrinol. 2002;1(2):105–16. 368. Raz I, Wilson PWF, Strojek K, Kowalska I, Bozikov V, Gitt AK,
353. Abdul-Ghani MA, Williams K, DeFronzo RA, Stern M. What Is the et al. Effects of Prandial Versus Fasting Glycemia on Cardiovascular
Best Predictor of Future Type 2 Diabetes? Diabetes Care. 2007 Outcomes in Type 2 Diabetes: The HEART2D trial. Diabetes Care.
Jun 1;30(6):1544–8. 2009 Mar 1;32(3):381–6.
354. Oh TJ, Lim S, Kim KM, Moon JH, Choi SH, Cho YM, et al. One- 369. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso
hour postload plasma glucose concentration in people with normal glu- M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-
cose homeostasis predicts future diabetes mellitus: a 12-year community- NIDDM randomised trial. The Lancet. 2002 Jun;359(9323):2072–7.
based cohort study. Clin Endocrinol (Oxf) [Internet]. 2017 Apr 1 [cited 370. Holman RR, Coleman RL, Chan JCN, Chiasson JL, Feng H, Ge J,
2022 Aug 10];86(4):513–9. Available from: https:// et al. Effects of acarbose on cardiovascular and diabetes outcomes in
pubmed.ncbi.nlm.nih.gov/27859511/ patients with coronary heart disease and impaired glucose tolerance
355. Jagannathan R, Sevick MA, Li H, Fink D, Dankner R, Chetrit A, (ACE): a randomised, double-blind, placebo-controlled trial. Lancet
et al. Elevated 1-hour plasma glucose levels are associated with Diabetes Endocrinol. 2017 Nov;5(11):877–86.
dysglycemia, impaired beta-cell function, and insulin sensitivity: a pilot 371. Nakagami T. Hyperglycaemia and mortality from all causes and
study from a real world health care setting. Endocrine [Internet]. 2016 from cardiovascular disease in five populations of Asian origin.
Apr 1 [cited 2022 Aug 10];52(1):172–5. Available from: https:// Diabetologia. 2004 Mar 1;47(3):385–94.
pubmed.ncbi.nlm.nih.gov/26419850/ 372. Sacks DB. A1C Versus Glucose Testing: A Comparison. Diabetes
356. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Care. 2011 Feb 1;34(2):518–23.
Wolfson SK. Carotid-Artery Intima and Media Thickness as a Risk 373. Sheu WHH, Rosman A, Mithal A, Chung N, Lim YT,
Factor for Myocardial Infarction and Stroke in Older Adults. New Deerochanawong C, et al. Addressing the burden of type 2 diabetes and
England Journal of Medicine. 1999 Jan 7;340(1):14–22. cardiovascular disease through the management of postprandial
357. Sciacqua A, Miceli S, Carullo G, Greco L, Succurro E, Arturi F, hyperglycaemia: An Asian-Pacific perspective and expert recommenda-
et al. One-Hour Postload Plasma Glucose Levels and Left Ventricular tions. Diabetes Res Clin Pract. 2011 Jun;92(3):312–21.
Mass in Hypertensive Patients. Diabetes Care. 2011 Jun 1;34(6):1406– 374. Reynolds AN, Mann JI, Williams S, Venn BJ. Advice to walk after
11. meals is more effective for lowering postprandial glycaemia in type 2
358. Wu X, Chen H, Wang Y, Li H. The relationship between coronary diabetes mellitus than advice that does not specify timing: a randomised
risk factors and elevated 1-h postload plasma glucose levels in patients crossover study. Diabetologia. 2016 Dec 17;59(12):2572–8.
with established coronary heart disease. Clin Endocrinol (Oxf). 2013 375. Joshi SR. Post-prandial carbohydrate modulation via gut–Indian
Jan;78(1):67–72. perspective. J Assoc Physicians India. 2010 Nov;58:665.
359. Fiorentino TV, Sesti F, Andreozzi F, Pedace E, Sciacqua A, Hribal 376. Mohan V, Radhika G, Sathya RM, Tamil SR, Ganesan A, Sudha V.
ML, et al. One-hour post-load hyperglycemia combined with HbA1c Dietary carbohydrates, glycaemic load, food groups and newly detected
identifies pre-diabetic individuals with a higher cardio-metabolic risk type 2 diabetes among urban Asian Indian population in Chennai, India
burden. Atherosclerosis. 2016 Oct 1;253:61–9. (Chennai Urban Rural Epidemiology Study 59). British Journal of
360. Jesrani G, Gupta M, Kaur J, Kaur N, Lehl S, Singh R. One-Hour Nutrition. 2009 Nov 28;102(10):1498–506.
postload plasma glucose in obese indian adults with nonalcoholic fatty 377. Augustin LSA, Kendall CWC, Jenkins DJA, Willett WC, Astrup A,
liver disease: An observational study from North India. Indian J Barclay AW, et al. Glycemic index, glycemic load and glycemic re-
Endocrinol Metab [Internet]. 2021 [cited 2022 Aug 12];25(5):450. sponse: An International Scientific Consensus Summit from the
Available from: https://journals.lww.com/indjem/Fulltext/2021/09000/ International Carbohydrate Quality Consortium (ICQC). Nutr Metab
One_Hour_Postload_Plasma_Glucose_in_Obese_Indian.14.aspx Cardiovasc Dis. 2015 Sep;25(9):795–815.
361. Mohan V, Vijayaprabha R, Rema M. Vascular complications in 378. Ghosh JM. TRIAL OF LOW GLYCEMIC DIET AND
long-term South Indian NIDDM of over 25 years’ duration. Diabetes ACARBOSE THERAPY FOR CONTROL OF POST-PRANDIAL
Res Clin Pract. 1996 Mar;31(1–3):133–40. HYPERGLYCEMIA IN TYPE 2 DIABETES MELLITUS:
PRELIMINARY REPORT. Vol. 25, INT. J. DIAB. DEV. COUNTRIES. 393. Pasquel FJ, Umpierrez GE. Hyperosmolar hyperglycemic state: a
2005. historic review of the clinical presentation, diagnosis, and treatment.
379. Xiong Q, Li Z, Nie R, Meng X, Yang XJ. Comparison of the Effects Diabetes Care [Internet]. 2014 Nov 1 [cited 2022 Aug 8];37(11):3124–
of a Bean-Based and a White Rice-Based Breakfast Diet on Postprandial 31. Available from: https://pubmed.ncbi.nlm.nih.gov/25342831/
Glucose and Insulin Levels in Chinese Patients with Type 2 Diabetes. 394. Kitabchi AE, Nyenwe EA. Hyperglycemic crises in diabetes
Med Sci Monit [Internet]. 2021 [cited 2022 Aug 12];27:e930349-1. mellitus: diabetic ketoacidosis and hyperglycemic hyperosmolar state.
Available from: /pmc/articles/PMC8020724/ Endocrinol Metab Clin North Am [Internet]. 2006 Dec [cited 2022
380. Yari Z, Behrouz V, Zand H, Pourvali K. New Insight into Diabetes Aug 8];35(4):725–51. Available from: https://pubmed.ncbi.nlm.nih.gov/
Management: From Glycemic Index to Dietary Insulin Index. Curr 17127143/
Diabetes Rev [Internet]. 2020 Sep 26 [cited 2022 Aug 12];16(4):293– 395. Indulekha K, Surendar J, Anjana RM, Geetha L, Gokulakrishnan K,
300. Available from: https://pubmed.ncbi.nlm.nih.gov/31203801/ Pradeepa R, et al. Metabolic obesity, adipocytokines, and inflammatory
381. Yang HK, Lee SH, Shin J, Choi YH, Ahn YB, Lee BW, et al. markers in Asian Indians–CURES-124. Diabetes Technol Ther [Internet].
Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with 2015 Feb 1 [cited 2022 Aug 8];17(2):134–41. Available from: https://
Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double- pubmed.ncbi.nlm.nih.gov/25478993/
Blind, Placebo-Controlled Study. Diabetes Metab J [Internet]. 2019 Jun 1 396. Heller SR. Glucose Concentrations of Less Than 3.0 mmol/L (54
[cited 2022 Aug 12];43(3):287. Available from: /pmc/articles/ mg/dL) Should Be Reported in Clinical Trials: A Joint Position Statement
PMC6581543/ of the American Diabetes Association and the European Association for
382. DURÁN A, MARTÍN P, RUNKLE I, PÉREZ N, ABAD R, the Study of Diabetes. Diabetes Care [Internet]. 2017 Jan 1 [cited 2022
FERNÁNDEZ M, et al. Benefits of self-monitoring blood glucose in Aug 8];40(1):155–7. Available from: https://pubmed.ncbi.nlm.nih.gov/
the management of new-onset Type 2 diabetes mellitus: The St Carlos 27872155/
Study, a prospective randomized clinic-based interventional study with 397. Shriraam V, Mahadevan S, Anitharani M, Jagadeesh N, Kurup S,
parallel groups. J Diabetes. 2010 Sep;2(3):203–11. Vidya T, et al. Reported hypoglycemia in Type 2 diabetes mellitus pa-
383. Franciosi M, Lucisano G, Pellegrini F, Cantarello A, Consoli A, tients: Prevalence and practices-a hospital-based study. Indian J
Cucco L, et al. ROSES: role of self-monitoring of blood glucose and Endocrinol Metab [Internet]. 2017 Jan 1 [cited 2022 Aug 8];21(1):148.
intensive education in patients with Type 2 diabetes not receiving insu- Available from: /pmc/articles/PMC5240057/
lin. A pilot randomized clinical trial. Diabetic Medicine. 2011 398. Vikas PV, Chandrakumar A, Dilip C, Suriyaprakash TNK, Thomas
Jul;28(7):789–96. L, Surendran R. Incidence and risk factors of hypoglycemia among Type
384. Polonsky WH, Fisher L, Schikman CH, Hinnen DA, Parkin CG, 2 diabetic patients in a South Indian hospital. Diabetes Metab Syndr
Jelsovsky Z, et al. Structured Self-Monitoring of Blood Glucose [Internet]. 2016 Apr 1 [cited 2022 Aug 8];10(2 Suppl 1):S22–5.
Significantly Reduces A1C Levels in Poorly Controlled, Noninsulin- Available from: https://pubmed.ncbi.nlm.nih.gov/26806327/
Treated Type 2 Diabetes. Diabetes Care. 2011 Feb 1;34(2):262–7. 399. Kalra S, Mukherjee J, Venkataraman S, Bantwal G, Shaikh S, Saboo
385. Mangrola D, Cox C, Furman AS, Krishnan S, Karakas SE. Self B, et al. Hypoglycemia: The neglected complication. Indian J Endocrinol
Blood Glucose Monitoring Underestimates Hyperglycemia And Metab [Internet]. 2013 [cited 2022 Aug 8];17(5):819. Available from:
Hypoglycemia As Compared To Continuous Glucose Monitoring In https://pubmed.ncbi.nlm.nih.gov/24083163/
Type 1 And Type 2 Diabetes. Endocrine Practice. 2018 Jan;24(1):47–52. 400. WC C, GW E, RP B, DC G, RH G, JA C, et al. Effects of intensive
386. Kesavadev J, Vigersky R, Shin J, Pillai PBS, Shankar A, Sanal G, blood-pressure control in type 2 diabetes mellitus. N Engl J Med
et al. Assessing the Therapeutic Utility of Professional Continuous [Internet]. 2010 Apr 29 [cited 2022 Aug 8];362(17):1575–85. Available
Glucose Monitoring in Type 2 Diabetes Across Various Therapies: A from: https://pubmed.ncbi.nlm.nih.gov/20228401/
Retrospective Evaluation. Adv Ther. 2017 Aug 30;34(8):1918–27. 401. McCoy RG, Shah ND, van Houten HK, Wermers RA, Ziegenfuss
387. Maia FFR, Araújo LR. Efficacy of continuous glucose monitoring JY, Smith SA. Increased mortality of patients with diabetes reporting
system (CGMS) to detect postprandial hyperglycemia and unrecognized severe hypoglycemia. Diabetes Care [Internet]. 2012 Sep [cited 2022
hypoglycemia in type 1 diabetic patients. Diabetes Res Clin Pract. 2007 Aug 8];35(9):1897–901. Available from: https://
Jan;75(1):30–4. pubmed.ncbi.nlm.nih.gov/22699297/
388. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic 402. Zoungas S, Patel A, Chalmers J, de Galan BE, Li Q, Billot L, et al.
crises in adult patients with diabetes. Diabetes Care [Internet]. 2009 Jul Severe hypoglycemia and risks of vascular events and death. N Engl J
[cited 2022 Aug 8];32(7):1335–43. Available from: https:// Med [Internet]. 2010 Oct 7 [cited 2022 Aug 8];363(15):1410–8.
389. Basu A, Close CF, Jenkins D, Krentz AJ, Nattrass M, Wright AD. 403. Expert Group Recommendations on Detection and Management of
Persisting mortality in diabetic ketoacidosis. Diabet Med [Internet]. 1993 Hypoglycemia in Routine Clinical Practice in Insulin Treated Patients
[cited 2022 Aug 8];10(3):282–4. Available from: https:// with Diabetes - PubMed [Internet]. [cited 2022 Aug 8]. Available from:
pubmed.ncbi.nlm.nih.gov/8485963/ https://pubmed.ncbi.nlm.nih.gov/31313564/
390. Malone ML, Gennis V, Goodwin JS. Characteristics of diabetic 404. Gabriely I, Shamoon H. Hypoglycemia in diabetes: common, often
ketoacidosis in older versus younger adults. J Am Geriatr Soc unrecognized. Cleve Clin J Med [Internet]. 2004 [cited 2022
[Internet]. 1992 [cited 2022 Aug 8];40(11):1100–4. Available from: Aug 8];71(4):335–42. Available from: https://pubmed.ncbi.nlm.nih.gov/
https://pubmed.ncbi.nlm.nih.gov/1401693/ 15117175/
391. Bhowmick SK, Levens KL, Rettig KR. Hyperosmolar hyperglyce- 405. Hirsch IB. Hypoglycemia and the hypoglycemic unawareness syn-
mic crisis: an acute life-threatening event in children and adolescents with drome. Diabetes Technol Ther [Internet]. 2000 [cited 2022 Aug 8];2
type 2 diabetes mellitus. Endocr Pract [Internet]. 2005 [cited 2022 Suppl 1(SUPPL. 1). Available from: https://pubmed.ncbi.nlm.nih.gov/
Aug 8];11(1):23–9. Available from: https://pubmed.ncbi.nlm.nih.gov/ 11469638/
16033732/ 406. Lu B, Ghavaminejad A, Liu JF, Li J, Mirzaie S, Giacca A, et al.
392. Fadini GP, de Kreutzenberg SV, Rigato M, Brocco S, Marchesan M, “smart” Composite Microneedle Patch Stabilizes Glucagon and Prevents
Tiengo A, et al. Characteristics and outcomes of the hyperglycemic Nocturnal Hypoglycemia: Experimental Studies and Molecular
hyperosmolar non-ketotic syndrome in a cohort of 51 consecutive cases Dynamics Simulation. ACS Appl Mater Interfaces [Internet]. 2021 [cited
at a single center. Diabetes Res Clin Pract [Internet]. 2011 Nov [cited 2022 Aug 26]; Available from: https://pubs.acs.org/doi/abs/10.1021/
2022 Aug 8];94(2):172–9. Available from: https:// acsami.1c24955
pubmed.ncbi.nlm.nih.gov/21752485/
407. Gilmore L, Freeman S, Amarasekara S, Maza A, Setji T. Evaluation 421. Viswanathan M, Joshi S, Bhansali A, Badgandi M, Chowdhury S,
of the Efficacy of a Hypoglycemia Protocol to Treat Severe Deshpande N, et al. Hypoglycemia in type 2 diabetes: Standpoint of an
Hypoglycemia. Clinical Nurse Specialist. 2022 Jul;36(4):196–203. experts’ committee (India hypoglycemia study group). Indian J
408. Shafiee G, Mohajeri-Tehrani M, Pajouhi M, Larijani B. The impor- Endocrinol Metab [Internet]. 2012 [cited 2022 Aug 8];16(6):894.
tance of hypoglycemia in diabetic patients. J Diabetes Metab Disord Available from: /pmc/articles/PMC3510957/
[Internet]. 2012 Oct 1 [cited 2022 Aug 8];11(1):17. Available from: 422. Gadkari SS, Maskati QB, Nayak BK. Prevalence of diabetic retinop-
/pmc/articles/PMC3598174/ athy in India: The All India Ophthalmological Society Diabetic
409. Ahmedani MY, Haque MS, Basit A, Fawwad A, Alvi SFD. Retinopathy Eye Screening Study 2014. Indian J Ophthalmol [Internet].
Ramadan Prospective Diabetes Study: the role of drug dosage and timing 2016 Jan 1 [cited 2022 Aug 10];64(1):38–44. Available from: https://
alteration, active glucose monitoring and patient education. Diabet Med pubmed.ncbi.nlm.nih.gov/26953022/
[Internet]. 2012 Jun [cited 2022 Aug 8];29(6):709–15. Available from: 423. Patil S, Gogate P, Vora S, Ainapure S, Hingane R, Kulkarni A, et al.
https://pubmed.ncbi.nlm.nih.gov/22587405/ Prevalence, causes of blindness, visual impairment and cataract surgical
410. Bravis V, Hui E, Salih S, Mehar S, Hassanein M, Devendra D. services in Sindhudurg district on the western coastal strip of India. Indian
Ramadan Education and Awareness in Diabetes (READ) programme J Ophthalmol [Internet]. 2014 Feb [cited 2022 Aug 10];62(2):240–5.
for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Available from: https://pubmed.ncbi.nlm.nih.gov/24618491/
Med [Internet]. 2010 [cited 2022 Aug 8];27(3):327–31. Available from: 424. Parameswarappa D, Rajalakshmi R, Mohamed A, Kavya S,
https://pubmed.ncbi.nlm.nih.gov/20536496/ Munirathnam H, Manayath G, et al. Severity of diabetic retinopathy
411. Norris SL, Lau J, Smith SJ, Schmid CH, Engelgau MM. Self- and its relationship with age at onset of diabetes mellitus in India: A
management education for adults with type 2 diabetes: a meta-analysis multicentric study. Indian J Ophthalmol. 2021;69(11):3255.
of the effect on glycemic control. Diabetes Care [Internet]. 2002 Jul [cited 425. Association AD. 11. Microvascular Complications and Foot Care:
2022 Aug 8];25(7):1159–71. Available from: https:// Standards of Medical Care in Diabetes—2019. Diabetes Care [Internet].
pubmed.ncbi.nlm.nih.gov/12087014/ 2019 Jan 1 [cited 2022 Aug 12];42(Supplement_1):S124–38. Available
412. Managing hypoglycemia in primary care - PubMed [Internet]. [cited from: https://diabetesjournals.org/care/article/42/Supplement_1/S124/
2022 Aug 8]. Available from: https://pubmed.ncbi.nlm.nih.gov/ 30896/11-Microvascular-Complications-and-Foot-Care
23106068/ 426. Yau JWY, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW,
413. Noh RM, Graveling AJ, Frier BM. Medically minimising the impact Bek T, et al. Global prevalence and major risk factors of diabetic retinop-
of hypoglycaemia in type 2 diabetes: a review. Expert Opin Pharmacother athy. Diabetes Care [Internet]. 2012 Mar [cited 2022 Aug 12];35(3):556–
[Internet]. 2011 Oct [cited 2022 Aug 8];12(14):2161–75. Available from: 64. Available from: https://pubmed.ncbi.nlm.nih.gov/22301125/
https://pubmed.ncbi.nlm.nih.gov/21668402/ 427. Xu XH, Sun B, Zhong S, Wei DD, Hong Z, Dong AQ. Diabetic
414. Heller SR, Choudhary P, Davies C, Emery C, Campbell MJ, retinopathy predicts cardiovascular mortality in diabetes: a meta-analysis.
Freeman J, et al. Risk of hypoglycaemia in types 1 and 2 diabetes: effects BMC Cardiovasc Disord [Internet]. 2020 Dec 1 [cited 2022
of treatment modalities and their duration. Diabetologia [Internet]. 2007 Aug 13];20(1):1–8. Available from: https://
Jun [cited 2022 Aug 8];50(6):1140–7. Available from: https:// bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-020-
pubmed.ncbi.nlm.nih.gov/17415551/ 01763-z
415. Diabetes SBCI in the M of T 2, 2009 undefined. Safety and effec- 428. Sosale A, Prasanna Kumar K, Sadikot S, Nigam A, Bajaj S, Zargar
tiveness of modern insulin therapy. academia.edu [Internet]. [cited 2022 A, et al. Chronic complications in newly diagnosed patients with Type 2
Aug 8]; Available from: https://www.academia.edu/download/ diabetes mellitus in India. Indian J Endocrinol Metab [Internet]. 2014
42624169/0907Con_DiabetesSup_HR.pdf#page=11 May 1 [cited 2022 Aug 10];18(3):355–60. Available from: https://
416. Garber AJ, Clauson P, Pedersen CB, Kølendorf K. Lower risk of pubmed.ncbi.nlm.nih.gov/24944931/
hypoglycemia with insulin detemir than with neutral protamine hagedorn 429. Sosale B, Sosale A, Mohan A, Kumar P, Saboo B, Kandula S.
insulin in older persons with type 2 diabetes: a pooled analysis of phase Cardiovascular risk factors, micro and macrovascular complications at
III trials. J Am Geriatr Soc [Internet]. 2007 Nov [cited 2022 diagnosis in patients with young onset type 2 diabetes in India: CINDI
Aug 8];55(11):1735–40. Available from: https:// 2. Indian J Endocrinol Metab [Internet]. 2016 Jan 1 [cited 2022
pubmed.ncbi.nlm.nih.gov/17979896/ Aug 10];20(1):114–8. Available from: https://pubmed.ncbi.nlm.nih.gov/
417. Indirect comparison of once daily insulin detemir and glargine in 26904479/
reducing weight gain and hypoglycaemic episodes when administered in 430. Rani PK, Raman R, Agarwal S, Paul PG, Uthra S, Margabandhu G,
addition to conventional oral anti-diabetic therapy in patients with type-2 et al. Diabetic retinopathy screening model for rural population: aware-
diabetes - Database of Abstracts of Reviews of Effects (DARE): Quality- ness and screening methodology. Rural Remote Health. 5(4):350.
assessed Reviews - NCBI Bookshelf [Internet]. [cited 2022 Aug 8]. 431. Chakrabarti R, Chatterjee T. Tip of the Iceberg: The Need for
Available from: https://www.ncbi.nlm.nih.gov/books/NBK76225/ Diabetic Retinopathy Screening in Developing Countries. Lessons
418. Chan SP, Colagiuri S. Systematic review and meta-analysis of the From Vietnam. Asia Pac J Ophthalmol (Phila) [Internet]. 2013 [cited
efficacy and hypoglycemic safety of gliclazide versus other insulinotropic 2022 Aug 10];2(2):76–8. Available from: https://
agents. Diabetes Res Clin Pract [Internet]. 2015 Oct 1 [cited 2022 pubmed.ncbi.nlm.nih.gov/26108042/
Aug 8];110(1):75–81. Available from: https://pubmed.ncbi.nlm.nih.gov/ 432. Unnikrishnan AG, Kalra S, Tandon N. Diabetic retinopathy care in
26361859/ India: An endocrinology perspective. Indian J Endocrinol Metab
419. Draeger KE, Wernicke-Panten K, Lomp HJ, Schüler E, Roßkamp R. [Internet]. 2016 Apr 1 [cited 2022 Aug 10];20(Suppl 1):S1–2.
Long-term treatment of type 2 diabetic patients with the new oral antidi- Available from: https://pubmed.ncbi.nlm.nih.gov/27144130/
abetic agent glimepiride (Amaryl): a double-blind comparison with 433. Ulbig MW, Kollias AN. Diabetic retinopathy: Early diagnosis and
glibenclamide. Horm Metab Res [Internet]. 1996 [cited 2022 effective treatment. Dtsch Arztebl Int [Internet]. 2010 Feb 5 [cited 2022
Aug 8];28(9):419–25. Available from: https://pubmed.ncbi.nlm.nih.gov/ Aug 10];107(5):75–84. Available from: https://
8911976/ pubmed.ncbi.nlm.nih.gov/20186318/
420. Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin 434. Hammes HP. Optimal treatment of diabetic retinopathy. Ther Adv
antidiabetic drugs added to metformin therapy on glycemic control, Endocrinol Metab [Internet]. 2013 [cited 2022 Aug 10];4(2):61–71.
weight gain, and hypoglycemia in type 2 diabetes. JAMA [Internet]. Available from: https://pubmed.ncbi.nlm.nih.gov/23626903/
2010 Apr 14 [cited 2022 Aug 8];303(14):1410–8. Available from: 435. Standards of medical care in diabetes-2015 abridged for primary
https://pubmed.ncbi.nlm.nih.gov/20388897/ care providers. Clin Diabetes [Internet]. 2015 [cited 2022
Aug 10];33(2):97–111. Available from: https:// Chennai Urban Rural Epidemiology Study (CURES) Eye Study 4. Diabet
pubmed.ncbi.nlm.nih.gov/25897193/ Med [Internet]. 2008 May [cited 2022 Aug 10];25(5):536–42. Available
436. Garg S, Davis RM. Diabetic Retinopathy Screening Update. Clinical from: https://pubmed.ncbi.nlm.nih.gov/18346159/
Diabetes. 2009 Jan 1;27(4):140–5. 450. Shah A, Kanaya AM. Diabetes and associated complications in the
437. Morrison JL, Hodgson LAB, Lim LL, Al-Qureshi S. Diabetic reti- South Asian population. Curr Cardiol Rep [Internet]. 2014 [cited 2022
nopathy in pregnancy: a review. Clin Exp Ophthalmol [Internet]. 2016 Aug 10];16(5). Available from: https://pubmed.ncbi.nlm.nih.gov/
May 1 [cited 2022 Aug 10];44(4):321–34. Available from: https:// 24643902/
pubmed.ncbi.nlm.nih.gov/27062093/ 451. Pradeepa R, Anjana RM, Unnikrishnan R, Ganesan A, Mohan V,
438. Sen S, Ramasamy K, Vignesh TP, Kannan NB, Sivaprasad S, Rema M. Risk factors for microvascular complications of diabetes among
Rajalakshmi R, et al. Identification of risk factors for targeted diabetic South Indian subjects with type 2 diabetes–the Chennai Urban Rural
retinopathy screening to urgently decrease the rate of blindness in people Epidemiology Study (CURES) Eye Study-5. Diabetes Technol Ther
with diabetes in India. Indian J Ophthalmol [Internet]. 2021 Nov 1 [cited [Internet]. 2010 Oct 1 [cited 2022 Aug 10];12(10):755–61. Available
2022 Aug 13];69(11):3156–64. Available from: https:// from: https://pubmed.ncbi.nlm.nih.gov/20818974/
journals.lww.com/ijo/Fulltext/2021/11000/ 452. Gopinath M, N PR, Hafeez M, An R. To Study the Incidence of
Identification_of_risk_factors_for_targeted.42.aspx Diabetic Retinopathy in Different Stages of Diabetic Nephropathy in
439. Scarpa G, Urban F, Vujosevic S, Tessarin M, Gallo G, Visentin A, Type 2 Diabetes Mellitus. J Assoc Physicians India. 2022
et al. The Nonmydriatic Fundus Camera in Diabetic Retinopathy Apr;70(4):11–2.
Screening: A Cost-Effective Study with Evaluation for Future Large- 453. Chawla S, Trehan S, Chawla A, Jaggi S, Chawla R, Kumar V, et al.
Scale Application. J Ophthalmol [Internet]. 2016 [cited 2022 Relationship between diabetic retinopathy microalbuminuria and other
Aug 10];2016. Available from: https://pubmed.ncbi.nlm.nih.gov/ modifiable risk factors. Prim Care Diabetes. 2021;15(3):567–70.
27885337/ 454. Ezhilvendhan K, Sathiyamoorthy A, Prakash B, Bhava B, Shenoy
440. Egan AM, McVicker L, Heerey A, Carmody L, Harney F, Dunne A. Association of dyslipidemia with diabetic retinopathy in type 2 diabe-
FP. Diabetic retinopathy in pregnancy: a population-based study of wom- tes mellitus patients: A hospital-based study. J Pharm Bioallied Sci
en with pregestational diabetes. J Diabetes Res [Internet]. 2015 [cited [Internet]. 2021 Nov 1 [cited 2022 Aug 13];13(6):1062. Available from:
2022 Aug 10];2015. Available from: https://pubmed.ncbi.nlm.nih.gov/ https://www.jpbsonline.org/article.asp?issn=0975-
25945354/ 7406;year=2021;volume=13;issue=6;spage=
441. Mallika P, Tan A, S A, T A, Alwi SS, Intan G. Diabetic retinopathy 1062;epage=1067;aulast=Ezhilvendhan
and the effect of pregnancy. Malays Fam Physician. 2010;5(1):2–5. 455. Chawla A, Chawla R, Jaggi S, Singh D. Trained nurse operated
442. Lauszus F, Klebe JG, Bek T. Diabetic retinopathy in pregnancy telemedicine-based retinal examination- A novel cost-effective model
during tight metabolic control. Acta Obstet Gynecol Scand. 2000 for the developing world. Endocrine Practice. 2016;
May;79(5):367–70. 456. Eszes DJ, Szabó DJ, Russell G, Kirby P, Paulik E, Nagymajtényi L,
443. Chen Z, Lin X, Qu B, Gao W, Zuo Y, Peng W, et al. Preoperative et al. Diabetic Retinopathy Screening Using Telemedicine Tools: Pilot
Expectations and Postoperative Outcomes of Visual Functioning among Study in Hungary. J Diabetes Res [Internet]. 2016 [cited 2022
Cataract Patients in Urban Southern China. PLoS One [Internet]. 2017 Aug 10];2016. Available from: https://pubmed.ncbi.nlm.nih.gov/
Jan 1 [cited 2022 Aug 10];12(1). Available from: https:// 28078306/
pubmed.ncbi.nlm.nih.gov/28068402/ 457. Singh R, Kishore L, Kaur N. Diabetic peripheral neuropathy: current
444. Raymond NT, Barnett AH, Varadhan L, Kumar S, Reynold DR, perspective and future directions. Pharmacol Res. 2014 Feb;80:21–35.
O’Hare JP, et al. Higher prevalence of retinopathy in diabetic patients of 458. Bayram EH, Sezer AD, Elçioğlu HK. Diabetic neuropathy and treat-
South Asian ethnicity compared with white Europeans in the community: ment strategy-new challenges and applications. Smart Drug Delivery
a cross-sectional study. Diabetes Care [Internet]. 2009 Mar [cited 2022 System. 2016;373.
Aug 10];32(3):410–5. Available from: https://pubmed.ncbi.nlm.nih.gov/ 459. Darivemula S, Nagoor K, Patan SK, Reddy NB, Deepthi CS,
19074992/ Chittooru CS. Prevalence and Its Associated Determinants of Diabetic
445. Rema M, Premkumar S, Anitha B, Deepa R, Pradeepa R, Mohan V. Peripheral Neuropathy (DPN) in Individuals Having Type-2 Diabetes
Prevalence of diabetic retinopathy in urban India: the Chennai Urban Mellitus in Rural South India. Indian J Community Med [Internet].
Rural Epidemiology Study (CURES) eye study, I. Invest Ophthalmol 2019 Apr 1 [cited 2022 Aug 13];44(2):88. Available from: /pmc/arti-
Vis Sci [Internet]. 2005 [cited 2022 Aug 10];46(7):2328–33. Available cles/PMC6625262/
from: https://pubmed.ncbi.nlm.nih.gov/15980218/ 460. Snyder MJ, Gibbs LM, Lindsay TJ. Treating Painful Diabetic
446. PR R, MR R, BW G, RG V, MU J. Prevalence of Diabetic Peripheral Neuropathy: An Update. Am Fam Physician. 2016
Retinopathy in Western Indian Type 2 Diabetic Population: A Hospital Aug 1;94(3):227–34.
- based Cross - Sectional Study. J Clin Diagn Res [Internet]. 2013 [cited 461. Gill H, Yadav S, Ramesh V, Bhatia E. A prospective study of
2022 Aug 10];7(7). Available from: https://pubmed.ncbi.nlm.nih.gov/ prevalence and association of peripheral neuropathy in Indian patients
23998071/ with newly diagnosed type 2 diabetes mellitus. J Postgrad Med
447. Raman R, Ganesan S, Pal SS, Kulothungan V, Sharma T. [Internet]. 2014 Jul 1 [cited 2022 Aug 10];60(3):270–5. Available from:
Prevalence and risk factors for diabetic retinopathy in rural India. https://pubmed.ncbi.nlm.nih.gov/25121366/
Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular 462. Rani PK, Raman R, Rachapalli SR, Pal SS, Kulothungan V, Sharma
Genetic Study III (SN-DREAMS III), report no 2. BMJ Open Diabetes T. Prevalence and risk factors for severity of diabetic neuropathy in type 2
Res Care [Internet]. 2014 Jun [cited 2022 Aug 10];2(1):e000005. diabetes mellitus. Indian J Med Sci. 2010 Feb;64(2):51–7.
Available from: https://pubmed.ncbi.nlm.nih.gov/25452856/ 463. Sosale A, Prasanna Kumar K, Sadikot S, Nigam A, Bajaj S, Zargar
448. Jotheeswaran AT, Lovakanth N, Nadiga S, Anchala R, Murthy A, et al. Chronic complications in newly diagnosed patients with Type 2
GVS, Gilbert CE. Estimating the proportion of persons with diabetes diabetes mellitus in India. Indian J Endocrinol Metab [Internet]. 2014
developing diabetic retinopathy in India: A systematic review and meta- May 1 [cited 2022 Aug 10];18(3):355–60. Available from: https://
analysis. Indian J Endocrinol Metab [Internet]. 2016 Apr 1 [cited 2022 pubmed.ncbi.nlm.nih.gov/24944931/
Aug 10];20(Suppl 1):S51–8. Available from: https:// 464. Sosale B, Sosale A, Mohan A, Kumar P, Saboo B, Kandula S.
pubmed.ncbi.nlm.nih.gov/27144137/ Cardiovascular risk factors, micro and macrovascular complications at
449. Pradeepa R, Anitha B, Mohan V, Ganesan A, Rema M. Risk factors diagnosis in patients with young onset type 2 diabetes in India: CINDI
for diabetic retinopathy in a South Indian Type 2 diabetic population–the 2. Indian J Endocrinol Metab [Internet]. 2016 Jan 1 [cited 2022
Aug 10];20(1):114–8. Available from: https://pubmed.ncbi.nlm.nih.gov/ an Independent Risk Factor for Coronary Arterial Disease in Type 2
26904479/ Diabetic Patients - A Retrospective Single Centre Real-World Evidence
465. Juster-Switlyk K, Smith AG. Updates in diabetic peripheral neurop- Study in Indian Population. Exclusive Real World Evidence Journal.
athy. F1000Res [Internet]. 2016 [cited 2022 Aug 10];5. Available from: 2021 Jul 1;1(1).
https://pubmed.ncbi.nlm.nih.gov/27158461/ 482. Chawla R, Bhoopathi A, Punyani H. Ferritin and serum iron as
466. Kakrani AL, Gokhale VS, Vohra K v, Chaudhary N. Clinical and surrogate markers of poor glycemic control and microvascular complica-
nerve conduction study correlation in patients of diabetic neuropathy. J tions in type 2 diabetes mellitus. Int J Diabetes Dev Ctries. 2019
Assoc Physicians India. 2014 Jan;62(1):24–7. Apr 4;39(2):362–8.
467. Bhuyan A, Baro A, Sarma D, Choudhury B. A Study of Cardiac 483. Chawla S, Trehan S, Chawla A, Jaggi S, Chawla R. Clustered met-
Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus: A abolic approach using HbA1c, BP, and aortic augmentation index in type
Northeast India Experience. Indian J Endocrinol Metab [Internet]. 2019 2 diabetes as a tool for risk stratification. Journal of Diabetology
[cite d 2022 Aug 13];23(2):246. Available from: https:// [Internet]. 2021 [cited 2022 Aug 13];12(2):172. Available from: https://
pubmed.ncbi.nlm.nih.gov/31161112/ www.journalofdiabetology.org/article.asp?issn=2078-
468. Agashe S, Petak S. Cardiac Autonomic Neuropathy in Diabetes 7 6 8 5 ; y e a r = 2 0 2 1 ; v o l u m e =
Mellitus. Methodist Debakey Cardiovasc J. 14(4):251–6. 12;issue=2;spage=172;epage=175;aulast=Chawla
469. Srinivasan S, Dehghani C, Pritchard N, Edwards K, Russell AW, 484. Chawla R, Sahu J, Punyani H, Jaggi S. Evaluation of platelet volume
Malik RA, et al. Optical coherence tomography predicts 4-year incident indices as predictive biomarkers of microvascular complications in pa-
diabetic neuropathy. Ophthalmic and Physiological Optics. 2017 tients with type 2 diabetes. Int J Diabetes Dev Ctries. 2021
Jul 1;37(4):451–9. Jan 14;41(1):89–93.
470. Am VD, Siddiqui MS, Khandelwal E. Cardiac Autonomic 485. Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V,
Neuropathy (Can) in Newly Diagnosed Type 2 Diabetes Mellitus Hes M, et al. Gabapentin for the symptomatic treatment of painful neu-
Patients. J Assoc Physicians India. 2022 Apr;70(4):11–2. ropathy in patients with diabetes mellitus: a randomized controlled trial.
471. Bansal D, Gudala K, Muthyala H, Esam HP, Nayakallu R, Bhansali JAMA [Internet]. 1998 Dec 2 [cited 2022 Aug 10];280(21):1831–6.
A. Prevalence and risk factors of development of peripheral diabetic Available from: https://pubmed.ncbi.nlm.nih.gov/9846777/
neuropathy in type 2 diabetes mellitus in a tertiary care setting. J 486. Javed S, Petropoulos IN, Alam U, Malik RA. Treatment of painful
Diabetes Investig [Internet]. 2014 Nov 1 [cited 2022 Aug 10];5(6):714– diabetic neuropathy. Ther Adv Chronic Dis [Internet]. 2015 [cited 2022
21. Available from: https://pubmed.ncbi.nlm.nih.gov/25422773/ Aug 10];6(1):15–28. Available from: https://pubmed.ncbi.nlm.nih.gov/
472. Kannan MA, Sarva S, Kandadai RM, Paturi VR, Jabeen SA, 25553239/
Borgohain R. Prevalence of neuropathy in patients with impaired glucose 487. Arezzo JC, Rosenstock J, LaMoreaux L, Pauer L. Efficacy and
tolerance using various electrophysiological tests. Neurol India [Internet]. safety of pregabalin 600 mg/d for treating painful diabetic peripheral
2014 Nov 1 [cited 2022 Aug 10];62(6):656–61. Available from: https:// neuropathy: a double-blind placebo-controlled trial. BMC Neurol
pubmed.ncbi.nlm.nih.gov/25591680/ [Internet]. 2008 Sep 16 [cited 2022 Aug 10];8. Available from: https://
473. Meijer JWG, Smit AJ, Sonderen E v., Groothoff JW, Eisma WH, pubmed.ncbi.nlm.nih.gov/18796160/
Links TP. Symptom scoring systems to diagnose distal polyneuropathy in 488. Richter RW, Portenoy R, Sharma U, Lamoreaux L, Bockbrader H,
diabetes: the Diabetic Neuropathy Symptom score. Diabet Med Knapp LE. Relief of painful diabetic peripheral neuropathy with
[Internet]. 2002 [cited 2022 Aug 10];19(11):962–5. Available from: pregabalin: a randomized, placebo-controlled trial. J Pain [Internet].
https://pubmed.ncbi.nlm.nih.gov/12421436/ 2005 [cited 2022 Aug 10];6(4):253–60. Available from: https://
474. Boulton AJM. Management of Diabetic Peripheral Neuropathy. pubmed.ncbi.nlm.nih.gov/15820913/
Clinical Diabetes. 2005 Jan 1;23(1):9–15. 489. Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA.
475. Hussain G, Rizvi SAA, Singhal S, Zubair M, Ahmad J. Cross sec- Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev.
tional study to evaluate the effect of duration of type 2 diabetes mellitus 2019;1:CD007076.
on the nerve conduction velocity in diabetic peripheral neuropathy. 490. Roy MK, Kuriakose AS, Varma SK, Jacob LA, Beegum NJ. A study
Diabetes Metab Syndr. 8(1):48–52. on comparative efficacy and cost effectiveness of Pregabalin and
476. Afifi L, Abdelalim A, Ashour A, Al-Athwari A. Correlation between Duloxetine used in diabetic neuropathic pain. Diabetes Metab Syndr
clinical neuropathy scores and nerve conduction studies in patients with [Internet]. 2017 Jan 1 [cited 2022 Aug 10];11(1):31–5. Available from:
diabetic peripheral neuropathy. Egypt J Neurol Psychiatr Neurosurg. https://pubmed.ncbi.nlm.nih.gov/27484440/
2016;53(4):248. 491. Ormseth MJ, Scholz BA, Boomershine CS. Duloxetine in the man-
477. Asad A, Hameed MA, Khan UA, Butt M ur RA, Ahmed N, Nadeem agement of diabetic peripheral neuropathic pain. Patient Prefer
A. Comparison of nerve conduction studies with diabetic neuropathy Adherence [Internet]. 2011 [cited 2022 Aug 10];5:343–56. Available
symptom score and diabetic neuropathy examination score in type-2 di- from: https://pubmed.ncbi.nlm.nih.gov/21845034/
abetics for detection of sensorimotor polyneuropathy. J Pak Med Assoc. 492. Smith T, Nicholson RA. Review of duloxetine in the management of
2009 Sep;59(9):594–8. diabetic peripheral neuropathic pain. Vasc Health Risk Manag.
478. Kamel SR, Hamdy M, Abo Omar HAS, Kamal A, Ali LH, Abd 2007;3(6):833–44.
Elkarim AH. Clinical diagnosis of distal diabetic polyneuropathy using 493. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs.
neurological examination scores: correlation with nerve conduction stud- placebo in patients with painful diabetic neuropathy. Pain [Internet]. 2005
ies. Egyptian Rheumatology and Rehabilitation. 2015 Jul 31;42(3):128– Jul [cited 2022 Aug 10];116(1–2):109–18. Available from: https://
36. pubmed.ncbi.nlm.nih.gov/15927394/
479. Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular 494. Raskin J, Pritchett YL, Wang F, D’Souza DN, Waninger AL,
complications in diabetes mellitus: Distinct or continuum? Indian J Iyengar S, et al. A double-blind, randomized multicenter trial comparing
Endocrinol Metab. 20(4):546–51. duloxetine with placebo in the management of diabetic peripheral neuro-
480. Chawla A, Bhasin G, Chawla R. Validation of neuropathy symp- pathic pain. Pain Med. 6(5):346–56.
toms score (NSS) and neuropathy disability score (NDS) in the clinical 495. Wernicke JF, Pritchett YL, D’Souza DN, Waninger A, Tran P,
diagnosis of peripheral neuropathy in middle aged people with diabetes. Iyengar S, et al. A randomized controlled trial of duloxetine in diabetic
Int J Family Practice. 2013; peripheral neuropathic pain. Neurology [Internet]. 2006 Oct [cited 2022
481. Trehan S, Chawla R, Jaggi S, S A, Palukuri S, Deka S, et al. Aug 10];67(8):1411–20. Available from: https://
Association of Abnormal Brachial Index with Diabetic Nephropathy as pubmed.ncbi.nlm.nih.gov/17060567/
496. Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful 509. Reidy K, Kang HM, Hostetter T, Susztak K. Molecular mechanisms
neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev of diabetic kidney disease. J Clin Invest [Internet]. 2014 Jun 2 [cited 2022
[Internet]. 2014 Jan 3 [cited 2022 Aug 10];2014(1). Available from: Aug 10];124(6):2333–40. Available from: https://
https://pubmed.ncbi.nlm.nih.gov/24385423/ pubmed.ncbi.nlm.nih.gov/24892707/
497. Christoph T, Schröder W, Tallarida RJ, de Vry J, Tzschentke TM. 510. Ahmad J. Management of diabetic nephropathy: Recent progress
Spinal-supraspinal and intrinsic μ-opioid receptor agonist-norepinephrine and future perspective. Diabetes Metab Syndr [Internet]. 2015 Oct 1 [cit-
reuptake inhibitor (MOR-NRI) synergy of tapentadol in diabetic heat ed 2022 Aug 10];9(4):343–58. Available from: https://
hyperalgesia in mice. J Pharmacol Exp Ther [Internet]. 2013 [cited pubmed.ncbi.nlm.nih.gov/25845297/
2022 Aug 10];347(3):794–801. Available from: https:// 511. Agarwal SK, Srivastava RK. Chronic kidney disease in India: chal-
pubmed.ncbi.nlm.nih.gov/24051022/ lenges and solutions. Nephron Clin Pract [Internet]. 2009 Mar [cited 2022
498. Schwartz S, Etropolski M, Shapiro DY, Okamoto A, Lange R, Aug 10];111(3). Available from: https://pubmed.ncbi.nlm.nih.gov/
Haeussler J, et al. Safety and efficacy of tapentadol ER in patients with 19194110/
painful diabetic peripheral neuropathy: results of a randomized-with- 512. Prasannakumar M, Rajput R, Seshadri K, Talwalkar P, Agarwal P,
drawal, placebo-controlled trial. Curr Med Res Opin [Internet]. 2011 Gokulnath G, et al. An observational, cross-sectional study to assess the
Jan [cited 2022 Aug 10];27(1):151–62. Available from: https:// prevalence of chronic kidney disease in type 2 diabetes patients in India
pubmed.ncbi.nlm.nih.gov/21162697/ (START -India). Indian J Endocrinol Metab [Internet]. 2015 Jul 1 [cited
499. Vinik AI, Shapiro DY, Rauschkolb C, Lange B, Karcher K, Pennett 2022 Aug 10];19(4):520–3. Available from: https://
D, et al. A randomized withdrawal, placebo-controlled study evaluating pubmed.ncbi.nlm.nih.gov/26180769/
the efficacy and tolerability of tapentadol extended release in patients 513. Sosale A, Prasanna Kumar K, Sadikot S, Nigam A, Bajaj S, Zargar
with chronic painful diabetic peripheral neuropathy. Diabetes Care A, et al. Chronic complications in newly diagnosed patients with Type 2
[Internet]. 2014 [cited 2022 Aug 10];37(8):2302–9. Available from: diabetes mellitus in India. Indian J Endocrinol Metab [Internet]. 2014
https://pubmed.ncbi.nlm.nih.gov/24848284/ May 1 [cited 2022 Aug 11];18(3):355–60. Available from: https://
500. Duehmke RM, Derry S, Wiffen PJ, Bell RF, Aldington D, Moore pubmed.ncbi.nlm.nih.gov/24944931/
RA. Tramadol for neuropathic pain in adults. Cochrane Database Syst 514. Sosale B, Sosale A, Mohan A, Kumar P, Saboo B, Kandula S.
Rev [Internet]. 2017 Jun 15 [cited 2022 Aug 10];6(6). Available from: Cardiovascular risk factors, micro and macrovascular complications at
https://pubmed.ncbi.nlm.nih.gov/28616956/ diagnosis in patients with young onset type 2 diabetes in India: CINDI
501. Morón Merchante I, Pergolizzi J v., van de Laar M, Mellinghoff HU, 2. Indian J Endocrinol Metab [Internet]. 2016 Jan 1 [cited 2022
Nalamachu S, O’Brien J, et al. Tramadol/Paracetamol fixed-dose combi- Aug 11];20(1):114–8. Available from: https://pubmed.ncbi.nlm.nih.gov/
nation for chronic pain management in family practice: a clinical review. 26904479/
ISRN Family Med [Internet]. 2013 Apr 11 [cited 2022 Aug 10];2013:1– 515. Kher V. End-stage renal disease in developing countries. Kidney Int
15. Available from: https://pubmed.ncbi.nlm.nih.gov/24959571/ [Internet]. 2002 [cited 2022 Aug 11];62(1):350–62. Available from:
502. Sadosky A, Schaefer C, Mann R, Bergstrom F, Baik R, Parsons B, https://pubmed.ncbi.nlm.nih.gov/12081600/
et al. Burden of illness associated with painful diabetic peripheral neu- 516. Wetmore JB, Collins AJ. Global challenges posed by the growth of
ropathy among adults seeking treatment in the US: results from a retro- end-stage renal disease. Ren Replace Ther. 2016 Dec 23;2(1):15.
spective chart review and cross-sectional survey. Diabetes Metab Syndr 517. Cade WT. Diabetes-related microvascular and macrovascular dis-
Obes [Internet]. 2013 Feb 7 [cited 2022 Aug 10];6:79–92. Available eases in the physical therapy setting. Phys Ther [Internet]. 2008 [cited
from: https://pubmed.ncbi.nlm.nih.gov/23403729/ 2022 Aug 11];88(11):1322–35. Available from: https://
503. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, pubmed.ncbi.nlm.nih.gov/18801863/
Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a 518. Singh A, Satchell SC. Microalbuminuria: causes and implications.
systematic review and meta-analysis. Lancet Neurol [Internet]. 2015 [cit- Pediatr Nephrol [Internet]. 2011 Nov [cited 2022 Aug 11];26(11):1957–
ed 2022 Aug 10];14(2):16 2–73. Available from: h ttp s:// 65. Available from: https://pubmed.ncbi.nlm.nih.gov/21301888/
pubmed.ncbi.nlm.nih.gov/25575710/ 519. Lozano-Maneiro L, Puente-García A. Renin-Angiotensin-
504. Griebeler ML, Morey-Vargas OL, Brito JP, Tsapas A, Wang Z, Aldosterone System Blockade in Diabetic Nephropathy. Present
Carranza Leon BG, et al. Pharmacologic interventions for painful diabetic Evidences. J Clin Med [Internet]. 2015 Nov 9 [cited 2022
neuropathy: An umbrella systematic review and comparative effective- Aug 11];4(11):1908–37. Available from: https://
ness network meta-analysis. Ann Intern Med [Internet]. 2014 Nov 4 [cit- pubmed.ncbi.nlm.nih.gov/26569322/
ed 2022 Aug 10];161(9):639–49. Available from: https:// 520. Vivian E, Mannebach C. Therapeutic approaches to slowing the
pubmed.ncbi.nlm.nih.gov/25364885/ progression of diabetic nephropathy - is less best? Drugs Context
505. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane [Internet]. 2013 Mar 27 [cited 2022 Aug 11];2013. Available from:
Database Syst Rev [Internet]. 2007 [cited 2022 Aug 10];(4). Available https://pubmed.ncbi.nlm.nih.gov/24432038/
from: https://pubmed.ncbi.nlm.nih.gov/17943857/ 521. Sahay M, Sahay R, Baruah M, Kalra S. Nutrition in chronic kidney
506. Wiffen PJ, Collins S, McQuay HJ, Carroll D, Jadad A, Moore RA. disease. Journal of Medical Nutrition and Nutraceuticals. 2014;3(1):11.
WITHDRAWN. Anticonvulsant drugs for acute and chronic pain. 522. Rigalleau V, Lasseur C, Raffaitin C, Beauvieux MC, Barthe N,
Cochrane Database Syst Rev [Internet]. 2010 Jan 20 [cited 2022 Chauveau P, et al. Normoalbuminuric renal-insufficient diabetic patients:
Aug 10];(1). Available from: https://pubmed.ncbi.nlm.nih.gov/ a lower-risk group. Diabetes Care. 2007 Aug;30(8):2034–9.
20091515/ 523. KDOQI Clinical Practice Guidelines and Clinical Practice
507. AK S, CF N, RC R, JG C, JM C. Diabetic neuropathic pain: Recommendations for Diabetes and Chronic Kidney Disease. Am J
Physiopathology and treatment. World J Diabetes [Internet]. 2015 [cited Kidney Dis [Internet]. 2007 [cited 2022 Aug 11];49(2 Suppl 2).
2022 Aug 10];6(3):432. Available from: https:// Available from: https://pubmed.ncbi.nlm.nih.gov/17276798/
pubmed.ncbi.nlm.nih.gov/25897354/ 524. Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, et al.
508. Herrmann DN, Barbano RL, Hart-Gouleau S, Pennella-Vaughan J, National Kidney Foundation practice guidelines for chronic kidney dis-
Dworkin RH. An open-label study of the lidocaine patch 5% in painful ease: evaluation, classification, and stratification. Ann Intern Med
idiopathic sensory polyneuropathy. Pain Med [Internet]. 2005 Sep [cited [Internet]. 2003 Jul 15 [cited 2022 Aug 11];139(2). Available from:
2022 Aug 10];6(5):379–84. Available from: https:// https://pubmed.ncbi.nlm.nih.gov/12859163/
525. Executive summary: standards of medical care in diabetes–2011. the EMPA-REG OUTCOME® trial. Age Ageing [Internet]. 2019 Nov 1
Diabetes Care [Internet]. 2011 Jan [cited 2022 Aug 11];34 Suppl [cited 2022 Aug 11];48(6):859–66. Available from: https://
1(Suppl 1). Available from: https://pubmed.ncbi.nlm.nih.gov/21193627/ pubmed.ncbi.nlm.nih.gov/31579904/
526. Kumar P, Rao U, Abhilash T, Reddy G. Evaluation of random urine 540. Mosenzon O, Wiviott SD, Cahn A, Rozenberg A, Yanuv I,
sample protein: creatinine ratio as an index of 24 hour urine protein in Goodrich EL, et al. Effects of dapagliflozin on development and progres-
patients with various renal disorders in tertiary care center. International sion of kidney disease in patients with type 2 diabetes: an analysis from
Journal of Advances in Medicine. 2016;855–8. the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol
527. Viswanathan V, Chamukuttan S, Kuniyil S, Ambady R. Evaluation [Internet]. 2019 Aug 1 [cited 2022 Aug 11];7(8):606–17. Available from:
of a simple, random urine test for prospective analysis of proteinuria in https://pubmed.ncbi.nlm.nih.gov/31196815/
Type 2 diabetes: a six year follow-up study. Diabetes Res Clin Pract. 541. Heerspink HJL, Stefánsson B v., Correa-Rotter R, Chertow GM,
2000 Aug;49(2–3):143–7. Greene T, Hou FF, et al. Dapagliflozin in Patients with Chronic Kidney
528. Babu Kondaveeti S, Kumaraswamy D, Mishra S, Aravind Kumar R, Disease. New England Journal of Medicine [Internet]. 2020 Oct 8 [cited
Anand Shaker I. Evaluation of glycated albumin and microalbuminuria as 2022 Aug 21];383(15):1436–46. Available from: https://www.nejm.org/
early risk markers of nephropathy in type 2 diabetes mellitus. J Clin doi/full/10.1056/NEJMoa2024816
Diagn Res [Internet]. 2013 Jul 1 [cited 2022 Aug 11];7(7):1280–3. 542. Tuttle KR, Levin A, Nangaku M, Kadowaki T, Agarwal R, Hauske
Available from: https://pubmed.ncbi.nlm.nih.gov/23998045/ SJ, et al. Safety of Empagliflozin in Patients With Type 2 Diabetes and
529. Jafar TH, Chaturvedi N, Hatcher J, Levey AS. Use of albumin Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical
creatinine ratio and urine albumin concentration as a screening test for Trials. Diabetes Care. 2022 Jun 1;45(6):1445–52.
albuminuria in an Indo-Asian population. Nephrol Dial Transplant 543. Chawla SS, Kaur S, Bharti A, Garg R, Kaur M, Soin D, et al. Impact
[Internet]. 2007 [cited 2022 Aug 11];22(8):2194–200. Available from: of health education on knowledge, attitude, practices and glycemic con-
https://pubmed.ncbi.nlm.nih.gov/17405790/ trol in type 2 diabetes mellitus. J Family Med Prim Care [Internet]. 2019
530. Heathcote KL, Wilson MP, Quest DW, Wilson TW. Prevalence and [cited 2022 Aug 11];8(1):261. Available from: https://
duration of exercise induced albuminuria in healthy people. Clin Invest pubmed.ncbi.nlm.nih.gov/30911517/
Med [Internet]. 2009 Aug [cited 2022 Aug 11];32(4). Available from: 544. Sahay B. Dietary carbohydrate content in Indian diabetic patients.
https://pubmed.ncbi.nlm.nih.gov/19640328/ Medicine . 2012;235–9.
531. SA S, N J. Correlation of random urine protein creatinine (P-C) ratio 545. Viswanathan V, Snehalatha C, Varadharani M. Prevalence of albu-
with 24-hour urine protein and P-C ratio, based on physical activity: a minuria among vegetarian and non-vegetarian south Indian diabetic pa-
pilot study. Ther Clin Risk Manag [Internet]. 2010 Jul [cited 2022 tients. Indian J Nephrol . 2002;73–6.
Aug 11];6:351. Available from: https://pubmed.ncbi.nlm.nih.gov/ 546. Beasley JM, Wylie-Rosett J. The role of dietary proteins among
20856681/ persons with diabetes. Curr Atheroscler Rep. 2013 Sep;15(9):348.
532. Agrawal RP, Ola V, Bishnoi P, Gothwal S, Sirohi P, Agrawal R. 547. Hallan SI, Orth SR. Smoking is a risk factor in the progression to
Prevalence of micro and macrovascular complications and their risk fac- kidney failure. Kidney Int [Internet]. 2011 Sep 1 [cited 2022
tors in type-2 diabetes mellitus. J Assoc Physicians India. 2014 Aug 11];80(5):516–23. Available from: https://
Jun;62(6):504–8. pubmed.ncbi.nlm.nih.gov/21677635/
533. Jadhav UM, Kadam NN. Association of microalbuminuria with 548. SR O. Cigarette smoking: an important renal risk factor - far beyond
carotid intima-media thickness and coronary artery disease–a cross- carcinogenesis. Tob Induc Dis [Internet]. 2002 [cited 2022
sectional study in Western India. J Assoc Physicians India. 2002 Aug 11];1(2):137. Available from: https://pubmed.ncbi.nlm.nih.gov/
Sep;50:1124–9. 19570254/
534. Thampy A, Pais CC. Early Clinical Implications of 549. Shahid SM, Mahboob T. Cigarette smoking: An environmental risk
Microalbuminuria in Patients with Acute Ischaemic Stroke. J Clin factor for progression of nephropathy in diabetes. Int J Diabetes Dev
Diagn Res [Internet]. 2016 Sep 1 [cited 2022 Aug 11];10(9):OC29–31. Ctries. 2007;
Available from: https://pubmed.ncbi.nlm.nih.gov/27790489/ 550. Elihimas Júnior UF, Elihimas HC dos S, Lemos VM, Leão M de A,
535. Chawla R, Zala S, Punyani H, Dhingra J. Correlation between cor- Sá MPB de O, França EET de, et al. Smoking as risk factor for chronic
tical renal thickness and estimated glomerular filtration rate in diabetic kidney disease: systematic review. Jornal Brasileiro de Nefrologia.
nephropathy patients. Journal of Diabetology [Internet]. 2020 [cited 2022 2014;36(4).
Aug 13];11(3):158. Available from: https:// 551. Gupta R, Gupta R, Maheshwari V, Mawliya M. Impact of smoking
www.journalofdiabetology.org/article.asp?issn=2078- on microalbuminuria and urinary albumin creatinine ratio in non-diabetic
7685;year=2020;volume=11;issue=3;spage=158;epage= normotensive smokers. Indian J Nephrol. 2014;24(2):92.
162;aulast=Chawla 552. Varghese A, Deepa R, Rema M, Mohan V. Prevalence of
536. Panchapakesan U, Pollock C. The Role of Dipeptidyl Peptidase - 4 microalbuminuria in type 2 diabetes mellitus at a diabetes centre in south-
Inhibitors in Diabetic Kidney Disease. Front Immunol [Internet]. 2015 ern India. Postgrad Med J [Internet]. 2001 [cited 2022
[cited 2022 Aug 11];6(AUG). Available from: https:// Aug 11];77(908):399–402. Available from: https://
537. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, 553. Thakkar B, Arora K, Vekariya R. Prevalence of microalbuminuria in
Charytan DM, et al. Canagliflozin and Renal Outcomes in Type 2 newly diagnosed type 2 diabetes mellitus. Natl J Integr Res Med.
Diabetes and Nephropathy. N Engl J Med [Internet]. 2019 Jun 13 [cited 2011;22–5.
2022 Aug 11];380(24):2295–306. Available from: https:// 554. Saha TK, Bhattarai AM, Batra HS, Banerjee M, Misra P, Ambade V.
pubmed.ncbi.nlm.nih.gov/30990260/ Correlation of Microalbuminuria with Estimated GFR (eGFR) by
538. Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Erondu N, Cockcroft-Gault and MDRD Formula in Type 2 Diabetics and
Shaw W, et al. Canagliflozin and renal outcomes in type 2 diabetes: Hypertensives. Indian J Clin Biochem [Internet]. 2015 Jul 17 [cited
results from the CANVAS Program randomised clinical trials. Lancet 2022 Aug 11];30(3):271–4. Available from: https://
D i a b e t e s E n d oc r i n o l [ I nt e r n e t ] . 2 0 1 8 S e p 1 [ c i t e d 2 02 2 pubmed.ncbi.nlm.nih.gov/26089611/
Aug 11];6(9):691–704. Available from: https:// 555. Bonakdaran S, Hami M, Hatefi A. The effects of calcitriol on albu-
pubmed.ncbi.nlm.nih.gov/29937267/ minuria in patients with type-2 diabetes mellitus. Saudi J Kidney Dis
539. Monteiro P, Bergenstal RM, Toural E, Inzucchi SE, Zinman B, Transpl [Internet]. 2012 [cited 2022 Aug 11];23(6):1215–20. Available
Hantel S, et al. Efficacy and safety of empagliflozin in older patients in from: https://pubmed.ncbi.nlm.nih.gov/23168851/
556. Filippatos G, Anker SD, Agarwal R, Pitt B, Ruilope LM, Rossing P, 572. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and
et al. Finerenone and Cardiovascular Outcomes in Patients With Chronic Their Recurrence. N Engl J Med [Internet]. 2017 Jun 15 [cited 2022
Kidney Disease and Type 2 Diabetes. Circulation [Internet]. 2021 Feb 9 Aug 11];376(24):2367–75. Available from: https://
www.ahajournals.org/doi/abs/10.1161/ 573. Boulton AJM, Armstrong DG, Kirsner RS, Attinger CE, Lavery LA,
CIRCULATIONAHA.120.051898 Lipsky BA, et al. Diagnosis and Management of Diabetic Foot
557. Abraham S, Jyothylekshmy V, Menon A. Epidemiology of diabetic Complications. Diabetes [Internet]. 2018 [cited 2022
foot complications in a podiatry clinic of a tertiary hospital in South India. Aug 11];2018(2):1–20. Available from: https://
Indian Journal of Health Sciences. 2015;8(1):48. pubmed.ncbi.nlm.nih.gov/30958663/
558. Pendsey SP. Understanding diabetic foot. Int J Diabetes Dev Ctries 574. Kucera T, Shaikh HH, Sponer P. Charcot Neuropathic Arthropathy
[Internet]. 2010 Apr 1 [cited 2022 Aug 11];30(2):75–9. Available from: of the Foot: A Literature Review and Single-Center Experience. J
https://pubmed.ncbi.nlm.nih.gov/20535310/ Diabetes Res [Internet]. 2016 [cited 2022 Aug 11];2016. Available from:
559. Ghosh P, Valia R. Burden of Diabetic Foot Ulcers in India: Evidence https://pubmed.ncbi.nlm.nih.gov/27656656/
Landscape from Published Literature. Value in Health. 2017 575. Rogers LC, Frykberg RG, Armstrong DG, Boulton AJM, Edmonds
Oct;20(9):A485. M, Ha Van G, et al. The Charcot foot in diabetes. Diabetes Care
560. Bhamre SD, Kailash KM, Sadiwala CA. A Clinical Profile of [Internet]. 2011 Sep [cited 2022 Aug 11];34(9):2123–9. Available from:
Diabetic Foot Patients at Tertiary Health Care Institute, Nashik. MVP https://pubmed.ncbi.nlm.nih.gov/21868781/
Journal of Medical Sciences [Internet]. 2015 Jun 1 [cited 2022 576. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat
Aug 13];2(1):49–52. Available from: https:// Med [Internet]. 2000 Apr [cited 2022 Aug 11];6(4):389–95. Available
www.informaticsjournals.com/index.php/mvpjms/article/view/797 from: https://pubmed.ncbi.nlm.nih.gov/10742145/
561. Shobhana R, Rao PR, Lavanya A, Vijay V, Ramachandran A. Foot 577. Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS,
care economics–cost burden to diabetic patients with foot complications: Karchmer AW, et al. Diagnosis and treatment of diabetic foot infections.
a study from southern India. J Assoc Physicians India. 2001 May;49:530– Clin Infect Dis [Internet]. 2004 Oct 1 [cited 2022 Aug 11];39(7):885–
3. 910. Available from: https://pubmed.ncbi.nlm.nih.gov/15472838/
562. Viswanathan V, Thomas N, Tandon N, Asirvatham A, Rajasekar S, 578. Viswanathan V. An aggressive and multi-pronged approach to pre-
Ramachandran A, et al. Profile of diabetic foot complications and its vent amputations in India. Int J Diabetes Dev Ctries. 2014 Sep
associated complications–a multicentric study from India. J Assoc 11;34(3):123–4.
Physicians India. 2005 Nov;53:933–6. 579. Mills JL, Conte MS, Armstrong DG, Pomposelli FB, Schanzer A,
563. Morbach S, Lutale JK, Viswanathan V, Möllenberg J, Ochs HR, Sidawy AN, et al. The Society for Vascular Surgery Lower Extremity
Rajashekar S, et al. Regional differences in risk factors and clinical pre- Threatened Limb Classification System: risk stratification based on
sentation of diabetic foot lesions. Diabet Med [Internet]. 2004 Jan [cited wound, ischemia, and foot infection (WIfI). J Vasc Surg [Internet].
2022 Aug 11];21(1):91–5. Available from: https:// 2014 [cited 2022 Aug 11];59(1). Available from: https://
564. Vijay V BSRA. RSSDI Hand Book of Diabetes Mellitus. Banerjee 580. Viswanathan V, Madhavan S, Rajasekar S, Chamukuttan S,
S, editor. 2016. Ambady R. Amputation prevention initiative in South India: positive
565. Viswanathan V, Kumpatla S. Pattern and causes of amputation in impact of foot care education. Diabetes Care [Internet]. 2005 May [cited
diabetic patients–a multicentric study from India. J Assoc Physicians 2022 Aug 26];28(5):1019–21. Available from: https://
India. 2011 Mar;59:148–51. pubmed.ncbi.nlm.nih.gov/15855560/
566. Viswanathan V, Wadud JR, Madhavan S, Rajasekar S, Kumpatla S, 581. IWGDF Guidelines on the prevention and management of diabetic
Lutale JK, et al. Comparison of post amputation outcome in patients with foot disease IWGDF Guidelines. [cited 2022 Aug 26]; Available from:
type 2 diabetes from specialized foot care centres in three developing www.iwgdfguidelines.org
countries. Diabetes Res Clin Pract [Internet]. 2010 May [cited 2022 582. Afifi L, Abdelalim A, Ashour A, Al-Athwari A. Correlation between
Aug 11];88(2):146–50. Available from: https:// clinical neuropathy scores and nerve conduction studies in patients with
pubmed.ncbi.nlm.nih.gov/20299119/ diabetic peripheral neuropathy. Egypt J Neurol Psychiatr Neurosurg.
567. Viswanathan V, Thomas N, Tandon N, Asirvatham A, Rajasekar S, 2016;53(4):248.
Ramachandran A, et al. Profile of diabetic foot complications and its 583. Kamel SR, Hamdy M, Abo Omar HAS, Kamal A, Ali LH, Abd
associated complications–a multicentric study from India. J Assoc Elkarim AH. Clinical diagnosis of distal diabetic polyneuropathy using
Physicians India. 2005 Nov;53:933–6. neurological examination scores: correlation with nerve conduction stud-
568. Morbach S, Lutale JK, Viswanathan V, Möllenberg J, Ochs HR, ies. Egyptian Rheumatology and Rehabilitation. 2015 Jul 31;42(3):128–
Rajashekar S, et al. Regional differences in risk factors and clinical pre- 36.
sentation of diabetic foot lesions. Diabet Med [Internet]. 2004 Jan [cited 584. Jayaprakash P, Bhansali A, Bhansali S, Dutta P, Anantharaman R,
2022 Aug 11];21(1):91–5. Available from: https:// Shanmugasundar G, et al. Validation of bedside methods in evaluation of
pubmed.ncbi.nlm.nih.gov/14706061/ diabetic peripheral neuropathy. Indian J Med Res. 2011 Jun;133:645–9.
569. Viswanathan V. The diabetic foot: perspectives from Chennai, South 585. Mittal J, Khurana A, Mahajan DS, Dhoat PS. A COMPARATIVE
India. Int J Low Extrem Wounds [Internet]. 2007 Mar [cited 2022 STUDY OF VARIOUS BEDSIDE METHODS IN DETECTION OF
Aug 11];6(1):34–6. Available from: https://pubmed.ncbi.nlm.nih.gov/ DIABETIC POLYNEUROPATHY IN TYPE 2 DIABETES
17344200/ PATIENTS. J Evol Med Dent Sci. 2013 Dec 10;2(50):9702–6.
570. Rastogi A, Dogra H, Jude EB. COVID-19 and peripheral arterial 586. Hussain G, Rizvi SAA, Singhal S, Zubair M, Ahmad J. Cross sec-
complications in people with diabetes and hypertension: A systematic tional study to evaluate the effect of duration of type 2 diabetes mellitus
review. Diabetes & Metabolic Syndrome: Clinical Research & on the nerve conduction velocity in diabetic peripheral neuropathy.
Reviews. 2021 Sep;15(5):102204. Diabetes Metab Syndr. 8(1):48–52.
571. Rastogi A, Hiteshi P, Bhansali A. A, Jude EB. Virtual triage and 587. Dixit S, Maiya A. Diabetic peripheral neuropathy and its evaluation
outcomes of diabetic foot complications during Covid-19 pandemic: A in a clinical scenario: a review. J Postgrad Med. 60(1):33–40.
retro-prospective, observational cohort study. PLoS One. 2021 588. Chawla A, Bhasin GK, Chawla R. Validation Of Neuropathy
May 6;16(5):e0251143. Symptoms Score (NSS) And Neuropathy Disability Score (NDS ) In
The Clinical Diagnosis Of Peripheral Neuropathy In Middle Aged People 606. Ezhilarasi K, Abirami P, Vijay V. Healing effect of hyperbaric
With Diabetes. undefined. 2013; oxygen therapy as an adjunctive treatment on diabetic foot ulcer patients
589. Vijay V, Snehalatha C, Seena R, Ramachandran A. The Rydel in short duration – A brief report. Asian J Sci and Tech. 2018;(9):7743-6.
Seiffer tuning fork: an inexpensive device for screening diabetic patients 607. Armstrong DG, Lavery LA, Bushman TR. Peak foot pressures in-
with high-risk foot. Practical Diabetes International. 2001 Jun;18(5):155– fluence the healing time of diabetic foot ulcers treated with total contact
6. casts. J Rehabil Res Dev. 1998 Jan;35(1):1–5.
590. Viswanathan V, Snehalatha C, Seena R, Ramachandran A. Early 608. Yazdanpanah L, Nasiri M, Adarvishi S. Literature review on the
recognition of diabetic neuropathy: evaluation of a simple outpatient pro- management of diabetic foot ulcer. World J Diabetes. 2015
cedure using thermal perception. Postgrad Med J [Internet]. 2002 Sep 1 Feb 15;6(1):37–53.
[cited 2022 Aug 11];78(923):541–2. Available from: https:// 609. Wu SC, Crews RT, Armstrong DG. The pivotal role of offloading in
pubmed.ncbi.nlm.nih.gov/12357015/ the management of neuropathic foot ulceration. Curr Diab Rep. 2005
591. Vijay V, Seena R, Lalitha S, Snehalatha C, Ramachandran A. A Dec;5(6):423–9.
simple device for foot pressure measurement. Evaluation in south Indian 610. Kari S v. The economical way to off-load diabetic foot ulcers
NIDDM subjects. Diabetes Care. 1998 Jul;21(7):1205–6. [Mandakini off-loading device]. Indian J Surg. 2010 Apr;72(2):133–4.
592. Gnanasundaram S, Ramalingam P, Das BN, Viswanathan V. Gait 611. Agrawal VP. Easy ways to offload diabetic foot ulcer in rural setup.
changes in persons with diabetes: Early risk marker for diabetic foot ulcer. International Journal of Biomedical and Advance Research. 2014
Foot Ankle Surg. 2020 Feb;26(2):163–8. Apr 30;5(4):187.
593. Rajagopalan C, Viswanathan V, Rajsekar S, Selvaraj B, Daniel L. 612. Shankhdhar K. Improvisation is the key to success: the Samadhan
Diabetic foot ulcers—comparison of performance of ankle-brachial index System. Adv Skin Wound Care. 2006 Sep;19(7):379–83.
and transcutaneous partial oxygen pressure in predicting outcome. unde- 613. Liu S, He CZ, Cai YT, Xing QP, Guo YZ, Chen ZL, et al. Evaluation
fined. 2017 Apr 1;38(2):179–84. of negative-pressure wound therapy for patients with diabetic foot ulcers:
594. Abbas ZG. Diabetic Foot - An African Perspective. JSM Foot systematic review and meta-analysis. Ther Clin Risk Manag.
Ankle. 2016;1(1):1005. 2017;13:533–44.
595. Viswanathan V, Madhavan S, Rajasekar S, Chamukuttan S, 614. Viswanathan V, Kesavan R, Vijayan K. Evaluation of Rogers
Ambady R. Amputation prevention initiative in South India: positive Charcot foot classification system in South Indian diabetic subjects with
impact of foot care education. Diabetes Care. 2005 May;28(5):1019–21. Charcot foot. JDiabetic Foot Complications. 2012 Aug;4:67–70.
596. Viswanathan V, Madhavan S, Gnanasundaram S, Gopalakrishna G, 615. Viswanathan V, Madhavan S, Gnanasundaram S, Gopalakrishna G,
Das BN, Rajasekar S, et al. Effectiveness of different types of footwear Das BN, Rajasekar S, et al. Effectiveness of different types of footwear
insoles for the diabetic neuropathic foot: a follow-up study. Diabetes insoles for the diabetic neuropathic foot: a follow-up study. Diabetes
Care. 2004 Feb;27(2):474–7. Care. 2004 Feb;27(2):474–7.
597. Chandalia HB, Singh D, Kapoor V, Chandalia SH, Lamba PS. 616. Richardson JK, Ching C, Hurvitz EA. The relationship between
Footwear and foot care knowledge as risk factors for foot problems in electromyographically documented peripheral neuropathy and falls. J
Indian diabetics. Int J Diabetes Dev Ctries. 2008 Oct;28(4):109–13. Am Geriatr Soc. 1992 Oct;40(10):1008–12.
598. Lipsky BA, Peters EJG, Senneville E, Berendt AR, Embil JM, 617. Wallace C, Reiber GE, LeMaster J, Smith DG, Sullivan K, Hayes S,
Lavery LA, et al. Expert opinion on the management of infections in et al. Incidence of falls, risk factors for falls, and fall-related fractures in
the diabetic foot. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:163–78. individuals with diabetes and a prior foot ulcer. Diabetes Care. 2002
599. Grek CL, Prasad GM, Viswanathan V, Armstrong DG, Gourdie RG, Nov;25(11):1983–6.
Ghatnekar GS. Topical Administration of a Connexin43-based peptide 618. Oliveira PP de, Fachin SM, Tozatti J, Ferreira MC, Marinheiro LPF.
Augments Healing of Chronic Neuropathic Diabetic Foot Ulcers: A Comparative analysis of risk for falls in patients with and without type 2
Multicenter, Randomized Trial. Wound Repair Regen [Internet]. 2015 diabetes mellitus. Rev Assoc Med Bras (1992). 58(2):234–9.
Mar 1 [cited 2022 Sep 15];23(2):203. Available from: /pmc/articles/ 619. Das L, Bhansali A, Prakash M, Jude EB, Rastogi A. Effect of
PMC4472499/ Methylprednisolone or Zoledronic Acid on Resolution of Active
600. Grek CL, Prasad GM, Viswanathan V, Armstrong DG, Gourdie RG, Charcot Neuroarthropathy in Diabetes: A Randomized, Double-Blind,
Ghatnekar GS. Topical administration of a connexin43-based peptide Placebo-Controlled Study. Diabetes Care [Internet]. 2019 Dec 1 [cited
augments healing of chronic neuropathic diabetic foot ulcers: A multi- 2022 Aug 13];42(12):E185–6. Available from: https://
center, randomized trial. Wound Repair Regen. 23(2):203–12. pubmed.ncbi.nlm.nih.gov/31597669/
601. Geethalakshmi Sekkizhar JJ. Bioburden vs. Antibiogram of Diabetic 620. Rastogi A, Bhansali A, Jude EB. Efficacy of medical treatment for
Foot Infection. Clin Res Foot Ankle. 2013;01(03). Charcot neuroarthropathy: a systematic review and meta-analysis of ran-
602. Bonaca MP, Bauersachs RM, Anand SS, Debus ES, Nehler MR, domized controlled trials. Acta Diabetol [Internet]. 2021 Jun 1 [cited
Patel MR, et al. Rivaroxaban in Peripheral Artery Disease after 2022 Aug 13];58(6):687–96. Available from: https://
Revascularization. New England Journal of Medicine. 2020 www.academia.edu/44913959/Efficacy_of_
May 21;382(21):1994–2004. medical_treatment_for_Charcot_neuroarthropathy_a_
603. Bauersachs RM, Szarek M, Brodmann M, Gudz I, Debus ES, Nehler systematic_review_and_meta_analysis_of_randomized_controlled_trials
MR, et al. Total Ischemic Event Reduction With Rivaroxaban After 621. Das L, Rastogi A, Jude EB, Prakash M, Dutta P, Bhansali A. Long-
Peripheral Arterial Revascularization in the VOYAGER PAD Trial. J term foot outcomes following differential abatement of inflammation and
Am Coll Cardiol. 2021 Jul;78(4):317–26. osteoclastogenesis for active Charcot neuroarthropathy in diabetes
604. Anand SS, Caron F, Eikelboom JW, Bosch J, Dyal L, Aboyans V, m el l i tu s. P Lo S On e [ I n t er n e t] . 2 0 2 1 N o v 1 [ ci t e d 2 0 2 2
et al. Major Adverse Limb Events and Mortality in Patients With Aug 13];16(11):e0259224. Available from: https://journals.plos.org/
Peripheral Artery Disease. J Am Coll Cardiol. 2018 May;71(20):2306– plosone/article?id=10.1371/journal.pone.0259224
15. 622. Chaudhary S, Bhansali A, Rastogi A. Mortality in Asian Indians
605. Kaplovitch E, Eikelboom JW, Dyal L, Aboyans V, Abola MT, with Charcot’s neuroarthropathy: a nested cohort prospective study. Acta
Verhamme P, et al. Rivaroxaban and Aspirin in Patients With Diabetol [Internet]. 2019 Dec 1 [cited 2022 Aug 13];56(12):1259–64.
Symptomatic Lower Extremity Peripheral Artery Disease. JAMA Available from: https://pubmed.ncbi.nlm.nih.gov/31187250/
Cardiol. 2020 Sep 30; 623. Rastogi A, Hajela A, Prakash M, Khandelwal N, Kumar R,
Bhattacharya A, et al. Teriparatide (recombinant human parathyroid hor-
mone [1-34]) increases foot bone remodeling in diabetic chronic Charcot
neuroarthropathy: a randomized double-blind placebo-controlled study. J 638. Sosale B, Sosale A, Mohan A, Kumar P, Saboo B, Kandula S.
Diabetes [Internet]. 2019 [cited 2022 Aug 13];11(9):703–10. Available Cardiovascular risk factors, micro and macrovascular complications at
from: https://pubmed.ncbi.nlm.nih.gov/30632290/ diagnosis in patients with young onset type 2 diabetes in India: CINDI
624. Rastogi A, Prakash M, Bhansali A. Varied presentations and out- 2. Indian J Endocrinol Metab [Internet]. 2016 Jan 1 [cited 2022
comes of Charcot neuroarthropathy in patients with diabetes mellitus. Int Aug 12];20(1):114–8. Available from: https://pubmed.ncbi.nlm.nih.gov/
J Diabetes Dev Ctries. 2019 Jul 14;39(3):513–22. 26904479/
625. Petrova NL, Donaldson NK, Bates M, Tang W, Jemmott T, Morris 639. O’Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H,
V, et al. Effect of Recombinant Human Parathyroid Hormone (1-84) on et al. Global and regional effects of potentially modifiable risk factors
Resolution of Active Charcot Neuro-osteoarthropathy in Diabetes: A associated with acute stroke in 32 countries (INTERSTROKE): a case-
Randomized, Double-Blind, Placebo-Controlled Study. Diabetes Care. control study. Lancet [Internet]. 2016 Aug 20 [cited 2022
2021 Jul 1;44(7):1613–21. Aug 12];388(10046):761–75. Available from: https://
626. Busch-Westbroek TE, Delpeut K, Balm R, Bus SA, Schepers T, pubmed.ncbi.nlm.nih.gov/27431356/
Peters EJ, et al. Effect of Single Dose of RANKL Antibody Treatment 640. Yusuf PS, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, et al.
on Acute Charcot Neuro-osteoarthropathy of the Foot. Diabetes Care Effect of potentially modifiable risk factors associated with myocardial
[Internet]. 2018 Mar 1 [cited 2022 Aug 13];41(3):e21–2. Available from: infarction in 52 countries (the INTERHEART study): case-control study.
https://pubmed.ncbi.nlm.nih.gov/29273577/ Lancet [Internet]. 2004 Sep 11 [cited 2022 Aug 12];364(9438):937–52.
627. Hung YC, Chiu LT, Huang HY, Bau DT. Pioglitazone for primary Available from: https://pubmed.ncbi.nlm.nih.gov/15364185/
stroke prevention in Asian patients with type 2 diabetes and cardiovascu- 641. Gant CM, Mensink I, Heleen Binnenmars S, van der Palen JAM,
lar risk factors: a retrospective study. Cardiovasc Diabetol. Bakker SJL, Navis G, et al. Body weight course in the DIAbetes and
2020;19(1):94. LifEstyle Cohort Twente (DIALECT-1)—A 20-year observational study.
628. Spence JD, Viscoli CM, Inzucchi SE, Dearborn-Tomazos J, Ford PLoS One [Internet]. 2019 Jun 1 [cited 2022 Aug 12];14(6):e0218400.
GA, Gorman M, et al. Pioglitazone Therapy in Patients With Stroke and Available from: https://journals.plos.org/plosone/article?id=10.1371/
Prediabetes. JAMA Neurol. 2019 May 1;76(5):526. journal.pone.0218400
629. DeFronzo RA, Inzucchi S, Abdul-Ghani M, Nissen SE. 642. Mortada I. Hyperuricemia, Type 2 Diabetes Mellitus, and
Pioglitazone: The forgotten, cost-effective cardioprotective drug for type Hypertension: an Emerging Association. Curr Hypertens Rep [Internet].
2 diabetes. Diab Vasc Dis Res. 2019 Mar 1;16(2):133–43. 2017 Sep 1 [cited 2022 Aug 12];19(9). Available from: https://
630. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin pubmed.ncbi.nlm.nih.gov/28770533/
MM, et al. 2022 AHA/ACC/HFSA Guideline for the Management of 643. Hippisley-Cox J, Coupland C, Brindle P. Development and valida-
Heart Failure: A Report of the American College of Cardiology/ tion of QRISK3 risk prediction algorithms to estimate future risk of car-
American Heart Association Joint Committee on Clinical Practice diovascular disease: prospective cohort study. BMJ [Internet]. 2017
Guidelines. Circulation [Internet]. 2022 May 3 [cited 2022 May 23 [cited 2022 Aug 12];357. Available from: https://
Aug 21];145(18):E895–1032. Available from: https:// www.bmj.com/content/357/bmj.j2099
www.ahajournals.org/doi/abs/10.1161/CIR.0000000000001063 644. Robson J, Hippisley-Cox J, Coupland C. QRISK or Framingham?
631. Hsu CY, Lee CM, Chou KY, Lee CY, Chen HC, Chiou JY, et al. Br J Clin Pharmacol [Internet]. 2012 Sep [cited 2022 Aug 12];74(3):545.
The Association of Diabetic Retinopathy and Cardiovascular Disease: A Available from: /pmc/articles/PMC3477356/
13-Year Nationwide Population-Based Cohort Study. Int J Environ Res 645. Stevens RJ, Kothari V, Adler AI, Stratton IM, United Kingdom
Public Health [Internet]. 2021 Aug 1 [cited 2022 Aug 12];18(15). Prospective Diabetes Study (UKPDS) Group. The UKPDS risk engine:
Available from: /pmc/articles/PMC8345672/ a model for the risk of coronary heart disease in Type II diabetes (UKPDS
632. I MT, C SC, A SG, FJ DCG. Type 2 diabetes and cardiovascular 56). Clin Sci (Lond). 2001 Dec;101(6):671–9.
disease: Have all risk factors the same strength? World J Diabetes 646. Khunti K, Chen H, Cid-Ruzafa J, Fenici P, Gomes MB, Hammar N,
[Internet]. 2014 [cited 2022 Aug 12];5(4):444. Available from: https:// et al. Glycaemic control in patients with type 2 diabetes initiating second-
pubmed.ncbi.nlm.nih.gov/25126392/ line therapy: Results from the global DISCOVER study programme.
633. Association AD. 8. Cardiovascular Disease and Risk Management. Diabetes Obes Metab [Internet]. 2020 Jan 1 [cited 2022
Diabetes Care [Internet]. 2016 Jan 1 [cited 2022 Aug 12];22(1):66–78. Available from: https://onlinelibrary.wiley.com/
Aug 12];39(Supplement_1):S60–71. Available from: https:// doi/full/10.1111/dom.13866
diabetesjournals.org/care/article/39/Supplement_1/S60/28772/8- 647. Chandra KS, Bansal M, Nair T, Iyengar SS, Gupta R, Manchanda
Cardiovascular-Disease-and-Risk-Management SC, et al. Consensus statement on management of dyslipidemia in Indian
634. Cai X, Liu X, Sun L, He Y, Zheng S, Zhang Y, et al. Prediabetes and subjects. Indian Heart J [Internet]. 2014 Dec 1 [cited 2022
the risk of heart failure: A meta-analysis. Diabetes Obes Metab [Internet]. Aug 12];66(Suppl 3):S1. Available from: /pmc/articles/PMC4297876/
2021 Aug 1 [cited 2022 Aug 12];23(8):1746–53. Available from: https:// 648. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano
pubmed.ncbi.nlm.nih.gov/33769672/ AL, et al. 2016 European Guidelines on cardiovascular disease preven-
635. Prabhakaran D, Jeemon P, Roy A. Cardiovascular Diseases in India: tion in clinical practice: The Sixth Joint Task Force of the European
Current Epidemiology and Future Directions. Circulation [Internet]. 2016 Society of Cardiology and Other Societies on Cardiovascular Disease
Apr 19 [cited 2022 Aug 12];133(16):1605–20. Available from: https:// Prevention in Clinical Practice (constituted by representatives of 10 soci-
pubmed.ncbi.nlm.nih.gov/27142605/ eties and by invited experts)Developed with the special contribution of
636. Gupta A, Gupta R, Sharma KK, Lodha S, Achari V, Asirvatham AJ, the European Association for Cardiovascular Prevention & Rehabilitation
et al. Prevalence of diabetes and cardiovascular risk factors in middle- (EACPR). Eur Heart J [Internet]. 2016 Aug 1 [cited 2022
class urban participants in India. BMJ Open Diabetes Res Care [Internet]. Aug 12];37(29):2315–81. Available from: https://
2014 Dec 1 [cited 2022 Aug 12];2(1):e000048. Available from: https:// pubmed.ncbi.nlm.nih.gov/27222591/
drc.bmj.com/content/2/1/e000048 649. Dehghan M, Mente A, Zhang X, Swaminathan S, Li W, Mohan V,
637. Sosale A, Prasanna Kumar K, Sadikot S, Nigam A, Bajaj S, Zargar et al. Associations of fats and carbohydrate intake with cardiovascular
A, et al. Chronic complications in newly diagnosed patients with Type 2 disease and mortality in 18 countries from five continents (PURE): a
diabetes mellitus in India. Indian J Endocrinol Metab [Internet]. 2014 prospective cohort study. Lancet [Internet]. 2017 Nov 1 [cited 2022
May 1 [cited 2022 Aug 12];18(3):355–60. Available from: https:// Aug 12];390(10107):2050–62. Available from: https://
650. Gray A, Threlkeld RJ. Nutritional Recommendations for Individuals Aug 12];297(3):286–94. Available from: https://
with Diabetes. 2000. pubmed.ncbi.nlm.nih.gov/17227980/
651. Varghese T, Schultz WM, McCue AA, Lambert CT, Sandesara PB, 665. Knopp RH, D’Emden M, Smilde JG, Pocock SJ. Efficacy and safety
Eapen DJ, et al. Physical activity in the prevention of coronary heart of atorvastatin in the prevention of cardiovascular end points in subjects
disease: implications for the clinician. Heart [Internet]. 2016 Jun 15 [cited with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary
2022 Aug 12];102(12):904–9. Available from: https:// Heart Disease Endpoints in non-insulin-dependent diabetes mellitus
pubmed.ncbi.nlm.nih.gov/26941396/ (ASPEN). Diabetes Care [Internet]. 2006 [cited 2022
652. Buttar HS, Li T, Ravi N. Prevention of cardiovascular diseases: Role Aug 12];29(7):1478–85. Available from: https://
of exercise, dietary interventions, obesity and smoking cessation. Exp pubmed.ncbi.nlm.nih.gov/16801565/
Clin Cardiol. 2005;10(4):229–49. 666. Macchia A, Laffaye N, Comignani PD, Cornejo Pucci E, Igarzabal
653. Steptoe A, Kivimäki M. Stress and cardiovascular disease. Nat Rev C, Scazziota AS, et al. Statins but Not Aspirin Reduce Thrombotic Risk
Cardiol [Internet]. 2012 Jun [cited 2022 Aug 12];9(6):360–70. Available Assessed by Thrombin Generation in Diabetic Patients without
from: https://pubmed.ncbi.nlm.nih.gov/22473079/ Cardiovascular Events: The RATIONAL Trial. PLoS One [Internet].
654. Gulliksson M, Burell G, Vessby B, Lundin L, Toss H, Svärdsudd K. 2012 Mar 28 [cited 2022 Aug 12];7(3):e32894. Available from: https://
Randomized controlled trial of cognitive behavioral therapy vs standard journals.plos.org/plosone/article?id=10.1371/journal.pone.0032894
treatment to prevent recurrent cardiovascular events in patients with cor- 667. Shepherd J, Barter P, Carmena R, Deedwania P, Fruchart JC,
onary heart disease: Secondary Prevention in Uppsala Primary Health Haffner S, et al. Effect of lowering LDL cholesterol substantially below
Care project (SUPRIM). Arch Intern Med [Internet]. 2011 Jan 24 [cited currently recommended levels in patients with coronary heart disease and
2022 Aug 12];171(2):134–40. Available from: https:// diabetes: the Treating to New Targets (TNT) study. Diabetes Care
pubmed.ncbi.nlm.nih.gov/21263103/ [Internet]. 2006 [cited 2022 Aug 12];29(6):1220–6. Available from:
655. Richards SH, Anderson L, Jenkinson CE, Whalley B, Rees K, https://pubmed.ncbi.nlm.nih.gov/16731999/
Davies P, et al. Psychological interventions for coronary heart disease: 668. de Vries FM, Kolthof J, Postma MJ, Denig P, Hak E. Efficacy of
Cochrane systematic review and meta-analysis. Eur J Prev Cardiol Standard and Intensive Statin Treatment for the Secondary Prevention of
[Internet]. 2018 Feb 1 [cited 2022 Aug 12];25(3):247–59. Available Cardiovascular and Cerebrovascular Events in Diabetes Patients: A Meta-
from: https://pubmed.ncbi.nlm.nih.gov/29212370/ Analysis. PLoS On e [Intern et]. 2014 Nov 5 [cited 2022
656. Malik P, Dwivedi S. Diabetes and cardiovascular diseases. JIMSA. Aug 12];9(11):e111247. Available from: https://journals.plos.org/
2015;61–3. plosone/article?id=10.1371/journal.pone.0111247
657. L B, M M, K W, W S, G B, J B, et al. Effects of Aspirin for Primary 669. Enas EA, Kuruvila A, Khanna P, Pitchumoni CS, Mohan V.
Prevention in Persons with Diabetes Mellitus. N Engl J Med [Internet]. Benefits & risks of statin therapy for primary prevention of cardiovascular
2018 Oct 18 [cited 2022 Aug 12];379(16):1529–39. Available from: disease in Asian Indians – A population with the highest risk of premature
https://pubmed.ncbi.nlm.nih.gov/30146931/ coronary artery disease & diabetes. Indian J Med Res [Internet]. 2013 Oct
658. Xie M, Shan Z, Zhang Y, Chen S, Yang W, Bao W, et al. Aspirin for [cited 2022 Aug 12];138(4):461. Available from: /pmc/articles/
primary prevention of cardiovascular events: meta-analysis of random- PMC3868060/
ized controlled trials and subgroup analysis by sex and diabetes status. 670. Gupta R, Lodha S, Sharma KK, Sharma SK, Gupta S, Asirvatham
PLoS One [Internet]. 2014 Oct 31 [cited 2022 Aug 12];9(10). Available AJ, et al. Evaluation of statin prescriptions in type 2 diabetes: India Heart
from: https://pubmed.ncbi.nlm.nih.gov/25360605/ Watch-2. BMJ Open Diabetes Res Care [Internet]. 2016 Aug 1 [cited
659. Guirguis-Blake JM, Evans C v, Senger CA, Rowland MG, 2022 Aug 12];4(1). Available from: https://pubmed.ncbi.nlm.nih.gov/
O’Connor EA, Whitlock EP. Aspirin for the Primary Prevention of 27648292/
Cardiovascular Events. Aspirin for the Primary Prevention of 671. Doggrell S. Is atorvastatin superior to other statins? Analysis of the
Cardiovascular Events: A Systematic Evidence Review for the US clinical trials with atorvastatin having cardiovascular endpoints. Rev
Preventive Services Task Force [Internet]. 2015 [cited 2022 Aug 12]; Re cent C lin Tri als [Int ernet] . 2006 Ma y 1 3 [c ite d 2 022
Available from: https://www.ncbi.nlm.nih.gov/books/NBK321623/ Aug 12];1(2):143–53. Available from: https://pubmed.ncbi.nlm.nih.gov/
660. Kokoska LA, Wilhelm SM, Garwood CL, Berlie HD. Aspirin for 18473965/
primary prevention of cardiovascular disease in patients with diabetes: A 672. Sharp PS, Mohan V, Levy JC, Mather HM, Kohner EM. Insulin
meta-analysis. Diabetes Res Clin Pract [Internet]. 2016 Oct 1 [cited 2022 resistance in patients of Asian Indian and European origin with non-
Aug 12];120:31–9. Available from: https://pubmed.ncbi.nlm.nih.gov/ insulin dependent diabetes. Horm Metab Res [Internet]. 1987 [cited
27500549/ 2022 Aug 12];19(2):84–5. Available from: https://
661. Collins R, Peto R, Hennekens C, Doll R, Bubes V, Buring J, et al. pubmed.ncbi.nlm.nih.gov/3549505/
Aspirin in the primary and secondary prevention of vascular disease: 673. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA,
collaborative meta-analysis of individual participant data from Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute
randomised trials. Lancet [Internet]. 2009 May 30 [cited 2022 Coronary Syndromes. N Engl J Med [Internet]. 2015 Jun 18 [cited
Aug 12];373(9678):1849–60. Available from: https:// 2022 Aug 12];372(25):2387–97. Available from: https://
662. Tufano A, Cimino E, di Minno MND, Ieranò P, Marrone E, 674. Foody JAM, Toth PP, Tomassini JE, Sajjan S, Ramey DR, Neff D,
Strazzullo A, et al. Diabetes mellitus and cardiovascular prevention: the et al. Changes in LDL-C levels and goal attainment associated with ad-
role and the limitations of currently available antiplatelet drugs. Int J Vasc dition of ezetimibe to simvastatin, atorvastatin, or rosuvastatin compared
Med [Internet]. 2011 [cited 2022 Aug 12];2011. Available from: https:// with titrating statin monotherapy. Vasc Health Risk Manag [Internet].
pubmed.ncbi.nlm.nih.gov/21761004/ 2013 [cited 2022 Aug 12];9(1):719–27. Available from: https://
663. Squizzato A, Keller T, Romualdi E, Middeldorp S. Clopidogrel plus pubmed.ncbi.nlm.nih.gov/24265554/
aspirin versus aspirin alone for preventing cardiovascular disease. 675. A K, RJ S, P B, J B, R S, MR T, et al. Effects of long-term
Cochrane Database Syst Rev [Internet]. 2011 Jan 19 [cited 2022 fenofibrate therapy on cardiovascular events in 9795 people with type 2
Aug 12];(1). Available from: https://pubmed.ncbi.nlm.nih.gov/ diabetes mellitus (the FIELD study): randomised controlled trial. Lancet
21249668/ [Internet]. 2005 Nov 26 [cited 2022 Aug 12];366(9500):1849–61.
664. Joshi P, Islam S, Pais P, Reddy S, Dorairaj P, Kazmi K, et al. Risk Available from: https://pubmed.ncbi.nlm.nih.gov/16310551/
factors for early myocardial infarction in South Asians compared with 676. Zhu L, Hayen A, Bell KJL. Legacy effect of fibrate add-on therapy
individuals in other countries. JAMA [Internet]. 2007 Jan 17 [cited 2022 in diabetic patients with dyslipidemia: A secondary analysis of the
ACCORDION study. Cardiovasc Diabetol [Internet]. 2020 Mar 5 [cited Aug 12];370(9590):829–40. Available from: https://
2022 Aug 12];19(1):1–9. Available from: https:// pubmed.ncbi.nlm.nih.gov/17765963/
cardiab.biomedcentral.com/articles/10.1186/s12933-020-01002-x 690. Joshi S. Anjana RM, Siddiqui MK, Jebarani S, Vignesh MA, Kamal
677. Goldfine AB, Kaul S, Hiatt WR. Fibrates in the Treatment of Raj N, Unnikrishnan R, Pradeepa R, Panikar VK, Kesavadev J, Saboo B,
Dyslipidemias — Time for a Reassessment. New England Journal of Gupta S, Sosale AR, Seshadri KG, Deshpande N, Chawla M, Chawla P,
Medicine [Internet]. 2011 Aug 11 [cited 2022 Aug 12];365(6):481–4. Das S, Behera M, Chawla R, Nigam A, Gupta A, Kovil R, Joshi SR,
Available from: https://www.nejm.org/doi/full/10.1056/nejmp1106688 Agarwal S, Bajaj S, Pearson ER, Doney ASF, Palmer CNA, Mohan V.
678. Chaudhary R, Garg J, Shah N, Sumner A. PCSK9 inhibitors: A new Prescribing Patterns and Response to Antihyperglycemic Agents Among
era of lipid lowering therapy. World J Cardiol [Internet]. 2017 [cited 2022 Novel Clusters of Type 2 Diabetes in Asian Indians. 2022 Aug;
Aug 12];9(2):76. Available from: https://pubmed.ncbi.nlm.nih.gov/ 691. Joshi SR, Yeolekar ME, Tripathi KK, Giri J, Maity AK, Chopda M,
28289523/ et al. Evaluation of efficacy and tolerability of Losartan and Ramipril
679. Ray KK, Seshasai SRK, Wijesuriya S, Sivakumaran R, Nethercott S, combination in the management of hypertensive patients with associated
Preiss D, et al. Effect of intensive control of glucose on cardiovascular diabetes mellitus in India (LORD Trial). J Assoc Physicians India. 2004
outcomes and death in patients with diabetes mellitus: a meta-analysis of Mar;52:189–95.
randomised controlled trials. The Lancet [Internet]. 2009 [cited 2022 692. Pareek A, Chandurkar NB, Sharma R, Tiwari D, Gupta BS. Efficacy
Aug 12];373(9677):1765–72. Available from: https:// and tolerability of a fixed-dose combination of metoprolol extended
www.ncbi.nlm.nih.gov/books/NBK77956/ release/amlodipine in patients with mild-to-moderate hypertension: a ran-
680. Palmer SC, Mavridis D, Nicolucci A, Johnson DW, Tonelli M, domized, parallel-group, multicentre comparison with losartan plus
Craig JC, et al. Comparison of Clinical Outcomes and Adverse Events amlodipine. Clin Drug Investig [Internet]. 2010 [cited 2022
Associated With Glucose-Lowering Drugs in Patients With Type 2 Aug 12];30(2):123–31. Available from: https://
Diabetes: A Meta-analysis. JAMA [Internet]. 2016 Jul 19 [cited 2022 pubmed.ncbi.nlm.nih.gov/20067330/
Aug 12];316(3):313–24. Available from: https:// 693. Rao NS, Oomman A, Bindumathi PL, Sharma V, Rao S,
pubmed.ncbi.nlm.nih.gov/27434443/ Moodahadu LS, et al. Efficacy and tolerability of fixed dose combination
681. McMurray JJV, Ponikowski P, Bolli GB, Lukashevich V, Kozlovski of metoprolol and amlodipine in Indian patients with essential hyperten-
P, Kothny W, et al. Effects of Vildagliptin on Ventricular Function in sion. J Midlife Health [Internet]. 2013 [cited 2022 Aug 12];4(3):160.
Patients With Type 2 Diabetes Mellitus and Heart Failure: A Randomized Available from: /pmc/articles/PMC3952407/
Placebo-Controlled Trial. JACC Heart Fail [Internet]. 2018 Jan 1 [cited 694. Testa R, Bonfigli AR, Prattichizzo F, la Sala L, de Nigris V, Ceriello
2022 Aug 12];6(1):8–17. Available from: https://clinicaltrials.gov/ct2/ A. The “metabolic memory” theory and the early treatment of hypergly-
show/NCT00894868 cemia in prevention of diabetic complications. Nutrients . 2017;
682. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, 695. Gæde P, Oellgaard J, Carstensen B, Rossing P, Lund-Andersen H,
et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. Parving HH, et al. Years of life gained by multifactorial intervention in
New England Journal of Medicine [Internet]. 2021 Oct 14 [cited 2022 patients with type 2 diabetes mellitus and microalbuminuria: 21 years
Aug 12];385(16):1451–61. Available from: https://www.nejm.org/doi/ follow-up on the Steno-2 randomised trial. Diabetologia [Internet].
full/10.1056/NEJMoa2107038 2016 Nov 1 [cited 2022 Aug 12];59(11):2298–307. Available from:
683. Linagliptin and Glimepiride Have Comparable Cardiovascular https://pubmed.ncbi.nlm.nih.gov/27531506/
Safety Effects in Type 2 Diabetes at High Cardiovascular Risk | ADA 696. Gerstein HC, Sattar N, Rosenstock J, Ramasundarahettige C, Pratley
[Internet]. [cited 2022 Aug 12]. Available from: https://diabetes.org/ R, Lopes RD, et al. Cardiovascular and Renal Outcomes with
newsroom/press-releases/2019/linagliptin-and-glimepiride Efpeglenatide in Type 2 Diabetes. New England Journal of Medicine
684. Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, [Internet]. 2021 Sep 2 [cited 2022 Aug 12];385(10):896–907. Available
Jarolim P, et al. Heart failure, saxagliptin, and diabetes mellitus: observa- from: https://www.nejm.org/doi/full/10.1056/NEJMoa2108269
tions from the SAVOR-TIMI 53 randomized trial. Circulation [Internet]. 697. Farooqui KJ, Mithal A, Kerwen AK, Chandran M. Type 2 diabetes
2014 [cited 2022 Aug 12];130(18):1579–88. Available from: https:// and bone fragility- An under-recognized association. Diabetes Metab
pubmed.ncbi.nlm.nih.gov/25189213/ Syndr. 15(3):927–35.
685. Karagiannis T, Bekiari E, Boura P, Tsapas A. Cardiovascular risk 698. Ferrari SL, Abrahamsen B, Napoli N, Akesson K, Chandran M,
with DPP-4 inhibitors: latest evidence and clinical implications. Ther Adv Eastell R, et al. Diagnosis and management of bone fragility in diabetes:
Drug Saf [Internet]. 2016 Apr 1 [cited 2022 Aug 12];7(2):36. Available an emerging challenge. Osteoporos Int. 2018 Dec;29(12):2585–96.
from: /pmc/articles/PMC4785858/ 699. Kaur P, Anjana RM, Tandon N, Singh MK, Mohan V, Mithal A.
686. WC C, GW E, RP B, DC G, RH G, JA C, et al. Effects of intensive Increased prevalence of self-reported fractures in Asian Indians with di-
blood-pressure control in type 2 diabetes mellitus. N Engl J Med abetes: Results from the ICMR-INDIAB population based cross-sectional
[Internet]. 2010 Apr 29 [cited 2022 Aug 12];362(17):1575–85. study. Bone [Internet]. 2020 Jun 1 [cited 2022 Sep 1];135. Available
Available from: https://pubmed.ncbi.nlm.nih.gov/20228401/ from: https://pubmed.ncbi.nlm.nih.gov/32200024/
687. Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure 700. Dhibar DP, Gogate Y, Aggarwal S, Garg S, Bhansali A, Bhadada
lowering on outcome incidence in hypertension: 7. Effects of more vs. SK. Predictors and Outcome of Fragility Hip Fracture: A Prospective
less intensive blood pressure lowering and different achieved blood pres- Study from North India. Indian J Endocrinol Metab [Internet]. 2019 [cited
sure levels - updated overview and meta-analyses of randomized trials. J 2022 Aug 13];23(3):282. Available from: /pmc/articles/PMC6683687/
Hypertens [Internet]. 2016 Apr 1 [cited 2022 Aug 12];34(4):613–22. 701. Chawla J, Sharma N, Arora D, Arora M, Shukla L. Bone densitom-
Available from: https://pubmed.ncbi.nlm.nih.gov/26848994/ etry status and its associated factors in peri and post menopausal females:
688. Bangalore S, Kumar S, Volodarskiy A, Messerli FH. Blood pressure A cross sectional study from a tertiary care centre in India. Taiwan J
targets in patients with coronary artery disease: observations from tradi- Obstet Gynecol. 2018 Feb;57(1):100–5.
tional and Bayesian random effects meta-analysis of randomised trials. 702. Agarwal K, Cherian KE, Kapoor N, Paul T v. OSTA as a screening
Heart [Internet]. 2013 May [cited 2022 Aug 12];99(9):601–13. Available tool to predict osteoporosis in Indian postmenopausal women — a na-
from: https://pubmed.ncbi.nlm.nih.gov/22914531/ tionwide study. Archives of Osteoporosis 2022 17:1 [Internet]. 2022 Sep
689. A P, S M, J C, B N, M W, L B, et al. Effects of a fixed combination 10 [cited 2022 Sep 15];17(1):1–7. Available from: https://
of perindopril and indapamide on macrovascular and microvascular out- link.springer.com/article/10.1007/s11657-022-01159-w
comes in patients with type 2 diabetes mellitus (the ADVANCE trial): a 703. Sihota P, Yadav RN, Dhaliwal R, Bose JC, Dhiman V, Neradi D,
randomised controlled trial. Lancet [Internet]. 2007 Sep 8 [cited 2022 et al. Investigation of Mechanical, Material, and Compositional
Determinants of Human Trabecular Bone Quality in Type 2 Diabetes. J Aug 9];93(11 Suppl 1). Available from: https://
Clin Endocrinol Metab [Internet]. 2021 May 1 [cited 2022 Sep pubmed.ncbi.nlm.nih.gov/18987276/
15];106(5):E2271–89. Available from: https:// 719. Ahirwar R, Mondal PR. Prevalence of obesity in India: A systematic
pubmed.ncbi.nlm.nih.gov/33475711/ review. Diabetes Metab Syndr [Internet]. 2019 Jan 1 [cited 2022
704. Chawla J, Sharma N, Arora D, Arora M, Shukla L. Bone densitom- Aug 9];13(1):318–21. Available from: https://pubmed.ncbi.nlm.nih.gov/
etry status and its associated factors in peri and post menopausal females: 30641719/
A cross sectional study from a tertiary care centre in India. Taiwan J 720. Ramachandran A, Snehalatha C, Viswanathan V, Viswanathan M,
Obstet Gynecol. 2018 Feb;57(1):100–5. Haffner SM. Risk of noninsulin dependent diabetes mellitus conferred by
705. Dhibar DP, Gogate Y, Aggarwal S, Garg S, Bhansali A, Bhadada obesity and central adiposity in different ethnic groups: A comparative
SK. Predictors and Outcome of Fragility Hip Fracture: A Prospective analysis between Asian Indians, Mexican Americans and Whites.
Study from North India. Indian J Endocrinol Metab [Internet]. 2019 [cited Diabetes Res Clin Pract. 1997 May 1;36(2):121–5.
2022 Aug 13];23(3):282. Available from: /pmc/articles/PMC6683687/ 721. Misra A, Khurana L. The metabolic syndrome in South Asians:
706. Vieira Barbosa J, Lai M. Nonalcoholic Fatty Liver Disease epidemiology, determinants, and prevention. Metab Syndr Relat Disord
Screening in Type 2 Diabetes Mellitus Patients in the Primary Care [Internet]. 2009 Dec 1 [cited 2022 Aug 9];7(6):497–514. Available from:
Setting. Hepatol Commun [Internet]. 2021 Feb 1 [cited 2022 Sep https://pubmed.ncbi.nlm.nih.gov/19900153/
15];5(2):158–67. Available from: https://onlinelibrary.wiley.com/doi/ 722. Misra A, Vikram NK, Gupta R, Pandey RM, Wasir JS, Gupta VP.
full/10.1002/hep4.1618 Waist circumference cutoff points and action levels for Asian Indians for
707. Kuchay MS, Choudhary NS, Mishra SK, Bano T, Gagneja S, identification of abdominal obesity. Int J Obes (Lond) [Internet]. 2006 Jan
Mathew A, et al. Prevalence of clinically relevant liver fibrosis due to [cited 2022 Aug 9];30(1):106–11. Available from: https://
nonalcoholic fatty liver disease in Indian individuals with type 2 diabetes. pubmed.ncbi.nlm.nih.gov/16189502/
JGH Open. 2021 Aug;5(8):915–22. 723. (PDF) Obesity is becoming synonym for diabetes in rural areas of
708. Kuchay MS, Choudhary NS, Gagneja S, Mathew A, Bano T, Kaur india also an alarming situation [Internet]. [cited 2022 Aug 9]. Available
P, et al. Low skeletal muscle mass is associated with liver fibrosis in from: https://www.researchgate.net/publication
individuals with type 2 diabetes and nonalcoholic fatty liver disease. J /228988488_Obesity_is_becoming_synonym_for_
Gastroenterol Hepatol. 2021 Nov;36(11):3204–11. diabetes_in_rural_areas_of_india_also_an_alarming_situation
709. Kuchay MS, Krishan S, Mishra SK, Choudhary NS, Singh MK, 724. Mohan V, Sharp PS, Cloke HR, Burrin JM, Schumer B, Kohner
Wasir JS, et al. Effect of dulaglutide on liver fat in patients with type 2 EM. Serum immunoreactive insulin responses to a glucose load in Asian
diabetes and NAFLD: randomised controlled trial (D-LIFT trial). Indian and European type 2 (non-insulin-dependent) diabetic patients and
Diabetologia. 2020;63(11):2434–45. control subjects. Diabetologia [Internet]. 1986 Apr [cited 2022
710. Kuchay MS, Krishan S, Mishra SK, Farooqui KJ, Singh MK, Wasir Aug 9];29(4):235–7. Available from: https://pubmed.ncbi.nlm.nih.gov/
JS, et al. Effect of Empagliflozin on Liver Fat in Patients With Type 2 3519338/
Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized 725. Sharp PS, Mohan V, Levy JC, Mather HM, Kohner EM. Insulin
Controlled Trial (E-LIFT Trial). Diabetes Care. 2018;41(8):1801–8. resistance in patients of Asian Indian and European origin with non-
711. Ghosh A, Dutta K, Bhatt SP, Gupta R, Tyagi K, Ansari IA, et al. insulin dependent diabetes. Horm Metab Res [Internet]. 1987 [cited
Dapagliflozin Improves Body Fat Patterning, and Hepatic and Pancreatic 2022 Aug 9];19(2):84–5. Available from: https://
Fat in Patients With Type 2 Diabetes in North India. J Clin Endocrinol pubmed.ncbi.nlm.nih.gov/3549505/
Metab. 2022;107(6):e2267–75. 726. Snehalatha C, Viswanathan V, Ramachandran A. Cutoff values for
712. Gulati S, Misra A. Abdominal obesity and type 2 diabetes in Asian normal anthropometric variables in asian Indian adults. Diabetes Care
Indians: dietary strategies including edible oils, cooking practices and [Internet]. 2003 May 1 [cited 2022 Aug 9];26(5):1380–4. Available from:
sugar intake. Eur J Clin Nutr [Internet]. 2017 Jun 14 [cited 2022 https://pubmed.ncbi.nlm.nih.gov/12716792/
Aug 9];71(7):850–7. Available from: https://europepmc.org/article/med/ 727. Diabetes & obesity – the Indian angle - PubMed [Internet]. [cited
28612831 2022 Aug 9]. Available from: https://pubmed.ncbi.nlm.nih.gov/
713. Haslam DW, James WPT. Obesity. Lancet [Internet]. 2005 Oct 1 15591626/
[cited 2022 Aug 9];366(9492):1197–209. Available from: https:// 728. Kaur J. A comprehensive review on metabolic syndrome. Cardiol
pubmed.ncbi.nlm.nih.gov/16198769/ Res Pract [Internet]. 2014 [cited 2022 Aug 9];2014. Available from:
714. Updates to the Standards of Medical Care in Diabetes-2018. https://pubmed.ncbi.nlm.nih.gov/24711954/
Diabetes Care [Internet]. 2018 Sep 1 [cited 2022 Aug 9];41(9):2045–7. 729. Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC.
Available from: https://pubmed.ncbi.nlm.nih.gov/30135199/ Obesity, fat distribution, and weight gain as risk factors for clinical dia-
715. Bassett J, International Diabetes Institute., World Health betes in men. Diabetes Care [Internet]. 1994 [cited 2022
Organization. Regional Office for the Western Pacific., International Aug 9];17(9):961–9. Available from: https://pubmed.ncbi.nlm.nih.gov/
Association for the Study of Obesity., International Obesity TaskForce. 7988316/
The Asia-Pacific perspective : redefining obesity and its treatment. 730. Gulati S, Misra A. Sugar intake, obesity, and diabetes in India.
Australia: Health Communications Australia; 2000. 56 p. Nutrients [Internet]. 2014 Dec 22 [cited 2022 Aug 9];6(12):5955–74.
716. Ranjani H, Mehreen TS, Pradeepa R, Anjana RM, Garg R, Anand K, Available from: https://pubmed.ncbi.nlm.nih.gov/25533007/
et al. Epidemiology of childhood overweight & obesity in India: A sys- 731. Boschmann M, Michalsen A. Fasting therapy - old and new per-
tematic review. Indian J Med Res [Internet]. 2016 Feb 1 [cited 2022 spectives. Forsch Komplementmed [Internet]. 2013 Dec [cited 2022
Aug 9];143(2):160–74. Available from: https:// Aug 9];20(6):410–1. Available from: https://pubmed.ncbi.nlm.nih.gov/
pubmed.ncbi.nlm.nih.gov/27121514/ 24434754/
717. Pradeepa R, Anjana RM, Joshi SR, Bhansali A, Deepa M, Joshi PP, 732. Hassanein M, Al-Arouj M, Hamdy O, Bebakar WMW, Jabbar A,
et al. Prevalence of generalized & abdominal obesity in urban & rural Al-Madani A, et al. Diabetes and Ramadan: Practical guidelines. Diabetes
India- the ICMR - INDIAB Study (Phase-I) [ICMR - INDIAB-3]. Indian Res Clin Pract [Internet]. 2017 Apr 1 [cited 2022 Aug 9];126:303–16.
J Med Res [Internet]. 2015 Aug 1 [cited 2022 Aug 9];142(2):139. Available from: https://pubmed.ncbi.nlm.nih.gov/28347497/
Available from: /pmc/articles/PMC4613435/ 733. Consensus statement for diagnosis of obesity, abdominal obesity and
718. Misra A, Khurana L. Obesity and the metabolic syndrome in devel- the metabolic syndrome for Asian Indians and recommendations for
oping countries. J Clin Endocrinol Metab [Internet]. 2008 [cited 2022 physical activity, medical and surgical management - PubMed
[ I n t e r n e t] . [ c i t ed 2 0 2 2 A u g 9 ] . A v ai l a b l e f r o m : h t t p s : / / [Internet]. 2006 [cited 2022 Aug 9];14(6):1085–92. Available from:

pubmed.ncbi.nlm.nih.gov/19582986/ https://onlinelibrary.wiley.com/doi/abs/10.1038/oby.2006.124
734. Anoop S, Misra A, Bhatt SP, Gulati S, Mahajan H. High fasting C- 749. Misra A, Sharma R, Gulati S, Joshi SR, Sharma V, Ghafoorunissa,
peptide levels and insulin resistance in non-lean & non-obese (BMI >19 et al. Consensus Dietary Guidelines for Healthy Living and Prevention of
to 2) Asian Indians with type 2 diabetes are independently associated with Obesity, the Metabolic Syndrome, Diabetes, and Related Disorders in
high intra-abdominal fat and liver span. Diabetes Metab Syndr [Internet]. Asian Indians. https://home.liebertpub.com/dia [Internet]. 2011 May 25
2019 Jan 1 [cited 2022 Aug 8];13(1):708–15. Available from: https:// [cited 2022 Aug 9];13(6):683–94. Available from: https://
pubmed.ncbi.nlm.nih.gov/30641793/ www.liebertpub.com/doi/10.1089/dia.2010.0198
735. Misra A, Vikram NK. Clinical and pathophysiological consequences 750. Gulati S, Misra A, Tiwari R, Sharma M, Pandey RM, Yadav CP.
of abdominal adiposity and abdominal adipose tissue depots. Nutrition Effect of high-protein meal replacement on weight and cardiometabolic
[Internet]. 2003 May 1 [cited 2022 Aug 8];19(5):457–66. Available from: profile in overweight/obese Asian Indians in North India. Br J Nutr
https://pubmed.ncbi.nlm.nih.gov/12714101/ [Internet]. 2017 Jun 14 [cited 2022 Aug 9];117(11):1531–40. Available
736. Kapoor N, Lotfaliany M, Sathish T, Thankappan KR, Thomas N, from: https://pubmed.ncbi.nlm.nih.gov/28653586/
Furler J, et al. Prevalence of normal weight obesity and its associated 751. Current Treatment Strategies for Obesity Including Indian scenario |
cardio-metabolic risk factors – Results from the baseline data of the Semantic Scholar [Internet]. [cited 2022 Aug 9]. Available from: https://
Kerala Diabetes Prevention Program (KDPP). PLoS One [Internet]. www.semanticscholar.org/paper/Current-Treatment-Strategies-for-
2020 Aug 1 [cited 2022 Aug 8];15(8). Available from: /pmc/articles/ O b e s i t y - I n c l u d i n g - P r a s h a r /
PMC7446975/ ca4d81e4f3c5d37cdadf5586f843af9229aca475
737. Kapoor N, Lotfaliany M, Sathish T, Thankappan KR, Tapp RJ, 752. Pascale RW, Wing RR, Butler BA, Mullen M, Bononi P. Effects of a
Thomas N, et al. Effect of a Peer-led Lifestyle Intervention on behavioral weight loss program stressing calorie restriction versus calorie
Individuals With Normal Weight Obesity: Insights From the Kerala plus fat restriction in obese individuals with NIDDM or a family history
Diabetes Prevention Program. Clin Ther. 2020;42(8):1618–24. o f d i a b e t es . D i a b e t e s C a r e [ I n t e r n e t ] . 1 9 9 5 [ c i t e d 2 0 2 2
738. Jayawardena R, Jeyakumar DT, Misra A, Hills AP, Ranasinghe P. Aug 9];18(9):1241–8. Available from: https://pubmed.ncbi.nlm.nih.gov/
Obesity: A potential risk factor for infection and mortality in the current 8612437/
COVID-19 epidemic. Diabetes Metab Syndr. 14(6):2199–203. 753. Systematic review of the long-term effects and economic conse-
739. Kaur M, Aggarwal R, Ganesh V, Kumar R, Patel N, Ayub A, et al. quences of treatments for obesity and implications for health improve-
Clinical Course and Outcome of Critically Ill Obese Patients with ment - NIHR Health Technology Assessment programme: Executive
COVID-19 Admitted in Intensive Care Unit of a Single Center: Our Summaries - NCBI Bookshelf [Internet]. [cited 2022 Aug 9]. Available
Experience and Review. Indian J Crit Care Med. 2021 from: https://www.ncbi.nlm.nih.gov/books/NBK62231/
Dec;25(12):1382–6. 754. Brown T, Smith S, Bhopal R, Kasim A, Summerbell C. Diet and
740. Pal R, Aggarwal A, Singh T, Sharma S, Khandelwal N, Garg A, physical activity interventions to prevent or treat obesity in South Asian
et al. Diagnostic cut-offs, prevalence, and biochemical predictors of sar- children and adults: a systematic review and meta-analysis. Int J Environ
copenia in healthy Indian adults: The Sarcopenia-Chandigarh Urban Res Public Health [Internet]. 2015 Jan 9 [cited 2022 Aug 9];12(1):566–
Bone Epidemiological Study (Sarco-CUBES). Eur Geriatr Med. 94. Available from: https://pubmed.ncbi.nlm.nih.gov/25584423/
2020;11(5):725–36. 755. Swift DL, Johannsen NM, Lavie CJ, Earnest CP, Church TS. The
741. Gallagher EJ, LeRoith D. Obesity and Diabetes: The Increased Risk role of exercise and physical activity in weight loss and maintenance.
of Cancer and Cancer-Related Mortality. Physiol Rev [Internet]. 2015 Prog Cardiovasc Dis [Internet]. 2014 Jan [cited 2022
Jul 1 [cited 2022 Aug 9];95(3):727. Available from: /pmc/articles/ Aug 9];56(4):441–7. Available from: https://pubmed.ncbi.nlm.nih.gov/
PMC4491542/ 24438736/
742. Belfiore A, Frasca F, Pandini G, … LSE, 2009 undefined. Insulin 756. Williamson DF, Madans J, Anda RF, Kleinman JC, Kahn HS, Byers
receptor isoforms and insulin receptor/insulin-like growth factor receptor T. Recreational physical activity and ten-year weight change in a US
hybrids in physiology and disease. academic.oup.com [Internet]. [cited national cohort. Int J Obes Relat Metab Disord [Internet]. 1993 May 1
2022 Aug 9]; Available from: https://academic.oup.com/edrv/article-ab- [cited 2022 Aug 9];17(5):279–86. Available from: https://
stract/30/6/586/2355072 europepmc.org/article/med/8389337
743. de Beer JC, Liebenberg L. Does cancer risk increase with HbA1c, 757. Littman AJ, Kristal AR, White E. Effects of physical activity inten-
independent of diabetes? Br J Cancer [Internet]. 2014 Apr 4 [cited 2022 sity, frequency, and activity type on 10-y weight change in middle-aged
Aug 9];110(9):2361. Available from: /pmc/articles/PMC4007234/ men and women. Int J Obes (Lond) [Internet]. 2005 May [cited 2022
744. Melvin J, Holmberg L, Rohrmann S, … MLJ of cancer, 2013 un- Aug 9];29(5):524–33. Available from: https://pubmed.ncbi.nlm.nih.gov/
defined. Serum lipid profiles and cancer risk in the context of obesity: 15672107/
four meta-analyses. hindawi.com [Internet]. [cited 2022 Aug 9]; 758. Ballor D, Smith D, … LTI journal of, 1990 undefined. Neither high-
Available from: https://www.hindawi.com/journals/jce/2013/823849/ nor low-intensity exercise promotes whole-body conservation of protein
745. Behl S, Misra A. Management of obesity in adult Asian Indians. during severe dietary restrictions. europepmc.org [Internet]. [cited 2022
Indian Heart J. 2017 Jul;69(4):539–44. Aug 9]; Available from: https://europepmc.org/article/med/2341232
746. Fujimoto WY, Jablonski KA, Bray GA, Kriska A, Barrett-Connor E, 759. Melanson EL, MacLean PS, Hill JO. Exercise improves fat metab-
Haffner S, et al. Body Size and Shape Changes and the Risk of Diabetes olism in muscle but does not increase 24-h fat oxidation. Exerc Sport Sci
in the Diabetes Prevention Program. Diabetes [Internet]. 2007 Jun [cited Rev [Internet]. 2009 [cited 2022 Aug 9];37(2):93–101. Available from:
2022 Aug 9];56(6):1680. Available from: /pmc/articles/PMC2528279/ https://pubmed.ncbi.nlm.nih.gov/19305201/
747. Wing RR, Bahnson JL, Bray GA, Clark JM, Coday M, Egan C, et al. 760. Church TS, Blair SN, Cocreham S, Johannsen N, Johnson W,
Long Term Effects of a Lifestyle Intervention on Weight and Kramer K, et al. Effects of aerobic and resistance training on hemoglobin
Cardiovascular Risk Factors in Individuals with Type 2 Diabetes: Four A1c levels in patients with type 2 diabetes: a randomized controlled trial.
Year Results of the Look AHEAD Trial. Arch Intern Med [Internet]. JAMA [Internet]. 2010 Nov 24 [cited 2022 Aug 9];304(20):2253–62.
2010 Sep 9 [cited 2022 Aug 9];170(17):1566. Available from: /pmc/ Available from: https://pubmed.ncbi.nlm.nih.gov/21098771/
articles/PMC3084497/ 761. Global Strategy on Diet, Physical Activity and Health - 2004
748. Gurka MJ, Wolf AM, Conaway MR, Crowther JQ, Nadler JL, [Internet]. [cited 2022 Aug 9]. Available from: https://www.who.int/pub-
Bovbjerg VE. Lifestyle intervention in obese patients with type 2 diabe- lications/i/item/9241592222
tes: impact of the patient’s educational background. Wiley Online Library
762. Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, Inhibitors, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists, and
McCombie L, et al. Primary care-led weight management for remission Orlistat based Multidrug Therapy in Glycemic Control, Weight Loss,
of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The and Euglycemia in Diabesity: A Real-World Experience. Indian J
Lancet [Internet]. 2018 Feb 10 [cited 2022 Aug 9];391(10120):541–51. Endocrinol Metab [Internet]. 2019 Jul 1 [cited 2022 Aug 8];23(4):460–
Available from: http://www.thelancet.com/article/S0140673617331021/ 7. Available from: https://pubmed.ncbi.nlm.nih.gov/31741907/
fulltext 774. Bays HE, Weinstein R, Law G, Canovatchel W. Canagliflozin:
763. Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, effects in overweight and obese subjects without diabetes mellitus.
McCombie L, et al. Durability of a primary care-led weight-management Obesity (Silver Spring) [Internet]. 2014 [cited 2022 Aug 8];22(4):1042–
intervention for remission of type 2 diabetes: 2-year results of the 9. Available from: https://pubmed.ncbi.nlm.nih.gov/24227660/
DiRECT open-label, cluster-randomised trial. Lancet Diabetes 775. Zheng H, Liu M, Li S, Shi Q, Zhang S, Zhou Y, et al. Sodium-
Endocrinol [Internet]. 2019 May 1 [cited 2022 Aug 9];7(5):344–55. Glucose Co-Transporter-2 Inhibitors in Non-Diabetic Adults With
Available from: https://pubmed.ncbi.nlm.nih.gov/30852132/ Overweight or Obesity: A Systematic Review and Meta-Analysis. Front
764. Fogelholm M, Larsen TM, Westerterp-Planten M, Macdonald I, Endocrinol (Lausanne). 2021 Aug 16;12.
Alfredo Martinez J, Boyadjieva N, et al. PREVIEW: Prevention of 776. Ghosh A, Dutta K, Bhatt SP, Gupta R, Tyagi K, Ansari IA, et al.
Diabetes through Lifestyle Intervention and Population Studies in Dapagliflozin Improves Body Fat Patterning, and Hepatic and Pancreatic
Europe and around the World. Design, Methods, and Baseline Fat in Patients With Type 2 Diabetes in North India. J Clin Endocrinol
Participant Description of an Adult Cohort Enrolled into a Three-Year Metab. 2022;107(6):e2267–75.
Randomised Clinical Trial. Nutrients [Internet]. 2017 Jun 20 [cited 2022 777. Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists
Aug 9];9(6). Available from: https://pubmed.ncbi.nlm.nih.gov/ in the treatment of type 2 diabetes – state-of-the-art. Mol Metab. 2021
28632180/ Apr;46:101102.
765. Swindell N, Mackintosh K, Mcnarry M, Stephens JW, Sluik D, 778. Tamborlane W v., Barrientos-Pérez M, Fainberg U, Frimer-Larsen
Fogelholm M, et al. Objectively Measured Physical Activity and H, Hafez M, Hale PM, et al. Liraglutide in Children and Adolescents with
Sedentary Time Are Associated With Cardiometabolic Risk Factors in Type 2 Diabetes. N Engl J Med [Internet]. 2019 Aug 15 [cited 2022
Adults With Prediabetes: The PREVIEW Study. Diabetes Care [Internet]. Aug 8];381(7):637–46. Available from: https://
2018 Mar 1 [cited 2022 Aug 9];41(3):562–9. Available from: https:// pubmed.ncbi.nlm.nih.gov/31034184/
pubmed.ncbi.nlm.nih.gov/29158249/ 779. Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, et al.
766. Christensen P, Meinert Larsen T, Westerterp-Plantenga M, Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor
Macdonald I, Martinez JA, Handjiev S, et al. Men and women respond agonist, in patients with type 2 diabetes: a randomised, placebo-
differently to rapid weight loss: Metabolic outcomes of a multi‐centre controlled and active comparator-controlled phase 2 trial. Lancet
intervention study after a low‐energy diet in 2500 overweight, individuals [Internet]. 2018 Nov 17 [cited 2022 Aug 8];392(10160):2180–93.
with pre‐diabetes (PREVIEW). Diabetes Obes Metab [Internet]. 2018 Available from: https://pubmed.ncbi.nlm.nih.gov/30293770/
Dec 1 [cited 2022 Aug 9];20(12):2840. Available from: /pmc/articles/ 780. Karagiannis T, Avgerinos I, Liakos A, del Prato S, Matthews DR,
PMC6282840/ Tsapas A, et al. Management of type 2 diabetes with the dual GIP/GLP-1
767. Hendricks EJ. Off-label drugs for weight management. Diabetes receptor agonist tirzepatide: a systematic review and meta-analysis.
Metab Syndr Obes [Internet]. 2017 Jun 10 [cited 2022 Aug 9];10:223. Diabetologia [Internet]. 2022 Aug 17 [cited 2022 Aug 8];65(8).
Available from: /pmc/articles/PMC5473499/ Available from: https://pubmed.ncbi.nlm.nih.gov/35579691/
768. Lee A, Morley JE. Metformin decreases food consumption and 781. Kashyap SR, Bhatt DL, Wolski K, Watanabe RM, Abdul-Ghani M,
induces weight loss in subjects with obesity with type II non-insulin- Abood B, et al. Metabolic effects of bariatric surgery in patients with
dependent diabetes. Obes Res [Internet]. 1998 [cited 2022 moderate obesity and type 2 diabetes: analysis of a randomized control
Aug 9];6(1):47–53. Available from: https://pubmed.ncbi.nlm.nih.gov/ trial comparing surgery with intensive medical treatment. Diabetes Care
9526970/ [Internet]. 2013 [cited 2022 Aug 9];36(8):2175–82. Available from:
769. Aldekhail NM, Logue J, Mcloone P, Morrison DS. Effect of orlistat https://pubmed.ncbi.nlm.nih.gov/23439632/
on glycaemic control in overweight and obese patients with type 2 dia- 782. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer
betes mellitus: a systematic review and meta-analysis of randomized con- SA, et al. Bariatric Surgery versus Intensive Medical Therapy for
trolled trials. Obesity Reviews [Internet]. 2015 Dec 1 [cited 2022 Diabetes - 5-Year Outcomes. N Engl J Med [Internet]. 2017 Feb 16 [cited
Aug 9];16(12):1071–80. Available from: https:// 2022 Aug 9];376(7):641–51. Available from: https://
onlinelibrary.wiley.com/doi/full/10.1111/obr.12318 pubmed.ncbi.nlm.nih.gov/28199805/
770. Nauck MA, Meier JJ. MANAGEMENT OF ENDOCRINE 783. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer
DISEASE: Are all GLP-1 agonists equal in the treatment of type 2 dia- SA, et al. Bariatric Surgery versus Intensive Medical Therapy for
betes? Eur J Endocrinol [Internet]. 2019 Dec 1 [cited 2022 Diabetes - 5-Year Outcomes. N Engl J Med [Internet]. 2017 Feb 16 [cited
Aug 8];181(6):R211–34. Available from: https://eje.bioscientifica.com/ 2022 Aug 9];376(7):641–51. Available from: https://
view/journals/eje/181/6/EJE-19-0566.xml pubmed.ncbi.nlm.nih.gov/28199805/
771. Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, 784. Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP,
et al. Effects of once-weekly semaglutide on appetite, energy intake, Pothier CE, et al. Bariatric Surgery versus Intensive Medical Therapy in
control of eating, food preference and body weight in subjects with obe- Obese Patients with Diabetes. N Engl J Med [Internet]. 2012 Apr 4 [cited
sity. Diabetes Obes Metab [Internet]. 2017 Sep 1 [cited 2022 2022 Aug 9];366(17):1567. Available from: /pmc/articles/PMC3372918/
Aug 8];19(9):1242–51. Available from: https:// 785. Yan Y, Sha Y, Yao G, Wang S, Kong F, Liu H, et al. Roux-en-Y
pubmed.ncbi.nlm.nih.gov/28266779/ Gastric Bypass Versus Medical Treatment for Type 2 Diabetes Mellitus
772. Bolinder J, Ljunggren O, Johansson L, Wilding J, Langkilde AM, in Obese Patients: A Systematic Review and Meta-Analysis of
Sjöström CD, et al. Dapagliflozin maintains glycaemic control while Randomized Controlled Trials. Medicine [Internet]. 2016 Apr 1 [cited
reducing weight and body fat mass over 2 years in patients with type 2 2022 Aug 9];95(17). Available from: /pmc/articles/PMC4998704/
diabetes mellitus inadequately controlled on metformin. Diabetes Obes 786. Bhasker AG, Remedios C, Batra P, Sood A, Shaikh S, Lakdawala
Metab [Internet]. 2014 [cited 2022 Aug 8];16(2):159–69. Available from: M. Predictors of Remission of T2DM and Metabolic Effects after
https://pubmed.ncbi.nlm.nih.gov/23906445/ Laparoscopic Roux-en-y Gastric Bypass in Obese Indian Diabetics-a 5-
773. Dutta D, Jaisani R, Khandelwal D, Ghosh S, Malhotra R, Kalra S. Year Study. Obes Surg [Internet]. 2015 Nov 16 [cited 2022
Role of Metformin, Sodium-Glucose Cotransporter-2 (SGLT2)
Aug 9];25(7):1191–7. Available from: https://pubmed.ncbi.nlm.nih.gov/ Aug 11];28(1):19–24. Available from: https://pubmed.ncbi.nlm.nih.gov/
25399348/ 29467562/
787. Dasgupta A, Wasir J, Beloyartseva M, Malhotra S, Mithal A. An 799. Kumar PR, Bhansali A, Ravikiran M, Bhansali S, Dutta P, Thakur
observational longitudinal study of the impact of sleeve gastrectomy on JS, et al. Utility of glycated hemoglobin in diagnosing type 2 diabetes
glycemic control in type 2 diabetes mellitus. Diabetes Technol Ther mellitus: a community-based study. J Clin Endocrinol Metab [Internet].
[Internet]. 2013 Dec 1 [cited 2022 Aug 9];15(12):990–5. Available from: 2010 [cited 2022 Aug 11];95(6):2832–5. Available from: https://
788. Lakdawala M, Shaikh S, Bandukwala S, Remedios C, Diet M, Shah 800. Mohan V, Vijayachandrika V, Gokulakrishnan K, Anjana RM,
M, et al. Roux-en-Y gastric bypass stands the test of time: 5-year results in Ganesan A, Weber MB, et al. A1C cut points to define various glucose
low body mass index (30–35 kg/m2) Indian patients with type 2 diabetes intolerance groups in Asian Indians. Diabetes Care [Internet]. 2010 Mar
mellitus. Elsevier [Internet]. 2013 [cited 2022 Aug 9];9:370–8. Available [cited 2022 Aug 11];33(3):515–9. Available from: https://
from: https://www.sciencedirect.com/science/article/pii/ pubmed.ncbi.nlm.nih.gov/19903752/
S155072891200278X 801. Herman WH, Ye W, Griffin SJ, Simmons RK, Davies MJ, Khunti
789. Weight-Loss and Weight-Management Devices | FDA [Internet]. K, et al. Early Detection and Treatment of Type 2 Diabetes Reduce
[cited 2022 Aug 9]. Available from: https://www.fda.gov/medical-de- Cardiovascular Morbidity and Mortality: A Simulation of the Results of
vices/products-and-medical-procedures/weight-loss-and-weight-manage- the Anglo-Danish-Dutch Study of Intensive Treatment in People With
ment-devices Screen-Detected Diabetes in Primary Care (ADDITION-Europe).
790. Association AD. 2. Classification and Diagnosis of Diabetes: Diabetes Care [Internet]. 2015 Aug 1 [cited 2022 Aug 11];38(8):1449–
Standards of Medical Care in Diabetes—2019. Diabetes Care [Internet]. 55. Available from: https://pubmed.ncbi.nlm.nih.gov/25986661/
2019 Jan 1 [cited 2022 Aug 11];42(Supplement_1):S13–28. Available 802. Unnikrishnan R, Mohan V. Why screening for type 2 diabetes is
from: https://diabetesjournals.org/care/article/42/Supplement_1/S13/ necessary even in poor resource settings. J Diabetes Complications
31150/2-Classification-and-Diagnosis-of-Diabetes [Internet]. 2015 Sep 1 [cited 2022 Aug 11];29(7):961–4. Available from:
791. Nguyen KA, Peer N, de Villiers A, Mukasa B, Matsha TE, Mills EJ, https://pubmed.ncbi.nlm.nih.gov/26099834/
et al. Glycated haemoglobin threshold for dysglycaemia screening, and 803. Einarson TR, Bereza BG, Acs A, Jensen R. Systematic literature
application to metabolic syndrome diagnosis in HIV-infected Africans. review of the health economic implications of early detection by screen-
PLoS One [Internet]. 2019 Jan 1 [cited 2022 Aug 11];14(1):e0211483. ing populations at risk for type 2 diabetes. Curr Med Res Opin [Internet].
Available from: https://journals.plos.org/plosone/article?id=10.1371/ 2017 Feb 1 [cited 2022 Aug 11];33(2):331–58. Available from: https://
journal.pone.0211483 pubmed.ncbi.nlm.nih.gov/27819150/
792. Nathan DM, Balkau B, Bonora E, Borch-Johnsen K, Buse JB, 804. Madhu S v., Sandeep G, Mishra BK, Aslam M. High prevalence of
Colagiuri S, et al. International Expert Committee Report on the Role diabetes, prediabetes and obesity among residents of East Delhi - The
of the A1C Assay in the Diagnosis of Diabetes. Diabetes Care Delhi urban diabetes survey (DUDS). Diabetes Metab Syndr [Internet].
[Internet]. 2009 Jul [cited 2022 Aug 11];32(7):1327. Available from: 2018 Nov 1 [cited 2022 Aug 11];12(6):923–7. Available from: https://
/pmc/articles/PMC2699715/ pubmed.ncbi.nlm.nih.gov/29803508/
793. Hasslacher C, Kulozik F, Platten I, Lorenzo Bermejo J. Glycated 805. Venugopal V, Selvaraj K, Majumdar A, Chinnakali P, Roy G.
albumin and HbA1c as predictors of mortality and vascular complications Opportunistic screening for diabetes mellitus among adults attending a
in type 2 diabetes patients with normal and moderately impaired renal primary health center in Puducherry. Int J Med Sci Public Health.
function: 5-year results from a 380 patient cohort. J Diabetes Res Clin 2015;4(9):1206.
Metab [Internet]. 2014 Oct 30 [cited 2022 Aug 11];3(1):9. Available 806. Ramachandran A, Snehalatha C, Vijay V, Wareham NJ, Colagiuri S.
from: http://www.hoajonline.com/jdrcm/2050-0866/3/9 Derivation and validation of diabetes risk score for urban Asian Indians.
794. Lauritzen T, Sandbaek A, Skriver M v., Borch-Johnsen K. HbA1c Diabetes Res Clin Pract [Internet]. 2005 Oct [cited 2022
and cardiovascular risk score identify people who may benefit from pre- Aug 11];70(1):63–70. Available from: https://pubmed.ncbi.nlm.nih.gov/
ventive interventions: a 7 year follow-up of a high-risk screening pro- 16126124/
gramme for diabetes in primary care (ADDITION), Denmark. 807. v Mohan, R Deepa, M Deepa, S Somannavar, M Datta. A simplified
Diabetologia [Internet]. 2011 Jun [cited 2022 Aug 11];54(6):1318–26. Indian Diabetes Risk Score for screening for undiagnosed diabetic sub-
Available from: https://pubmed.ncbi.nlm.nih.gov/21340624/ jects. J Assoc Physicians India . 2005;53(Sep):759–63.
795. Lim WY, Ma S, Heng D, Tai ES, Khoo CM, Loh TP. Screening for 808. Mohan V, Vassy JL, Pradeepa R, Deepa M, Subashini S. The Indian
diabetes with HbA1c: Test performance of HbA1c compared to fasting type 2 diabetes risk score also helps identify those at risk of macrovascu-
plasma glucose among Chinese, Malay and Indian community residents lar disease and neuropathy (CURES-77). J Assoc Physicians India.
in Singapore. Sci Rep [Internet]. 2018 Dec 1 [cited 2022 Aug 11];8(1). 2010;58:430–3.
Available from: https://pubmed.ncbi.nlm.nih.gov/30127499/ 809. Bowen ME, Xuan L, Lingvay I, Halm EA. Random blood glucose: a
796. Guo F, Moellering DR, Garvey WT. Use of HbA1c for diagnoses of robust risk factor for type 2 diabetes. J Clin Endocrinol Metab [Internet].
diabetes and prediabetes: comparison with diagnoses based on fasting 2015 Apr 1 [cited 2022 Aug 11];100(4):1503–10. Available from: https://
and 2-hr glucose values and effects of gender, race, and age. Metab pubmed.ncbi.nlm.nih.gov/25650899/
Syndr Relat Disord [Internet]. 2014 Jun 1 [cited 2022 810. Bowen ME, Xuan L, Lingvay I, Halm EA. Performance of a
Aug 11];12(5):258–68. Available from: https:// Random Glucose Case-Finding Strategy to Detect Undiagnosed
pubmed.ncbi.nlm.nih.gov/24512556/ Diabetes. Am J Prev Med [Internet]. 2017 Jun 1 [cited 2022
797. Radhakrishna P, Vinod KV, Sujiv A, Swaminathan RP. Comparison Aug 11];52(6):710–6. Available from: https://pubmed.ncbi.nlm.nih.gov/
of Hemoglobin A1c with Fasting and 2-h Plasma Glucose Tests for 28279547/
Diagnosis of Diabetes and Prediabetes among High-risk South Indians. 811. Somannavar S, Ganesan A, Deepa M, Datta M, Mohan V. Random
Indian J Endocrinol Metab [Internet]. 2018 Jan 1 [cited 2022 capillary blood glucose cut points for diabetes and pre-diabetes derived
Aug 11];22(1):50. Available from: /pmc/articles/PMC5838911/ from community-based opportunistic screening in India. Diabetes Care
798. Prakaschandra R, Prakesh Naidoo D. Fasting Plasma Glucose and [Internet]. 2009 Apr [cited 2022 Aug 11];32(4):641–3. Available from:
the HbA1c Are Not Optimal Screening Modalities for the Diagnosis of https://pubmed.ncbi.nlm.nih.gov/19073758/
New Diabetes in Previously Undiagnosed Asian Indian Community 812. Elman K, Wainstein J, Boaz M, Jakubowicz D, Bar-Dayan Y.
Participants. Ethn Dis [Internet]. 2018 Dec 1 [cited 2022 Random blood glucose screening at a public health station encouraged
high risk subjects to make lifestyle changes. Int J Clin Pract [Internet].
2017 Aug 1 [cited 2022 Aug 11];71(8). Available from: https:// [cited 2022 Aug 11];54(12):3022–7. Available from: https://
813. Barry E, Roberts S, Oke J, Vijayaraghavan S, Normansell R, 826. Winkley K, Kristensen C, Fosbury J. Sexual health and function in
Greenhalgh T. Efficacy and effectiveness of screen and treat policies in women with diabetes. Diabetic Medicine [Internet]. 2021 Nov 1 [cited
prevention of type 2 diabetes: systematic review and meta-analysis of 2022 Sep 15];38(11):e14644. Available from: https://
screening tests and interventions. BMJ [Internet]. 2017 Jan 4 [cited onlinelibrary.wiley.com/doi/full/10.1111/dme.14644
2022 Aug 11];356. Available from: https://www.bmj.com/content/356/ 827. Maiorino MI, Bellastella G, Esposito K. Diabetes and sexual dys-
bmj.i6538 function: current perspectives. Diabetes Metab Syndr Obes [Internet].
814. Gupta Y, Kapoor D, Desai A, Praveen D, Joshi R, Rozati R, et al. 2014 Mar 6 [cited 2022 Aug 12];7:95–105. Available from: https://
Conversion of gestational diabetes mellitus to future Type 2 diabetes pubmed.ncbi.nlm.nih.gov/24623985/
mellitus and the predictive value of HbA 1c in an Indian cohort. Diabet 828. Enzlin P, Rosen R, Wiegel M, Brown J, Wessells H, Gatcomb P,
Med [Internet]. 2017 Jan 1 [cited 2022 Aug 11];34(1):37–43. Available et al. Sexual dysfunction in women with type 1 diabetes: long-term find-
from: https://pubmed.ncbi.nlm.nih.gov/26926329/ ings from the DCCT/ EDIC study cohort. Diabetes Care [Internet]. 2009
815. Bertran EA, Berlie HD, Taylor A, Divine G, Jaber LA. Diagnostic May [cited 2022 Aug 12];32(5):780–5. Available from: https://
performance of HbA 1c for diabetes in Arab vs. European populations: a pubmed.ncbi.nlm.nih.gov/19407075/
systematic review and meta-analysis. Diabet Med [Internet]. 2017 Feb 1 829. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay
[cited 2022 Aug 11];34(2):156–66. Available from: https:// JB. Impotence and its medical and psychosocial correlates: results of the
pubmed.ncbi.nlm.nih.gov/26996656/ Massachusetts Male Aging Study. J Urol [Internet]. 1994 [cited 2022
816. Cavagnolli G, Pimentel AL, Freitas PAC, Gross JL, Camargo JL. Aug 12];151(1):54–61. Available from: https://
Effect of ethnicity on HbA1c levels in individuals without diabetes: pubmed.ncbi.nlm.nih.gov/8254833/
Systematic review and meta-analysis. PLoS One [Internet]. 2017 Feb 1 830. Kouidrat Y, Pizzol D, Cosco T, Thompson T, Carnaghi M, Bertoldo
[cited 2022 Aug 11];12(2):e0171315. Available from: https:// A, et al. High prevalence of erectile dysfunction in diabetes: a systematic
journals.plos.org/plosone/article?id=10.1371/journal.pone.0171315 review and meta-analysis of 145 studies. Diabet Med [Internet]. 2017 Sep
817. Hellgren M, Hjörleifsdottir Steiner K, Bennet L. Haemoglobin A1c 1 [cited 2022 Aug 12];34(9):1185–92. Available from: https://
as a screening tool for type 2 diabetes and prediabetes in populations of pubmed.ncbi.nlm.nih.gov/28722225/
Swedish and Middle-East ancestry. Prim Care Diabetes [Internet]. 2017 831. Sondhi M, Kakar A, Gogia A. Prevalence of erectile dysfunction in
Aug 1 [cited 2022 Aug 11];11(4):337–43. Available from: https:// diabetic patients. Curr Med Res Pract . 2018;88–91.
pubmed.ncbi.nlm.nih.gov/28545842/ 832. Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP,
818. Madhu S v., Raj A, Gupta S, Giri S, Rusia U. Effect of iron defi- McKinlay JB. Incidence of erectile dysfunction in men 40 to 69 years old:
ciency anemia and iron supplementation on HbA1c levels - Implications longitudinal results from the Massachusetts male aging study. J Urol.
for diagnosis of prediabetes and diabetes mellitus in Asian Indians. Clin 2000 Feb;163(2):460–3.
Chim Acta [Internet]. 2017 May 1 [cited 2022 Aug 11];468:225–9. 833. Angulo J, Cuevas P, Fernández A, Gabancho S, Allona A, Martín-
Available from: https://pubmed.ncbi.nlm.nih.gov/27717800/ Morales A, et al. Diabetes impairs endothelium-dependent relaxation of
819. Unnikrishnan R, Anjana RM, Deepa M, Pradeepa R, Joshi SR, human penile vascular tissues mediated by NO and EDHF. Biochem
Bhansali A, et al. Glycemic control among individuals with self- Biophys Res Commun [Internet]. 2003 Dec 26 [cited 2022
reported diabetes in India–the ICMR-INDIAB Study. Diabetes Technol Aug 12];312(4):1202–8. Available from: https://
Ther [Internet]. 2014 Sep 1 [cited 2022 Aug 11];16(9):596–603. pubmed.ncbi.nlm.nih.gov/14652001/
Available from: https://pubmed.ncbi.nlm.nih.gov/25101698/ 834. Kapoor D, Clarke S, Channer KS, Jones TH. Erectile dysfunction is
820. Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes associated with low bioactive testosterone levels and visceral adiposity in
mellitus after gestational diabetes: a systematic review and meta-analysis. men with type 2 diabetes. Int J Androl [Internet]. 2007 Dec [cited 2022
Lancet [Internet]. 2009 [cited 2022 Aug 11];373(9677):1773–9. Aug 12];30(6):500–7. Available from: https://pubmed.ncbi.nlm.nih.gov/
Available from: https://pubmed.ncbi.nlm.nih.gov/19465232/ 18028199/
821. Retnakaran R. Glucose tolerance status in pregnancy: a window to 835. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2019.
the future risk of diabetes and cardiovascular disease in young women. Diabetes Care [Internet]. 2019 Jan 1 [cited 2022 Aug 12];42(Suppl
Curr Diabetes Rev [Internet]. 2009 Nov 4 [cited 2022 Aug 11];5(4):239– 1):S61–70. Available from: https://pubmed.ncbi.nlm.nih.gov/30559232/
44. Available from: https://pubmed.ncbi.nlm.nih.gov/19604132/ 836. Bajaj S, Jawad F, Islam N, Mahtab H, Bhattarai J, Shrestha D, et al.
822. Damm P. Future risk of diabetes in mother and child after gestational South Asian women with diabetes: Psychosocial challenges and manage-
diabetes mellitus. Int J Gynaecol Obstet [Internet]. 2009 [cited 2022 ment: Consensus statement. Indian J Endocrinol Metab [Internet]. 2013
A ug 1 1] ; 10 4 S u p p l 1 ( S U P P L . ) . Av a i l a b l e f r o m : h t t p s : / / [cite d 2022 Aug 12];17(4):548. Available from: https://
823. Madhu S v. Diabetes in pregnancy—a critical window of opportu- 837. Pontiroli AE, Cortelazzi D, Morabito A. Female sexual dysfunction
nity. International Journal of Diabetes in Developing Countries 2018 38:1 and diabetes: A systematic review and meta-analysis. J Sex Med .
[Internet]. 2018 Feb 10 [cited 2022 Aug 11];38(1):1–3. Available from: 2013;1044–51.
https://link.springer.com/article/10.1007/s13410-018-0614-5 838. Basson R, Berman J, Burnett A, Derogatis L, Ferguson D, Fourcroy
824. Wabitsch M, Hauner H, Hertrampf M, Muche R, Hay B, Mayer H, J, et al. Report of the international consensus development conference on
et al. Type II diabetes mellitus and impaired glucose regulation in female sexual dysfunction: definitions and classifications. J Urol. 2000
Caucasian children and adolescents with obesity living in Germany. Int Mar;163(3):888–93.
J Obes Relat Metab Disord [Intern et]. 200 4 [cited 2022 839. Kalra B, Kalra S, Chawla K, Batra P, Chhabra B. Sexual Attitudes,
Aug 11];28(2):307–13. Available from: https:// Knowledge And Function Of Women With Diabetes. The Internet
pubmed.ncbi.nlm.nih.gov/14724655/ Journal of Geriatrics and Gerontology. 2009 Dec 31;5(2).
825. Anjana RM, Pradeepa R, Deepa M, Datta M, Sudha V, 840. Seftel AD, Sun P, Swindle R. The prevalence of hypertension, hy-
Unnikrishnan R, et al. Prevalence of diabetes and prediabetes (impaired perlipidemia, diabetes mellitus and depression in men with erectile dys-
fasting glucose and/or impaired glucose tolerance) in urban and rural function. Journal of Urology [Internet]. 2004 [cited 2022 Aug 12];171(6
India: phase I results of the Indian Council of Medical Research-INdia I):2341–5. Available from: https://pubmed.ncbi.nlm.nih.gov/15126817/
DIABetes (ICMR-INDIAB) study. Diabetologia [Internet]. 2011 Dec 841. Rosen RC. Sexual dysfunction as an obstacle to compliance with
antihypertensive therapy. Blood Press Suppl. 1997;1:47–51.
842. Yamada T, Hara K, Umematsu H, Suzuki R, Kadowaki T. Erectile Mellitus. Int J Environ Res Public Health [Internet]. 2017 Sep 16 [cited
dysfunction and cardiovascular events in diabetic men: a meta-analysis of 2022 Aug 26];14(9). Available from: /pmc/articles/PMC5615610/
observational studies. PLoS One [Internet]. 2012 Sep 4 [cited 2022 857. van Cauwenberghe J, Enzlin P, Nefs G, Ruige J, Hendrieckx C, de
Aug 12];7(9). Available from: https://pubmed.ncbi.nlm.nih.gov/ Block C, et al. Prevalence of and risk factors for sexual dysfunctions in
22962586/ adults with type 1 or type 2 diabetes: Results from Diabetes MILES -
843. Meena BL, Kochar DK, Agarwal T das, Choudhary R, Kochar A. Flanders. Diabetic Medicine [Internet]. 2022 Jan 1 [cited 2022
Association between erectile dysfunction and cardiovascular risk in indi- Aug 12];39(1):e14676. Available from: https://onlinelibrary.wiley.com/
viduals with type-2 diabetes without overt cardiovascular disease. Int J doi/full/10.1111/dme.14676
Diabetes Dev Ctries [Internet]. 2009 [cited 2022 Aug 12];29(4):150. 858. LeRoith D, Smith DO. Monitoring glycemic control: the cornerstone
Available from: /pmc/articles/PMC2839128/ of diabetes care. Clin Ther [Internet]. 2005 [cited 2022
844. Alexopoulou O, Jamart J, Maiter D, Hermans MP, de Hertogh R, de Aug 10];27(10):1489–99. Available from: https://
Nayer P, et al. Erectile dysfunction and lower androgenicity in type 1 pubmed.ncbi.nlm.nih.gov/16330287/
diabetic patients. Diabetes Metab. 2001 Jun;27(3):329–36. 859. Rao P v., Makkar BM, Kumar A, Das AK, Singh AK, Mithal A,
845. Kalinchenko SY, Kozlov GI, Gontcharov NP, Katsiya G v. Oral et al. RSSDI consensus on self-monitoring of blood glucose in types 1
testosterone undecanoate reverses erectile dysfunction associated with and 2 diabetes mellitus in India. Int J Diabetes Dev Ctries [Internet]. 2018
diabetes mellitus in patients failing on sildenafil citrate therapy alone. Sep 1 [cited 2022 Aug 10];38(3):260–79. Available from: https://
Aging Male. 2003 Jun;6(2):94–9. link.springer.com/article/10.1007/s13410-018-0677-3
846. Agarwal P, Singh P, Chowdhury S, Sharma S, Majumdar A, Shah P, 860. Pimazoni-Netto A, Rodbard D, Zanella MT. Rapid improvement of
et al. A study to evaluate the prevalence of hypogonadism in Indian males glycemic control in type 2 diabetes using weekly intensive multifactorial
with Type-2 diabetes mellitus. Indian J Endocrinol Metab [Internet]. 2017 interventions: structured glucose monitoring, patient education, and ad-
Jan 1 [cited 2022 Aug 12];21(1):64. Available from: /pmc/articles/ justment of therapy-a randomized controlled trial. Diabetes Technol Ther
PMC5240083/ [Internet]. 2011 Oct 1 [cited 2022 Aug 10];13(10):997–1004. Available
847. Wing RR, Rosen RC, Fava JL, Bahnson J, Brancati F, Gendrano from: https://pubmed.ncbi.nlm.nih.gov/21751888/
INC, et al. Effects of weight loss intervention on erectile function in older 861. Rahaghi FN, Gough DA. Blood glucose dynamics. Diabetes
men with type 2 diabetes in the Look AHEAD trial. J Sex Med [Internet]. Technol Ther [Internet]. 2008 Apr 1 [cited 2022 Aug 10];10(2):81–94.
2010 [cited 2022 Aug 12];7(1 Pt 1):156–65. Available from: https:// Available from: https://pubmed.ncbi.nlm.nih.gov/18260771/
pubmed.ncbi.nlm.nih.gov/19694925/ 862. Kovatchev BP. Diabetes technology: markers, monitoring, assess-
848. Anwar Z, Sinha V, Mitra S, Mishra AK, Ansari MH, Bharti A, et al. ment, and control of blood glucose fluctuations in diabetes. Scientifica
Erectile Dysfunction: An Underestimated Presentation in Patients with (Cairo) [Internet]. 2012 [cited 2022 Aug 10];2012:1–14. Available from:
Diabetes Mellitus. Indian J Psychol Med [Internet]. 2017 Sep 1 [cited https://pubmed.ncbi.nlm.nih.gov/24278682/
2022 Aug 12];39(5):600–4. Available from: https:// 863. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes
pubmed.ncbi.nlm.nih.gov/29200555/ Mellitus Abbreviated Report of a WHO Consultation. 2011;
849. A Study to Evaluate the Effect of Testosterone Replacement 864. Golden S, Boulware LE, Berkenblit G, Brancati F, Chander G,
Therapy (TRT) on the Incidence of Major Adverse Cardiovascular Marinopoulos S. Use of glycated hemoglobin and microalbuminuria in
Events (MACE) and Efficacy Measures in Hypogonadal Men - Full the monitoring of diabetes mellitus. Evid Rep Technol Assess (Summ).
Text View - ClinicalTrials.gov [Internet]. [cited 2022 Aug 22]. 2003;1–6.
Available from: https://clinicaltrials.gov/ct2/show/NCT03518034 865. Gangopadhyay KK, Singh P. Consensus Statement on Dose
850. Cipriani S, Simon JA. Sexual Dysfunction as a Harbinger of Modifications of Antidiabetic Agents in Patients with Hepatic
Cardiovascular Disease in Postmenopausal Women: How Far Are We? Impairment. Indian J Endocrinol Metab [Internet]. 2017 Mar 1 [cited
J Sex Med [Internet]. 2022 Jul [cited 2022 Aug 22]; Available from: 2022 Aug 10];21(2):341–54. Available from: https://
851. Desai A, Chen R, Cayetano A, Jayasena CN, Minhas S. 866. Kirk JK, Stegner J. Self-monitoring of blood glucose: practical as-
Understanding and treating ejaculatory dysfunction in men with pects. J Diabetes Sci Technol [Internet]. 2010 [cited 2022
Diabetes mellitus. Aug 10];4(2):435–9. Available from: https://pubmed.ncbi.nlm.nih.gov/
852. Esposito K, Maiorino MI, Bellastella G, Giugliano F, Romano M, 20307405/
Giugliano D. Determinants of female sexual dysfunction in type 2 diabe- 867. Bailey TS, Grunberger G, Bode BW, Handelsman Y, Hirsch IB,
tes. Int J Impot Res [Internet]. 2010 May [cited 2022 Aug 12];22(3):179– Jovanovič L, et al. AMERICAN ASSOCIATION OF CLINICAL
84. Available from: https://pubmed.ncbi.nlm.nih.gov/20376056/ ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF
853. Barbagallo F, Mongioì LM, Cannarella R, Vignera S la, Condorelli ENDOCRINOLOGY 2016 OUTPATIENT GLUCOSE
RA, Calogero AE. Sexual Dysfunction in Diabetic Women: An Update MONITORING CONSENSUS STATEMENT. Endocr Pract [Internet].
on Current Knowledge. Diabetology 2020, Vol 1, Pages 11-21 [Internet]. 2016 Feb 1 [cited 2022 Aug 10];22(2):231–61. Available from: https://
2020 Sep 10 [cited 2022 Aug 26];1(1):11–21. Available from: https:// pubmed.ncbi.nlm.nih.gov/26848630/
www.mdpi.com/2673-4540/1/1/2/htm 868. Klonoff DC, Buckingham B, Christiansen JS, Montori VM,
854. Shifren JL, Monz BU, Russo PA, Segreti A, Johannes CB. Sexual Tamborlane W v., Vigersky RA, et al. Continuous glucose monitoring:
problems and distress in United States women: prevalence and correlates. an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol
Obstetrics and gynecology [Internet]. 2008 Nov [cited 2022 Metab [Internet]. 2011 [cited 2022 Aug 10];96(10):2968–79. Available
Aug 26];112(5):970–8. Available from: https:// from: https://pubmed.ncbi.nlm.nih.gov/21976745/
pubmed.ncbi.nlm.nih.gov/18978095/ 869. Healy SJ, Dungan KM. Monitoring glycemia in diabetes. Med Clin
855. Dennerstein L, Koochaki P, Barton I, Graziottin A. Hypoactive North Am [Internet]. 2015 Jan 1 [cited 2022 Aug 10];99(1):35–45.
sexual desire disorder in menopausal women: a survey of Western Available from: https://pubmed.ncbi.nlm.nih.gov/25456642/
European women. J Sex Med [Internet]. 2006 [cited 2022 870. Khadilkar KS, Bandgar T, Shivane V, Lila A, Shah N. Current
Aug 26];3(2):212–22. Available from: https://pubmed.ncbi.nlm.nih.gov/ concepts in blood glucose monitoring. Indian J Endocrinol Metab
16490014/ [Internet]. 2013 [cited 2022 Aug 10];17(Suppl 3):S643. Available from:
856. Bąk E, Marcisz C, Krzemińska S, Dobrzyn-Matusiak D, Foltyn A, /pmc/articles/PMC4046592/
Drosdzol-Cop A. Relationships of Sexual Dysfunction with Depression 871. Schnell O, Hanefeld M, Monnier L. Self-monitoring of blood glu-
and Acceptance of Illness in Women and Men with Type 2 Diabetes cose: a prerequisite for diabetes management in outcome trials. J Diabetes
Sci Technol [Internet]. 2014 [cited 2022 Aug 10];8(3):609–14. Available significantly improves glycemic control in patients with type 2 diabetes
from: https://pubmed.ncbi.nlm.nih.gov/24876626/ mellitus after 12 weeks: a randomized, controlled pilot study. Diabetol
872. Mansouri DA, Hasan Alawi H, Barasyn KB, Bnnounh MN, Haddad Metab Syndr [Internet]. 2015 Jan 15 [cited 2022 Aug 10];7(1). Available
NT, Al-Hafdey DA, et al. Self-monitoring of blood glucose among dia- from: https://pubmed.ncbi.nlm.nih.gov/25904987/
betic patients attending Al-Eskan Primary Health Care Center in Makkah 886. Kibriya MG, Ali L, Banik NG, Azad Khan AK. Home monitoring of
Al-Mukarramah city. International Journal of Medical Science and Public blood glucose (HMBG) in Type-2 diabetes mellitus in a developing
Health | [Internet]. 2015 [cited 2022 Aug 10];527. Available from: http:// country. Diabetes Res Clin Pract [Internet]. 1999 Dec [cited 2022
www.ijmsph.com Aug 10];46(3):253–7. Available from: https://pubmed.ncbi.nlm.nih.gov/
873. Karter AJ, Ferrara A, Darbinian JA, Ackerson LM, Selby J v. Self- 10624792/
monitoring of blood glucose: language and financial barriers in a man- 887. Mast O, Tan A, Punjabi K. Usage of Self-Monitoring of Blood
aged care population with diabetes. Diabetes Care [Internet]. 2000 [cited Glucose (Smbg) By Diabetes Therapy Type in India. Value in Health.
2022 Aug 10];23(4):477–83. Available from: https:// 2014 Nov;17(7):A362.
pubmed.ncbi.nlm.nih.gov/10857938/ 888. Garg S, Zisser H, Schwartz S, Bailey T, Kaplan R, Ellis S, et al.
874. Shrivastava SRBL, Shrivastava PS, Ramasamy J. Role of self-care Improvement in glycemic excursions with a transcutaneous, real-time
in management of diabetes mellitus. J Diabetes Metab Disord [Internet]. continuous glucose sensor: a randomized controlled trial. Diabetes Care
2013 Mar 5 [cited 2022 Aug 10];12(1):1. Available from: /pmc/articles/ [Internet]. 2006 [cited 2022 Aug 10];29(1):44–50. Available from:
PMC3599009/ https://pubmed.ncbi.nlm.nih.gov/16373894/
875. Larsen ML, Horder M, Mogensen EF. Effect of long-term monitor- 889. Aschner P, Adler A, Bailey C, Frcpath E, Colagiuri S, Day C, et al.
ing of glycosylated hemoglobin levels in insulin-dependent diabetes IDF Clinical Practice Recommendations for managing Type 2 Diabetes
mellitus. N Engl J Med [Internet]. 1990 [cited 2022 in Primary Care Chair: Core Contributors [Internet]. The Chinese; 2016.
Aug 10];323(15):29. Available from: https://pubmed.ncbi.nlm.nih.gov/ Available from: www.idf.org/managing-type2-diabetes
2215560/ 890. Chowdhury S, Ji L, Suwanwalaikorn S, Yu NC, Tan EK. Practical
876. Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. approaches for self-monitoring of blood glucose: an Asia-Pacific perspec-
Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic tive. Curr Med Res Opin [Internet]. 2015 Mar 1 [cited 2022
Patients. Biomark Insights [Internet]. 2016 Jul 3 [cited 2022 Aug 10];31(3):461–76. Available from: https://
Aug 10];11:95–104. Available from: https://pubmed.ncbi.nlm.nih.gov/ pubmed.ncbi.nlm.nih.gov/25629789/
27398023/ 891. Unnikrishnan R, Mohan V. Suggested Protocols for Self-Monitoring
877. DM N, S G, J L, P C, O C, M D, et al. The effect of intensive of Blood Glucose in India. The Association of Physicians of India.
treatment of diabetes on the development and progression of long-term 2013;194–7.
complications in insulin-dependent diabetes mellitus. N Engl J Med 892. Chawla M, Saboo B, Jha S, Bhandari S, Kumar P, Kesavadev J, et al.
[Internet]. 1993 Sep 30 [cited 2022 Aug 10];329(14):977–86. Available Consensus and recommendations on continuous glucose monitoring.
from: https://pubmed.ncbi.nlm.nih.gov/8366922/ Journal of Diabetology [Internet]. 2019 [cited 2022 Aug 10];10(1):4.
878. Heisler M, Piette JD, Spencer M, Kieffer E, Vijan S. The relationship Available from: https://www.journalofdiabetology.org/
between knowledge of recent HbA1c values and diabetes care under- a r t i c l e . a s p ? i s s n = 2 0 7 8 -
standing and self-management. Diabetes Care [Internet]. 2005 Apr [cited 7685;year=2019;volume=10;issue=1;spage=4;epage=14;aulast=Chawla
2022 Aug 10];28(4):816–22. Available from: https:// 893. Mohan V, Jain S, Kesavadev J, Chawla M, Mutha A, Viswanathan
pubmed.ncbi.nlm.nih.gov/15793179/ V, et al. Use of Retrospective Continuous Glucose Monitoring for
879. Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ. Optimizing Management of Type 2 Diabetes in India. J Assoc
Translating the A1C assay into estimated average glucose values. Physicians India. 2016 Apr;64(4):16–21.
Diabetes Care [Internet]. 2008 Aug [cited 2022 Aug 10];31(8):1473–8. 894. Kesavadev J, Vigersky R, Shin J, Pillai PBS, Shankar A, Sanal G,
Available from: https://pubmed.ncbi.nlm.nih.gov/18540046/ et al. Assessing the Therapeutic Utility of Professional Continuous
880. Betônico CCR, Titan SMO, Correa-Giannella MLC, Nery M, Glucose Monitoring in Type 2 Diabetes Across Various Therapies: A
Queiroz M. Management of diabetes mellitus in individuals with chronic Retrospective Evaluation. Adv Ther [Internet]. 2017 Aug 1 [cited 2022
kidney disease: therapeutic perspectives and glycemic control. Clinics Aug 10];34(8):1918–27. Available from: https://
(Sao Paulo) [Internet]. 2016 Jan 1 [cited 2022 Aug 10];71(1):47–53. pubmed.ncbi.nlm.nih.gov/28667580/
Available from: https://pubmed.ncbi.nlm.nih.gov/26872083/ 895. Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T,
881. Sacks DB. Hemoglobin variants and hemoglobin A1c analysis: et al. Clinical Targets for Continuous Glucose Monitoring Data
problem solved? Clin Chem [Internet]. 2003 Aug 1 [cited 2022 Interpretation: Recommendations From the International Consensus on
Aug 10];49(8):1245–7. Available from: https:// Time in Range. Diabetes Care [Internet]. 2019 Aug 1 [cited 2022
pubmed.ncbi.nlm.nih.gov/12881436/ Aug 12];42(8):1593–603. Available from: https://
882. Rajagopal L, Ganapathy S, Arunachalam S, Raja V, Ramraj B. Does pubmed.ncbi.nlm.nih.gov/31177185/
Iron Deficiency Anaemia and its Severity Influence HbA1C Level in Non 896. Saboo B, Kesavadev J, Shankar A, Krishna MB, Sheth S, Patel V,
Diabetics? An Analysis of 150 Cases. J Clin Diagn Res [Internet]. 2017 et al. Time-in-range as a target in type 2 diabetes: An urgent need.
[cited 2022 Aug 10];11(2):EC13. Available from: /pmc/articles/ Heliyon [Internet]. 2021 Jan 1 [cited 2022 Aug 12];7(1). Available from:
PMC5376870/ https://pubmed.ncbi.nlm.nih.gov/33506132/
883. Mohan V, Deepa R, Shefali AK, Poongothai S, Monica M, 897. Consensus Statement on Use of Ambulatory Glucose Profile in
Karkuzhali K. Evaluation of One Touch HORIZON–a highly affordable Patients with Type 2 Diabetes Mellitus Receiving Oral Antidiabetic
glucose monitor. J Assoc Physicians India. 2004 Oct;52:779–82. Drugs - PubMed [Internet]. [cited 2022 Aug 12]. Available from:
884. Shaji S, Rajendran D, Kumpatla S, Viswanathan V. Evaluation of https://pubmed.ncbi.nlm.nih.gov/31793278/
diabetes self-care with self-monitoring of blood glucose among type 2 898. Kesavadev J, Misra A, Saboo B, Agarwal S, Sosale A, Joshi SR,
diabetic patients and its impact on HbA1c. International Journal of et al. Time-in-range and frequency of continuous glucose monitoring:
Diabetes in Developing Countries 2013 33:3 [Internet]. 2013 Jul 14 [cited Recommendations for South Asia. Diabetes Metab Syndr [Internet].
2022 Aug 10];33(3):181–2. Available from: https://link.springer.com/ar- 2022 Jan 1 [cited 2022 Aug 12];16(1). Available from: https://
ticle/10.1007/s13410-013-0118-2 pubmed.ncbi.nlm.nih.gov/34920199/
885. Silva DDR, Bosco AA. An educational program for insulin self- 899. Rao P v., Makkar BM, Kumar A, Das AK, Singh AK, Mithal A,
adjustment associated with structured self-monitoring of blood glucose et al. RSSDI consensus on self-monitoring of blood glucose in types 1
and 2 diabetes mellitus in India. Int J Diabetes Dev Ctries [Internet]. 2018 www.fda.gov/regulatory-information/search-fda-guidance-documents/
Sep 1 [cited 2022 Aug 12];38(3):260–79. Available from: https:// self-monitoring-blood-glucose-test-systems-over-counter-use
link.springer.com/article/10.1007/s13410-018-0677-3 914. Blood Glucose Monitoring Test Systems for Prescription Point-of-
900. Kesavadev J, Sadikot S, Wangnoo S, Kannampilly J, Saboo B, Care Use | FDA [Internet]. [cited 2022 Aug 12]. Available from: https://
Aravind SR, et al. Consensus guidelines for glycemic monitoring in type www.fda.gov/regulatory-information/search-fda-guidance-documents/
1/type 2 & GDM. Diabetes Metab Syndr [Internet]. 2014 Jul 1 [cited blood-glucose-monitoring-test-systems-prescription-point-care-use
2022 Aug 12];8(3):187–95. Available from: https:// 915. 7. Diabetes Technology: Standards of Medical Care in Diabetes-
pubmed.ncbi.nlm.nih.gov/25200925/ 2 0 1 9 . D i a b e t e s C a r e [I n t e r ne t ] . 2 0 1 9 J a n 1 [ c i t e d 2 0 2 2
901. Bergenstal RM, Gavin JR. The role of self-monitoring of blood Aug 12];42(Suppl 1):S71–80. Available from: https://
glucose in the care of people with diabetes: report of a global consensus pubmed.ncbi.nlm.nih.gov/30559233/
conference. Am J Med [Internet]. 2005 [cited 2022 Aug 12];118(Suppl 916. Chawla M, Saboo B, Jha S, Bhandari S, Kumar P, Kesavadev J, et al.
9A):1–6. Available from: https://pubmed.ncbi.nlm.nih.gov/16224936/ Consensus and recommendations on continuous glucose monitoring.
902. Clarke SF, Foster JR. A history of blood glucose meters and their Journal of Diabetology [Internet]. 2022 [cited 2022 Sep 1];10(1):4.
role in self-monitoring of diabetes mellitus. . Br J Biomed Sci. Available from: https://www.journalofdiabetology.org/
2012;69:83-93. a r t i c l e . a s p ? i s s n = 2 0 7 8 -
903. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10- 7685;year=2019;volume=10;issue=1;spage=4;epage=14;aulast=Chawla
year follow-up of intensive glucose control in type 2 diabetes. N Engl J 917. Wagner J, Tennen H, Wolpert H. Continuous glucose monitoring: a
Med [Internet]. 2008 Oct 9 [cited 2022 Aug 12];359(15):1577–89. review for behavioral researchers. Psychosom Med [Internet]. 2012 [cited
Available from: https://pubmed.ncbi.nlm.nih.gov/18784090/ 2022 Sep 1];74(4):356–65. Available from: https://
904. DM N, S G, J L, P C, O C, M D, et al. The effect of intensive pubmed.ncbi.nlm.nih.gov/22582333/
treatment of diabetes on the development and progression of long-term 918. Kesavadev J, Jain SM, Muruganathan A, Das AK, Diabetes
complications in insulin-dependent diabetes mellitus. N Engl J Med Consensus Group. Consensus evidence-based guidelines for use of insu-
[Internet]. 1993 Sep 30 [cited 2022 Aug 12];329(14):977–86. Available lin pump therapy in the management of diabetes as per Indian clinical
from: https://pubmed.ncbi.nlm.nih.gov/8366922/ practice. J Assoc Physicians India. 2014 Jul;62(7 Suppl):34–41.
905. Nathan DM. The diabetes control and complications trial/ 919. Kesavadev J, Das AK, Unnikrishnan RI, Joshi SR, Ramachandran
epidemiology of diabetes interventions and complications study at 30 A, Shamsudeen J, et al. Use of Insulin Pumps in India: Suggested
years: overview. Diabetes Care [Internet]. 2014 Jan [cited 2022 Guidelines Based on Experience and Cultural Differences. Diabetes
Aug 12];37(1):9–16. Available from: https://pubmed.ncbi.nlm.nih.gov/ Technol Ther [Internet]. 2010 Oct 1 [cited 2022 Sep 1];12(10):823.
24356592/ Available from: /pmc/articles/PMC2956384/
906. Franciosi M, Lucisano G, Pellegrini F, Cantarello A, Consoli A, 920. Kesavadev J, Sadasivan Pillai PB, Shankar A, Warrier RS,
Cucco L, et al. ROSES: role of self-monitoring of blood glucose and Ramachandran L, Jothydev S, et al. Exploratory CSII Randomized
intensive education in patients with Type 2 diabetes not receiving insulin. Controlled Trial on Erectile Dysfunction in T2DM Patients
A pilot randomized clinical trial. Diabet Med [Internet]. 2011 Jul [cited (ECSIITED). J Diabetes Sci Technol. 2018;12(6):1252–3.
2022 Aug 12];28(7):789–96. Available from: https:// 921. Kesavadev J, Balakrishnan S, Ahammed S, Jothydev S. Reduction
pubmed.ncbi.nlm.nih.gov/21342243/ of glycosylated hemoglobin following 6 months of continuous subcuta-
907. Polonsky WH, Fisher L, Schikman CH, Hinnen DA, Parkin CG, neous insulin infusion in an Indian population with type 2 diabetes.
Jelsovsky Z, et al. Structured self-monitoring of blood glucose signifi- Diabetes Technol Ther. 2009 Aug;11(8):517–21.
cantly reduces A1C levels in poorly controlled, noninsulin-treated type 2 922. Kesavadev J, Shankar A, Babu Sadasivan Pillai P, Saboo B, Joshi S,
diabetes: results from the Structured Testing Program study. Diabetes Krishnan G. CSII as an Alternative Therapeutic Strategy for
Care [Internet]. 2011 Feb [cited 2022 Aug 12];34(2):262–7. Available ManagingType 2 Diabetes: Adding the Indian Experience to a Global
from: https://pubmed.ncbi.nlm.nih.gov/21270183/ Perspective. Curr Diabetes Rev [Internet]. 2016.
908. Kato N, Cui J, Kato M. Structured self-monitoring of blood glucose 923. Association AD. Standards of Medical Care in Diabetes—2022
reduces glycated hemoglobin in insulin-treated diabetes. J Diabetes Abridged for Primary Care Providers. Clinical Diabetes [Internet]. 2022
Investig [Internet]. 2013 Sep [cited 2022 Aug 12];4(5):450–3. Jan 1 [cited 2022 Sep 1];40(1):10–38. Available from: https://
Available from: https://pubmed.ncbi.nlm.nih.gov/24843694/ diabetesjournals.org/clinical/article/40/1/10/139035/Standards-of-
909. Kempf K, Kruse J, Martin S. ROSSO-in-praxi follow-up: long-term Medical-Care-in-Diabetes-2022
effects of self-monitoring of blood glucose on weight, hemoglobin A1c, 924. Saboo BD, Talaviya PA. Continuous subcutaneous insulin infusion:
and quality of life in patients with type 2 diabetes mellitus. Diabetes practical issues. Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S259-
Technol Ther [Internet]. 2012 Jan 1 [cited 2022 Aug 12];14(1):59–64. 62.
Available from: https://pubmed.ncbi.nlm.nih.gov/21988274/ 925. Grunberger G, Sherr J, Allende M, Blevins T, Bode B, Handelsman
910. Miller KM, Beck RW, Bergenstal RM, Goland RS, Haller MJ, Y, et al. American Association of Clinical Endocrinology Clinical
McGill JB, et al. Evidence of a strong association between frequency of Practice Guideline: The Use of Advanced Technology in the
self-monitoring of blood glucose and hemoglobin A1c levels in T1D Management of Persons With Diabetes Mellitus. Endocr Pract.
exchange clinic registry participants. Diabetes Care [Internet]. 2013 [cited 2021;27(6):505–37.
2022 Aug 12];36(7):2009–14. Available from: https:// 926. Kesavadev J, Srinivasan S, Saboo B, Krishna B M, Krishnan G. The
pubmed.ncbi.nlm.nih.gov/23378621/ Do-It-Yourself Artificial Pancreas: A Comprehensive Review. Diabetes
911. Blood Glucose Monitoring Devices | FDA [Internet]. [cited 2022 Ther [Internet]. 2020 Jun 1 [cited 2022 Sep 1];11(6):1217–35. Available
Aug 12]. Available from: https://www.fda.gov/medical-devices/in-vitro- from: https://pubmed.ncbi.nlm.nih.gov/32356245/
diagnostics/blood-glucose-monitoring-devices 927. Kesavadev J, Saboo B, Kar P, Sethi J. DIY artificial pancreas: A
912. ISO - ISO 15197:2013 - In vitro diagnostic test systems — narrative of the first patient and the physicians’ experiences from India.
Requirements for blood-glucose monitoring systems for self-testing in Diabetes Metab Syndr [Internet]. 2021 Mar 1 [cited 2022 Sep
managing diabetes mellitus [Internet]. [cited 2022 Aug 12]. Available 1];15(2):615–20. Available from: https://pubmed.ncbi.nlm.nih.gov/
from: https://www.iso.org/standard/54976.html 33725629/
913. Self-Monitoring Blood Glucose Test Systems for Over-the-Counter 928. Anhalt H, Bohannon NJV. Insulin patch pumps: their development
Use | FDA [Internet]. [cited 2022 Aug 12]. Available from: https:// and future in closed-loop systems. Diabetes Technol Ther [Internet]. 2010
[cited 2022 Aug 12];12 Suppl 1(Suppl 1). Available from: https:// 944. Vigersky RA. The benefits, limitations, and cost-effectiveness of
pubmed.ncbi.nlm.nih.gov/20515308/ advanced technologies in the management of patients with diabetes
929. Ginsberg BH. Patch Pumps for Insulin. J Diabetes Sci Technol mellitus. J Diabetes Sci Technol [Internet]. 2015 Mar 1 [cited 2022 Sep
[Internet]. 2019 Jan 1 [cited 2022 Aug 12];13(1):27–33. Available from: 1];9(2):320–30. Available from: https://pubmed.ncbi.nlm.nih.gov/
https://pubmed.ncbi.nlm.nih.gov/30070604/ 25555391/
930. Kesavadev J, Shankar A, David Ashok A. Free Insulin Pumps to 945. Kesavadev J, Krishnan G, Mohan V. Digital health and diabetes:
Type 1 Diabetes Children- KT1DP Initiative. . Abu Dhabi: International experience from India. Ther Adv Endocrinol Metab. 2021
Diabetes Federation 2017 Congress; 2017. Jan 17;12:204201882110546.
931. Association AD. 1. Improving Care and Promoting Health in 946. Ramakrishnan P, Yan K, Balijepalli C, Druyts E. Changing face of
Populations: Standards of Medical Care in Diabetes—2019. Diabetes healthcare: digital therapeutics in the management of diabetes. Curr Med
Care [Internet]. 2019 Jan 1 [cited 2022 Aug 12];42(Supplement_1):S7– Res Opin. 2021;37(12):2089–91.
12. Available from: https://diabetesjournals.org/care/article/42/ 947. mHealth: Mobile Technology Poised to Enable a New Era in Health
Supplement_1/S7/31070/1-Improving-Care-and-Promoting-Health-in Care. Ernst & Young; 2012.
932. Tricco AC, Ivers NM, Grimshaw JM, Moher D, Turner L, Galipeau 948. Davidson J, Wilkinson A, Dantal J, Dotta F, Haller H, Hernández D,
J et al. Effectiveness of quality improvement strategies on the manage- et al. New-onset diabetes after transplantation: 2003 International consen-
ment of diabetes: A systematic review and meta-analysis. . Lancet. sus guidelines. Proceedings of an international expert panel meeting.
2012;379:2252–61. Barcelona, Spain, 19 February 2003. Transplantation [Internet]. 2003
933. Cebul RD, Love TE, Jain AK, Hebert CJ. Electronic health records May 27 [cited 2022 Aug 13];75(10 Suppl). Available from: https://
and quality of diabetes care. N Engl J Med [Internet]. 2011 Sep [cited pubmed.ncbi.nlm.nih.gov/12775942/
2022 Aug 12];365(9):825–33. Available from: https:// 949. Association AD. Standards of Medical Care in Diabetes—2011.
pubmed.ncbi.nlm.nih.gov/21879900/ Diabetes Care [Internet]. 2011 Jan 1 [cited 2022
934. Battersby M, von Korff M, Schaefer J, Davis C, Ludman E, Greene Aug 13];34(Supplement_1):S11–61. Available from: https://
SM, et al. Twelve evidence-based principles for implementing self- diabetesjournals.org/care/article/34/Supplement_1/S11/25857/
management support in primary care. Jt Comm J Qual Patient Saf Standards-of-Medical-Care-in-Diabetes-2011
[Internet]. 2010 [cited 2022 Aug 12];36(12):561–70. Available from: 950. Sharif A, Hecking M, de Vries APJ, Porrini E, Hornum M, Rasoul-
https://pubmed.ncbi.nlm.nih.gov/21222358/ Rockenschaub S, et al. Proceedings from an international consensus
935. Jia P, Zhao P, Chen J, Zhang M. Evaluation of clinical decision meeting on posttransplantation diabetes mellitus: recommendations and
support systems for diabetes care: An overview of current evidence. J future directions. Am J Transplant [Internet]. 2014 [cited 2022
Eval Clin Pract [Internet]. 2019 Feb 1 [cited 2022 Aug 12];25(1):66– Aug 13];14(9):1992–2000. Available from: https://
77. Available from: https://pubmed.ncbi.nlm.nih.gov/29947136/ pubmed.ncbi.nlm.nih.gov/25307034/
936. Bright TJ, Wong A, Dhurjati R, Bristow E, Bastian L, Coeytaux RR, 951. Gupta S, Pollack T, Fulkerson C, Schmidt K, Oakes DJ, Molitch
et al. Effect of clinical decision-support systems: a systematic review. ME, et al. Hyperglycemia in the Posttransplant Period: NODAT vs
Ann Intern Med [Internet]. 2012 [cited 2022 Aug 12];157(1):29–43. Posttransplant Diabetes Mellitus. J Endocr Soc [Internet]. 2018 Nov 11
Available from: https://pubmed.ncbi.nlm.nih.gov/22751758/ [cited 2022 Aug 13];2(11):1314. Available from: /pmc/articles/
937. American Telemedicine Association. About Telemedicine. PMC6223248/
Available from: http://www.americantelemed.org/main/about/ 952. Wilkinson A, Davidson J, Dotta F, Home PD, Keown P, Kiberd B,
abouttelemedicine/ telemedicine-faqs. [Last accessed on 2022 Aug 12]. et al. Guidelines for the treatment and management of new-onset diabetes
938. Xu T, Pujara S, Sutton S, Rhee M. Telemedicine in the Management after transplantation. Clin Transplant [Internet]. 2005 Jun [cited 2022
of Type 1 Diabetes. Prev Chronic Dis [Internet]. 2018 [cited 2022 Aug 13];19(3):291–8. Available from: https://pubmed.ncbi.nlm.nih.gov/
Aug 12];15(1). Available from: https://pubmed.ncbi.nlm.nih.gov/ 15877787/
29369757/ 953. Chakkera HA, Weil EJ, Pham PT, Pomeroy J, Knowler WC. Can
939. Lee SWH, Chan CKY, Chua SS, Chaiyakunapruk N. Comparative New-Onset Diabetes After Kidney Transplant Be Prevented? Diabetes
effectiveness of telemedicine strategies on type 2 diabetes management: Care [Internet]. 2013 May [cited 2022 Aug 13];36(5):1406. Available
A systematic review and network meta-analysis. Sci Rep [Internet]. 2017 from: /pmc/articles/PMC3631828/
Dec 1 [cited 2022 Aug 12];7(1). Available from: /pmc/articles/ 954. Sharif A, Moore R, Baboolal K. Influence of lifestyle modification
PMC5627243/ in renal transplant recipients with postprandial hyperglycemia.
940. Marcolino MS, Maia JX, Alkmim MBM, Boersma E, Ribeiro AL. Transplantation [Internet]. 2008 Feb [cited 2022 Aug 13];85(3):353–8.
Telemedicine application in the care of diabetes patients: systematic re- Available from: https://pubmed.ncbi.nlm.nih.gov/18301331/
view and meta-analysis. PLoS One [Internet]. 2013 Nov 8 [cited 2022 955. Hecking M, Haidinger M, Döller D, Werzowa J, Tura A, Zhang J,
Aug 12];8(11). Available from: https://pubmed.ncbi.nlm.nih.gov/ et al. Early basal insulin therapy decreases new-onset diabetes after renal
24250826/ transplantation. J Am Soc Nephrol [Internet]. 2012 Apr [cited 2022
941. Heitkemper EM, Mamykina L, Travers J, Smaldone A. Do health Aug 13];23(4):739–49. Available from: https://
information technology self-management interventions improve glyce- pubmed.ncbi.nlm.nih.gov/22343119/
mic control in medically underserved adults with diabetes? A systematic 956. Yates CJ, Fourlanos S, Hjelmesæth J, Colman PG, Cohney SJ. New-
review and meta-analysis. J Am Med Inform Assoc [Internet]. 2017 Sep 1 onset diabetes after kidney transplantation-changes and challenges. Am J
[cited 2022 Aug 12];24(5). Available from: https:// Transplant [Internet]. 2012 Apr [cited 2022 Aug 13];12(4):820–8.
942. Kesavadev J, Shankar A, Pillai PBS, Krishnan G, Jothydev S. Cost- 957. Hecking M, Werzowa J, Haidinger M, Hörl WH, Pascual J, Budde
effective use of telemedicine and self-monitoring of blood glucose via K, et al. Novel views on new-onset diabetes after transplantation: devel-
Diabetes Tele Management System (DTMS) to achieve target glycosyl- opment, prevention and treatment. Nephrol Dial Transplant [Internet].
ated hemoglobin values without serious symptomatic hypoglycemia in 2013 Mar [cited 2022 Aug 13];28(3):550–66. Available from: https://
1,000 subjects with type 2 diabetes mellitus–a retrospective study. pubmed.ncbi.nlm.nih.gov/23328712/
Diabetes Technol Ther [Internet]. 2012 Sep 1 [cited 2022 958. Association AD. Standards of Medical Care in Diabetes—2013.
Aug 12];14(9):772–6. Available from: https://pubmed.ncbi.nlm.nih.gov/ Diabetes Care [Internet]. 2013 Jan 1 [cited 2022
22734662/ Aug 13];36(Supplement_1):S11–66. Available from: https://
943. National Digital Health Mission Strategy Overview. 2020;
diabetesjournals.org/care/article/36/Supplement_1/S11/27342/ 974. Garg MK, Gopalakrishnan M, Yadav P, Misra S. Endocrine

Standards-of-Medical-Care-in-Diabetes-2013 Involvement in COVID-19: Mechanisms, Clinical Features, and
959. Werzowa J, Hecking M, Haidinger M, Lechner F, Döller D, Pacini Implications for Care. Indian J Endocrinol Metab [Internet]. 2020 Sep 1
G, et al. Vildagliptin and pioglitazone in patients with impaired glucose [cited 2022 Aug 13];24(5):381–6. Available from: https://
tolerance after kidney transplantation: a randomized, placebo-controlled pubmed.ncbi.nlm.nih.gov/33489841/
clinical trial. Transplantation [Internet]. 2013 Feb 15 [cited 2022 975. Bozkurt B, Kovacs R, Harrington B. Joint HFSA/ACC/AHA
Aug 13];95(3):456–62. Available from: https:// Statement Addresses Concerns Re: Using RAAS Antagonists in
pubmed.ncbi.nlm.nih.gov/23380864/ COVID-19. J Card Fail [Internet]. 2020 May 1 [cited 2022
960. Sharif A. Should metformin be our antiglycemic agent of choice Aug 13];26(5):370. Available from: /pmc/articles/PMC7234783/
post-transplantation? Am J Transplant [Internet]. 2011 Jul [cited 2022 976. Schlesinger S, Neuenschwander M, Lang A, Pafili K, Kuss O,
Aug 13];11(7):1376–81. Available from: https:// Herder C, et al. Risk phenotypes of diabetes and association with
pubmed.ncbi.nlm.nih.gov/21564529/ COVID-19 severity and death: a living systematic review and meta-ana-
961. Lalau JD, Arnouts P, Sharif A, de Broe ME. Metformin and other lysis. Diabetologia [Internet]. 2021 Jul 1 [cited 2022
antidiabetic agents in renal failure patients. Kidney Int [Internet]. 2015 Aug 13];64(7):1480–91. Available from: https://
Feb 3 [cited 2022 Aug 13];87(2):308–22. Available from: https:// pubmed.ncbi.nlm.nih.gov/33907860/
pubmed.ncbi.nlm.nih.gov/24599253/ 977. Kumar B, Mittal M, Gopalakrishnan M, Garg MK, Misra S. Effect
962. Pascual J, Royuela A, Galeano C, Crespo M, Zamora J. Very early of plasma glucose at admission on COVID-19 mortality: experience from
steroid withdrawal or complete avoidance for kidney transplant recipi- a tertiary hospital. Endocr Connect [Internet]. 2021 [cited 2022
ents: a systematic review. Nephrol Dial Transplant [Internet]. 2012 Feb Aug 13];10(6):589–98. Available from: https://
pubmed.ncbi.nlm.nih.gov/21785040/ 978. Lazarus G, Audrey J, Wangsaputra VK, Tamara A, Tahapary DL.
963. Pascual J, Galeano C, Royuela A, Zamora J. A systematic review on High admission blood glucose independently predicts poor prognosis in
steroid withdrawal between 3 and 6 months after kidney transplantation. COVID-19 patients: A systematic review and dose-response meta-ana-
Transplantation [Internet]. 2010 Aug 27 [cited 2022 Aug 13];90(4):343– lysis. Diabetes Res Clin Pract [Internet]. 2021 Jan 1 [cited 2022
9. Available from: https://pubmed.ncbi.nlm.nih.gov/20574419/ Aug 13];171. Available from: https://pubmed.ncbi.nlm.nih.gov/
964. Peev V, Reiser J, Alachkar N. Diabetes Mellitus in the Transplanted 33310127/
Kidney. Front Endocrinol (Lausanne) [Internet]. 2014 [cited 2022 9 7 9 .
Aug 13];5(AUG). Available from: /pmc/articles/PMC4145713/ ClinicalGuidanceonDiagnosisandManagementofDiabetesatCOVID19P-
965. Shivaswamy V, Boerner B, Larsen J. Post-Transplant Diabetes atientManagementfacility.pdf [Internet]. [cited 2022 Aug 4]. Available
Mellitus: Causes, Treatment, and Impact on Outcomes. Endocr Rev from: https://www.mohfw.gov.in/pdf/
[Internet]. 2016 [cited 2022 Aug 13];37(1):37–61. Available from: ClinicalGuidanceonDiagnosisandManagementofDiabetesatCOVID19P-
https://pubmed.ncbi.nlm.nih.gov/26650437/ atientManagementfacility.pdf - Google Search [Internet]. [cited 2022
966. Boudreaux J, McHugh L, Canafax D, … NA, 1987 undefined. The Aug 13]. Available from: https://www.google.com/
impact of cyclosporine and combination immunosuppression on the in- search?q=ClinicalGuidanceonDiagnosisandManagementofDiabetesatC-
cidence of posttransplant diabetes in renal allograft recipients. OVID19PatientManagementfacility.pdf+%5BInternet%5D.+%5Bcited+
europepmc.org [Internet]. [cited 2022 Aug 13]; Available from: https:// 2022+Aug+4%5D.+Available+from%3A+
europepmc.org/article/med/3307061 https%3A%2F%2Ffanyv88.com%3A443%2Fhttps%2Fwww.mohfw.gov.in%2Fpdf%2FClinicalGuidanceo-
967. Revanur VK, Jardine AG, Kingsmore DB, Jaques BC, Hamilton nDiagnosisandManagementofDiabetesatCOVID19PatientManagementf-
DH, Jindal RM. Influence of diabetes mellitus on patient and graft sur- acility.pdf&oq=ClinicalGuidanceonDiagnosisandManagementofDiabet-
vival in recipients of kidney transplantation. Clin Transplant [Internet]. esatCOVID19PatientManagementfacility.pdf+%5BInternet%5D.+
2001 [cited 2022 Aug 13];15(2):89–94. Available from: https:// %5Bcited+2022+Aug+4%5D.+Available+from%3A+
pubmed.ncbi.nlm.nih.gov/11264633/ https%3A%2F%2Ffanyv88.com%3A443%2Fhttps%2Fwww.mohfw.gov.in%2Fpdf%2FClinicalGuidanceo-
968. WHO Coronavirus (COVID-19) Dashboard [Internet]. [cited 2021 nDiagnosisandManagementofDiabetesatCOVID19PatientManagementf-
Nov 3]. Available from: https://covid19.who.int. acility.pdf&aqs=chrome..69i57.714j0j4&sourceid=chrome&ie=UTF-8
969. Corrao S, Pinelli K, Vacca M, Raspanti M, Argano C. Type 2 980. Gupta Y, Goyal A, Kubihal S, Golla KK, Tandon N. A guidance on
Diabetes Mellitus and COVID-19: A Narrative Review. Front diagnosis and management of hyperglycemia at COVID care facilities in
Endocrinol (Lausanne) [Internet]. 2021 Mar 31 [cited 2022 Aug 13];12. India. Diabetes Metab Syndr [Internet]. 2021 Jan 1 [cited 2022
Available from: /pmc/articles/PMC8044543/ Aug 13];15(1):407–13. Available from: https://europepmc.org/articles/
970. Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: PMC7857082
Prevalence, pathophysiology, prognosis and practical considerations. 981. Coppelli A, Giannarelli R, Aragona M, Penno G, Falcone M, Tiseo
Diabetes Metab Syndr [Internet]. 2020 Jul 1 [cited 2022 G, et al. Hyperglycemia at Hospital Admission Is Associated With
Aug 13];14(4):303–10. Available from: https:// Severity of the Prognosis in Patients Hospitalized for COVID-19: The
pubmed.ncbi.nlm.nih.gov/32298981/ Pisa COVID-19 Study. Diabetes Care [Internet]. 2020 Oct 1 [cited 2022
971. Landstra CP, de Koning EJP. COVID-19 and Diabetes: Aug 13];43(10):2345–8. Available from: https://
Understanding the Interrelationship and Risks for a Severe Course. pubmed.ncbi.nlm.nih.gov/32788285/
Front Endocrinol (Lausanne). 2021 Jun 17;12:599. 982. Fadini GP, Morieri ML, Boscari F, Fioretto P, Maran A, Busetto L,
972. Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, et al. Newly-diagnosed diabetes and admission hyperglycemia predict
Birkenfeld AL, et al. Practical recommendations for the management of COVID-19 severity by aggravating respiratory deterioration. Diabetes
diabetes in patients with COVID-19. Lancet Diabetes Endocrinol Res Clin Pract [Internet]. 2020 Oct 1 [cited 2022 Aug 13];168:108374.
[Internet]. 2020 Jun 1 [cited 2022 Aug 13];8(6):546–50. Available from: Available from: /pmc/articles/PMC7428425/
https://pubmed.ncbi.nlm.nih.gov/32334646/ 983. Mithal A, Jevalikar G, Sharma R, Singh A, Farooqui KJ, Mahendru
973. Apicella M, Campopiano MC, Mantuano M, Mazoni L, Coppelli A, S, et al. High prevalence of diabetes and other comorbidities in hospital-
del Prato S. COVID-19 in people with diabetes: understanding the rea- ized patients with COVID-19 in Delhi, India, and their association with
sons for worse outcomes. Lancet Diabetes Endocrinol [Internet]. 2020 outcomes. Diabetes Metab Syndr [Internet]. 2021 Jan 1 [cited 2022
Sep 1 [cited 2022 Aug 13];8(9):782–92. Available from: https:// Aug 13];15(1):169–75. Available from: https://
984. Singh AK, Singh R. Hyperglycemia without diabetes and new-onset scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Pape+J.+
diabetes are both associated with poorer outcomes in COVID-19. Lower-carb+options.+Diabetes+Health.+
Diabetes Res Clin Pract [Internet]. 2020 Sep 1 [cited 2022 2004%3B13%286%29%3A34.&btnG=
Aug 13];167:108382. Available from: /pmc/articles/PMC7445123/ 1000. Diabetes now–safe travel tips for the diabetic patient (continuing
985. Merzon E, Green I, Shpigelman M, Vinker S, Raz I, Golan-Cohen education credit) - PubMed [Internet]. [cited 2022 Aug 13]. Available
A, et al. Haemoglobin A1c is a predictor of COVID-19 severity in pa- from: https://pubmed.ncbi.nlm.nih.gov/2648549/
tients with diabetes. Diabetes Metab Res Rev [Internet]. 2021 Jul 1 [cited 1001. Westphal SA, Nassar AA, Childs RD. Diabetes self- management
2022 Aug 13];37(5). Available from: https://pubmed.ncbi.nlm.nih.gov/ in the heat. . Pract Diabetol. 2011;21–5.
32852883/ 1002. CLINICARE (INDIA) Launches FRIO ® Insulin Wallet – an
986. Song S, Zhang S, Wang Z, Wang S, Ma Y, Ma P, et al. Association Effective Travel Storage Solution Designed to Keep Insulin Cool |
Between Longitudinal Change in Abnormal Fasting Blood Glucose Flash News Release [Internet]. [cited 2022 Aug 13]. Available from:
Levels and Outcome of COVID-19 Patients Without Previous https://www.mynewsdesk.com/in/flash-news-release/pressreleases/
Diagnosis of Diabetes. Front Endocrinol (Lausanne) [Internet]. 2021 clinicare-india-launches-frio-r-insulin-wallet-an-effective-travel-storage-
Mar 30 [cited 2022 Aug 13];12:640529–640529. Available from: solution-designed-to-keep-insulin-cool-997356
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042381 1003. Casey P. Preparing our patients for travel. . Pract Diabetol.
987. Sadhu AR, Serrano IA, Xu J, Nisar T, Lucier J, Pandya AR, et al. 2011;30(4):26–8.
Continuous Glucose Monitoring in Critically Ill Patients With COVID- 1004. King BR, Goss PW, Paterson MA, Crock PA, Anderson DG.
19: Results of an Emergent Pilot Study. J Diabetes Sci Technol [Internet]. Changes in altitude cause unintended insulin delivery from insulin
2020 [cited 2022 Aug 13];14(6):1065–73. Available from: https:// pumps: Mechanisms and implications. Diabetes Care [Internet]. 2011
pubmed.ncbi.nlm.nih.gov/33063556/ Sep [cited 2022 Aug 13];34(9):1932–3. Available from: /pmc/articles/
988. Faulds ER, Boutsicaris A, Sumner L, Jones L, McNett M, Smetana PMC3161261/
KS, et al. Use of Continuous Glucose Monitor in Critically Ill COVID-19 1005. Hirsch IB. Hitting the dartboard from 40,000 feet. Diabetes
Patients Requiring Insulin Infusion: An Observational Study. J Clin Technol Ther [Internet]. 2011 Oct 1 [cited 2022 Aug 13];13(10):981–2.
Endocrinol Metab [Internet]. 2021 Oct 1 [cited 2022 Available from: https://pubmed.ncbi.nlm.nih.gov/21861590/
Aug 13];106(10):E4007–16. Available from: https:// 1006. Chelminska K, Jaremin B. Travelling diabetics. . Int Marit Health.
pubmed.ncbi.nlm.nih.gov/34100545/ 2002;53(1–4):67–76.
989. Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, et al. Association 1007. Chandran M, Edelman S v. Have Insulin, Will Fly: Diabetes
of Blood Glucose Control and Outcomes in Patients with COVID-19 and Management During Air Travel and Time Zone Adjustment Strategies.
Pre-existing Type 2 Diabetes. Cell Metab [Internet]. 2020 Jun 2 [cited Clinical Diabetes [Internet]. 2003 Apr 1 [cited 2022 Aug 13];21(2):82–5.
2022 Aug 13];31(6):1068-1077.e3. Available from: https:// Available from: https://diabetesjournals.org/clinical/article/21/2/82/571/
pubmed.ncbi.nlm.nih.gov/32369736/ Have-Insulin-Will-Fly-Diabetes-Management-During
990. Bode B, Garrett V, Messler J, McFarland R, Crowe J, Booth R, et al. 1008. Aerospace Medical Association Medical Guidelines Task Force.
Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Medical guidelines for airline travel, 2nd edition. Aviat Space Environ
Hospitalized in the United States. J Diabetes Sci Technol [Internet]. 2020 Med. 2002;74(5):A1–19.
Jul 1 [cited 2022 Aug 13];14(4):813–21. Available from: https:// 1009. Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW.
pubmed.ncbi.nlm.nih.gov/32389027/ Cardiovascular risk factors and venous thromboembolism: a meta ana-
991. Nassar AA, Cook CB, Edelman S. Diabetes management during lysis. Circulation. 2008;117((1):93–102.
travel MANAGEMENT PERSPECTIVE. Diabetes Manage. 1010. Gustaitis J. Taking to the air with diabetes. . Diabetes Self Manag.
2012;2(3):205–12. 2002;19(3):36–7.
992. Burnett JCD. Long- and short-haul travel by air: issues for people 1011. Mirsky S. Vacationing with diabetes, not from diabetes. . . IMS Ind
with diabetes on insulin. undefined. 2006 Sep;13(5):255–60. Med Surg. 1972;41(2):28–30.
993. Dewey CM, Riley WJ. Have diabetes, will travel. http://dx.doi.org/ 1012. Cradock S. The traveller with diabetes: answers to common
103810/pgm199902538 [Internet]. 2015 [cited 2022 queries. . Commun Nurse. 1997;3(4):28–30.
Aug 13];105(2):111–26. Available from: https://www.tandfonline.com/ 1013. Hernandez C. Traveling with diabetes. . Diabetes Self Manag.
doi/abs/10.3810/pgm.1999.02.538 2003;20(6):120–3.
994. Lumber T, forecast PSD, 2005 undefined. Have insulin, will travel. 1014. Suh S, Park MK. Glucocorticoid-Induced Diabetes Mellitus: An
Planning ahead will make traveling with insulin smooth sailing. Important but Overlooked Problem. Endocrinol Metab (Seoul) [Internet].
pubmed.ncbi.nlm.nih.gov [Internet]. [cited 2022 Aug 13]; Available 2017 Jun 1 [cited 2022 Aug 13];32(2):180–9. Available from: https://
from: https://pubmed.ncbi.nlm.nih.gov/16124104/ pubmed.ncbi.nlm.nih.gov/28555464/
995. Westphal SA, Childs RD, Seifert KM, Boyle ME, Fowke M, Iñiguez 1015. Roberts A, James J, Dhatariya K, Agarwal N, Brake J, Brooks C,
P, et al. Managing diabetes in the heat: potential issues and concerns. et al. Management of hyperglycaemia and steroid (glucocorticoid) thera-
Endocr Pract [Internet]. 2010 May [cited 2022 Aug 13];16(3):506–11. py: a guideline from the Joint British Diabetes Societies (JBDS) for
Available from: https://pubmed.ncbi.nlm.nih.gov/20150024/ Inpatient Care group. Diabet Med [Internet]. 2018 Aug 1 [cited 2022
996. Cook CB, Wellik KE, Fowke M. Geoenvironmental diabetology. J Aug 13];35(8):1011–7. Available from: https://
Diabetes Sci Technol [Inter net]. 2011 Jul 1 [cited 2022 pubmed.ncbi.nlm.nih.gov/30152586/
Aug 13];5(4):834–42. Available from: https://journals.sagepub.com/doi/ 1016. Association AD. 2. Classification and Diagnosis of Diabetes:
10.1177/193229681100500402 Standards of Medical Care in Diabetes—2021. Diabetes Care [Internet].
997. Garofano C. Travel tips for the peripatetic diabetic. Nursing (Brux) 2021 Jan 1 [cited 2022 Aug 13];44(Supplement_1):S15–33. Available
[Internet]. 1977 [cited 2022 Aug 13];7(8):44–6. Available from: https:// from: https://diabetesjournals.org/care/article/44/Supplement_1/S15/
pubmed.ncbi.nlm.nih.gov/586516/ 30859/2-Classification-and-Diagnosis-of-Diabetes
998. Eating Well While Traveling - Diabetes Resources & Information | 1017. Rayman G, Lumb AN, Kennon B, Cottrell C, Nagi D, Page E, et al.
Diabetes Self-Management [Internet]. [cited 2022 Aug 13]. Available Dexamethasone therapy in COVID-19 patients: implications and guid-
from: https://www.diabetesselfmanagement.com/diabetes-resources/ ance for the management of blood glucose in people with and without
money-matters/eating-well-while-traveling/ diabetes. Diabet Med [Internet]. 2021 Jan 1 [cited 2022 Aug 13];38(1).
999. Pape J. Lower-carb options. Diabetes Health. 2004;13(6):34. - Available from: https://pubmed.ncbi.nlm.nih.gov/32740972/
Google Scholar [Internet]. [cited 2022 Aug 13]. Available from: https://
1018. Sinclair AJ, Dashora U, George S, Dhatariya K, Forbes A, Puttanna guidance for the management of blood glucose in people with and with-
A, et al. Joint British Diabetes Societies for Inpatient Care (JBDS-IP) out diabetes. Diabet Med [Internet]. 2021 Jan 1 [cited 2022
Clinical Guideline Inpatient care of the frail older adult with diabetes: Aug 13];38(1). Available from: https://pubmed.ncbi.nlm.nih.gov/
an Executive Summary. Diabet Med [Internet]. 2020 Dec 1 [cited 2022 32740972/
Aug 13];37(12):1981–91. Available from: https:// 1032. Aberer F, Hochfellner DA, Sourij H, Mader JK. A Practical Guide
pubmed.ncbi.nlm.nih.gov/32533711/ for the Management of Steroid Induced Hyperglycaemia in the Hospital.
1019. Gulliford MC, Charlton J, Latinovic R. Risk of diabetes associated J Clin Med [Internet]. 2021 May 2 [cited 2022 Aug 13];10(10):10.
with prescribed glucocorticoids in a large population. Diabetes Care Available from: /pmc/articles/PMC8157052/
[Internet]. 2006 Dec [cited 2022 Aug 13];29(12):2728–9. Available from: 1033. Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman
https://www.researchgate.net/publication R, Hirsch IB, et al. American Association of Clinical Endocrinologists
/6668726_Risk_of_Diabetes_Associated_With_Prescribed_ and American Diabetes Association consensus statement on inpatient
Glucocorticoids_in_a_Large_Population glycemic control. Diabetes Care [Internet]. 2009 Jun [cited 2022
1020. Waljee AK, Rogers MAM, Lin P, Singal AG, Stein JD, Marks RM, Aug 13];32(6):1119–31. Available from: https://
et al. Short term use of oral corticosteroids and related harms among pubmed.ncbi.nlm.nih.gov/19429873/
adults in the United States: population based cohort study. BMJ 1034. Boschmann M, Michalsen A. Fasting therapy - old and new per-
[Internet]. 2017 Apr 12 [cited 2022 Aug 13];357:j1415. Available from: spectives. Forsch Komplementmed [Internet]. 2013 Dec [cited 2022
https://pubmed.ncbi.nlm.nih.gov/28404617/ Aug 11];20(6):410–1. Available from: https://pubmed.ncbi.nlm.nih.gov/
1021. Wu J, MacKie SL, Pujades-Rodriguez M. Glucocorticoid dose- 24434754/
dependent risk of type 2 diabetes in six immune-mediated inflammatory 1035. Persynaki A, Karras S, Pichard C. Unraveling the metabolic health
diseases: a population-based cohort analysis. BMJ Open Diabetes Res benefits of fasting related to religious beliefs: A narrative review.
Care [Internet]. 2020 Jul 27 [cited 2022 Aug 13];8(1). Available from: Nutrition [Internet]. 2017 Mar 1 [cited 2022 Aug 11];35:14–20.
1022. Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. 1036. Julka S, Sachan A, Bajaj S, Sahay R, Chawla R, Agrawal N, et al.
Lancet [Internet]. 2009 [cited 2022 Aug 13];373(9677):1798–807. Glycemic management during Jain fasts. Indian J Endocrinol Metab
Available from: https://pubmed.ncbi.nlm.nih.gov/19465235/ [Internet]. 2017 Jan 1 [cited 2022 Aug 11];21(1):238. Available from:
1023. Geer EB, Islam J, Buettner C. Mechanisms of Glucocorticoid- /pmc/articles/PMC5240069/
Induced Insulin Resistance: Focus on Adipose Tissue Function and 1037. Hassanein M, Al-Arouj M, Hamdy O, Bebakar WMW, Jabbar A,
Lipid Metabolism. Endocrinol Metab Clin North Am [Internet]. 2014 Al-Madani A, et al. Diabetes and Ramadan: Practical guidelines. Diabetes
Mar [cited 2022 Aug 13];43(1):75. Available from: /pmc/articles/ Res Clin Pract [Internet]. 2017 Apr 1 [cited 2022 Aug 11];126:303–16.
PMC3942672/ Available from: https://pubmed.ncbi.nlm.nih.gov/28347497/
1024. Pernicova I, Kelly S, Ajodha S, Sahdev A, Bestwick JP, Gabrovska 1038. Baruah MP, Kalra S, Unnikrishnan AG, Raza SA, Somasundaram
P, et al. Metformin to reduce metabolic complications and inflammation N, John M, et al. Management of hyperglycemia in geriatric patients with
in patients on systemic glucocorticoid therapy: a randomised, double- diabetes mellitus: South Asian consensus guidelines. Indian J Endocrinol
blind, placebo-controlled, proof-of-concept, phase 2 trial. Lancet Metab [Internet]. 2011 [cited 2022 Aug 11];15(2):75. Available from:
Di abet es Endoc ri nol [Inte rn e t ] . 20 2 0 A p r 1 [ c i t e d 2 02 2 /pmc/articles/PMC3125011/
Aug 13];8(4):278–91. Available from: https://pubmed.ncbi.nlm.nih.gov/ 1039. Gangopadhyay KK, Singh P. Consensus Statement on Dose
32109422/ Modifications of Antidiabetic Agents in Patients with Hepatic
1025. He J, Xu C, Kuang J, Liu Q, Jiang H, Mo L, et al. Impairment. Indian J Endocrinol Metab [Internet]. 2017 Mar 1 [cited
Thiazolidinediones attenuate lipolysis and ameliorate dexamethasone- 2022 Aug 11];21(2):341–54. Available from: https://
induced insulin resistance. Metabolism [Internet]. 2015 Jul 1 [cited pubmed.ncbi.nlm.nih.gov/28459036/
2022 Aug 13];64(7):826–36. Available from: https:// 1040. Betônico CCR, Titan SMO, Correa-Giannella MLC, Nery M,
pubmed.ncbi.nlm.nih.gov/25825274/ Queiroz M. Management of diabetes mellitus in individuals with chronic
1026. Gerards MC, Venema GE, Patberg KW, Kross M, Potter van Loon kidney disease: therapeutic perspectives and glycemic control. Clinics
BJ, Hageman IMG, et al. Dapagliflozin for prednisone-induced (Sao Paulo) [Internet]. 2016 Jan 1 [cited 2022 Aug 11];71(1):47–53.
hyperglycaemia in acute exacerbation of chronic obstructive pulmonary Available from: https://pubmed.ncbi.nlm.nih.gov/26872083/
disease. Diabetes Obes Metab [Internet]. 2018 May 1 [cited 2022 1041. Al-Arouj M, Assaad-Khalil S, Buse J, Fahdil I, Fahmy M, Hafez S,
Aug 13];20(5):1306–10. Available from: https:// et al. Recommendations for Management of Diabetes During Ramadan:
pubmed.ncbi.nlm.nih.gov/29316157/ Update 2010. Diabetes Care [Internet]. 2010 Aug [cited 2022
1027. Ito S, Ogishima H, Kondo Y, Sugihara M, Hayashi T, Chino Y, Aug 11];33(8):1895. Available from: /pmc/articles/PMC2909082/
et al. Early diagnosis and treatment of steroid-induced diabetes mellitus in 1042. Bashir M, Pathan MF, Raza S, Ahmad J, Azad Khan A, Ishtiaq O,
patients with rheumatoid arthritis and other connective tissue diseases. et al. Role of oral hypoglycemic agents in the management of type 2
Mod Rheumatol [Internet]. 2014 [cited 2022 Aug 13];24(1):52–9. diabetes mellitus during Ramadan. Indian J Endocrinol Metab
Available from: https://pubmed.ncbi.nlm.nih.gov/24261759/ [Internet]. 2012 [cited 2022 Aug 11];16(4):503. Available from: https://
1028. Wallace MD, Metzger NL. Optimizing the Treatment of Steroid- pubmed.ncbi.nlm.nih.gov/22837904/
Induced Hyperglycemia. Ann Pharmacother [Internet]. 2018 Jan 1 [cited 1043. Sarita Bajaj. Newer antidiabetic drugs in Ramadan. J Pak Med
2022 Aug 13];52(1):86–90. Available from: https:// Assoc . 2015 May;65(5 Suppl 1):S40-43.
pubmed.ncbi.nlm.nih.gov/28836444/ 1044. Hassanein M, Al-Arouj M, Hamdy O, Bebakar WMW, Jabbar A,
1029. HE TP, DL QF, R RG, JG GG, AL TP. Steroid hyperglycemia: Al-Madani A, et al. Diabetes and Ramadan: Practical guidelines. Diabetes
Prevalence, early detection and therapeutic recommendations: A narrative Res Clin Pract [Internet]. 2017 Apr 1 [cited 2022 Aug 11];126:303–16.
review. World J Diabetes [Internet]. 2015 [cited 2022 Aug 13];6(8):1073. Available from: https://pubmed.ncbi.nlm.nih.gov/28347497/
Available from: https://pubmed.ncbi.nlm.nih.gov/26240704/ 1045. Diabetes and Ramadan: Practical Guidelines. International
1030. Clore JN, Thurby-Hay L. Glucocorticoid-induced hyperglycemia. Diabetes Federation; 2016. Available from: https://www.idf.org/e-li-
Endocr Pract [Internet]. 2009 Jul [cited 2022 Aug 13];15(5):469–74. brary/ guidelines/87-diabetes-and-ramadan-practical-25. [Last accessed
Available from: https://pubmed.ncbi.nlm.nih.gov/19454391/ on 2016 Jun 19]. - Google Search [Internet]. [cited 2022 Aug 11].
1031. Rayman G, Lumb AN, Kennon B, Cottrell C, Nagi D, Page E, et al. Available from: https://www.google.com/search?q=Diabetes+and+
Dexamethasone therapy in COVID-19 patients: implications and Ramadan%3A+Practical+Guidelines.+International+Diabetes+
Federation%3B+2016.+Available+from%3A+ Ramadan (DAR) International Alliance [Internet]. Available from:

https%3A%2F%2Ffanyv88.com%3A443%2Fhttps%2Fwww.idf.org%2Fe-library%2F+guidelines%2F87- www.idf.org/guidelines/diabetes-in-ramadan
diabetes-and-ramadan-practical-25.+%5BLast+accessed+on+2016+ 1059. Buchmann M, Wermeling M, Lucius-Hoene G, Himmel W.
J u n + 1 9 % 5 D . & e i = N p z 0 Y r P L L 9 K y 4 - Experiences of food abstinence in patients with type 2 diabetes: a quali-
EPrYanWA&ved=0ahUKEwizvoulj775AhVS2TgGHS3DCQsQ4dUD- tative study. BMJ Open [Internet]. 2016 [cited 2022 Aug 11];6(1).
CA4&uact=5&oq=Diabetes+and+Ramadan%3A+Practical+ Available from: https://pubmed.ncbi.nlm.nih.gov/26739724/
Guidelines.+International+Diabetes+Federation%3B+2016.+Available+ 1060. Ali S, Davies MJ, Brady EM, Gray LJ, Khunti K, Beshyah SA,
from%3A+https%3A%2F%2Ffanyv88.com%3A443%2Fhttps%2Fwww.idf.org%2Fe-library%2F+ et al. Guidelines for managing diabetes in Ramadan. Diabet Med
guidelines%2F87-diabetes-and-ramadan-practical-25.+%5BLast+ [Internet]. 2016 Oct 1 [cited 2022 Aug 11];33(10):1315–29. Available
a c c e s s e d + o n + 2 0 1 6 + J u n + from: https://pubmed.ncbi.nlm.nih.gov/26802436/
19%5D.&gs_lcp=Cgdnd3Mtd2l6EAMyBwgAEEcQsAMyBwgAEEc- 1061. Almalki MH, Alshahrani F. Options for Controlling Type 2
QsAMyBwgAEEcQsAMyBwgAEEcQsAMyBwgAEEcQsAMyBwgA- Diabetes during Ramadan. Front Endocrinol (Lausanne) [Internet].
EEcQsAMyBwgAEEcQsAMyBwgAEEcQsANKBAhBGABKBAhG- 2016 Apr 18 [cited 2022 Aug 11];7(APR). Available from: https://
GABQAFgAYJDeBWgEcAF4AIABAIgBAJIBAJgBAMgBCMABA- pubmed.ncbi.nlm.nih.gov/27148163/
Q&sclient=gws-wiz 1062. Niazi AK, Kalra S. Patient centred care in diabetology: an Islamic
1046. Kalra S, Bajaj S, Gupta Y, Agarwal P, Singh S, Julka S, et al. Fasts, perspective from South Asia. J Diabetes Metab Disord [Internet]. 2012
feasts and festivals in diabetes-1: Glycemic management during Hindu Dec 29 [cited 2022 Aug 11];11(1):30. Available from: /pmc/articles/
fasts. Indian J Endocrinol Metab [Internet]. 2015 Mar 1 [cited 2022 PMC3598159/
Aug 11];19(2):198. Available from: /pmc/articles/PMC4319259/ 1063. Kalra S, Aamir AH, Raza A, Das AK, Khan AKA, Shrestha D,
1047. Latt T SK. Managing diabetes during fasting-A focus on Buddhist et al. Place of sulfonylureas in the management of type 2 diabetes mellitus
Lent. Diabetes Voice. 2012;57:42–5. in South Asia: A consensus statement. Indian J Endocrinol Metab
1048. Zainudin SB, Ang DY, Soh AWE. Knowledge of diabetes mellitus [Internet]. 2015 Sep 1 [cited 2022 Aug 11];19(5):577–96. Available
and safe practices during Ramadan fasting among Muslim patients with from: https://pubmed.ncbi.nlm.nih.gov/26425465/
diabetes mellitus in Singapore. Singapore Med J [Internet]. 2017 May 1 1064. Zargar AH, Siraj M, Jawa AA, Hasan M, Mahtab H. Maintenance
[cited 2022 Aug 11];58(5):246. Available from: /pmc/articles/ of glycaemic control with the evening administration of a long acting
PMC5435842/ sulphonylurea in male type 2 diabetic patients undertaking the
1049. Norouzy A, Mohajeri SMR, Shakeri S, Yari F, Sabery M, Ramadan fast. Int J Clin Pract [Internet]. 2010 Jul [cited 2022
Philippou E, et al. Effect of Ramadan fasting on glycemic control in Aug 11];64(8):1090–4. Available from: https://
patients with Type 2 diabetes. J Endocrinol Invest [Internet]. 2012 [cited pubmed.ncbi.nlm.nih.gov/20455956/
2022 Aug 11];35(8):766–71. Available from: https:// 1065. Rashid F, Abdelgadir E. A systematic review on efficacy and safety
pubmed.ncbi.nlm.nih.gov/21986487/ of the current hypoglycemic agents in patients with diabetes during
1050. Kovil R, Shaikh N. Study of Beneficial Impact on Specific Ramadan fasting. Diabetes Metab Syndr [Internet]. 2019 Mar 1 [cited
Biomarkers in Type 2 Diabetes During Ramadan Fasting 2022 Aug 12];13(2):1413–29. Available from: https://
(Unintentional Intermittent Fasting). J Assoc Physicians India. 2020 pubmed.ncbi.nlm.nih.gov/31336501/
Jun;68(6):26–9. 1066. Gray LJ, Dales J, Brady EM, Khunti K, Hanif W, Davies MJ.
1051. Abdeali M, Dashti S, Ahmedani MY. Effect of Ramadan fasting on Safety and effectiveness of non-insulin glucose-lowering agents in the
the weight of person with diabetes. Int J Clin Pract. 2020;74(3):e13452. treatment of people with type 2 diabetes who observe Ramadan: a sys-
1052. Almansour HA, Chaar B, Saini B. Fasting, Diabetes, and tematic review and meta-analysis. Diabetes Obes Metab [Internet]. 2015
Optimizing Health Outcomes for Ramadan Observers: A Literature Jul 1 [cited 2022 Aug 11];17(7):639–48. Available from: https://
Review. Diabetes Ther [Internet]. 2017 Apr 1 [cited 2022 pubmed.ncbi.nlm.nih.gov/25777247/
Aug 11];8(2):227–49. Available from: https://pubmed.ncbi.nlm.nih.gov/ 1067. Saboo B, Joshi S, Shah SN, Tiwaskar M, Vishwanathan V,
28181087/ Bhandari S, et al. Management of Diabetes during Fasting and Feasting
1053. Bravis V, Hui E, Salih S, Mehar S, Hassanein M, Devendra D. in India. J Assoc Physicians India. 2019 Sep;67(9):70–7.
Ramadan Education and Awareness in Diabetes (READ) programme for 1068. Hassanein M, Abdallah K, Schweizer A. A double-blind, random-
Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med ized trial, including frequent patient-physician contacts and Ramadan-
[Internet]. 2010 [cited 2022 Aug 11];27(3):327–31. Available from: focused advice, assessing vildagliptin and gliclazide in patients with type
https://pubmed.ncbi.nlm.nih.gov/20536496/ 2 diabetes fasting during Ramadan: the STEADFAST study. Vasc Health
1054. Dabral S, Mukherjee S, Saha N, Manjavkar S, Kohli S. A survey of Risk Manag [Internet]. 2014 [cited 2022 Aug 11];10:319–26. Available
fasting practices and acceptance of an intervention for achieving control from: https://pubmed.ncbi.nlm.nih.gov/24920915/
in diabetes during Ramadan. Natl Med J India [Internet]. 2020 Jan 1 1069. Aravind SR, Ismail SB, Balamurugan R, Gupta JB, Wadhwa T,
[cited 2022 Aug 12];33(1):5. Available from: https://nmji.in/a-survey- Loh SM, et al. Hypoglycemia in patients with type 2 diabetes from India
of-fasting-practices-and-acceptance-of-an-intervention-for-achieving- and Malaysia treated with sitagliptin or a sulfonylurea during Ramadan: a
control-in-diabetes-during-ramadan/ randomized, pragmatic study. Curr Med Res Opin [Internet]. 2012 Aug
1055. Abdul Jabbar. Glucose monitoring during Ramadan. J Pak Med [cited 2022 Aug 11];28(8):1289–96. Available from: https://
Assoc . 2015 May;65((5 Suppl 1)):S51-53. pubmed.ncbi.nlm.nih.gov/22738801/
1056. McEwen LN, Ibrahim M, Ali NM, Assaad-Khalil SH, Tantawi HR, 1070. Brady EM, Davies MJ, Gray LJ, Saeed MA, Smith D, Hanif W,
Nasr G, et al. Impact of an individualized type 2 diabetes education et al. A randomized controlled trial comparing the GLP-1 receptor agonist
program on clinical outcomes during Ramadan. BMJ Open Diabetes liraglutide to a sulphonylurea as add on to metformin in patients with
Res Care [Internet]. 2015 Mar 10 [cited 2022 Aug 11];3(1). Available established type 2 diabetes during Ramadan: the Treat 4 Ramadan
from: https://pubmed.ncbi.nlm.nih.gov/26113984/ Trial. Diabetes Obes Metab [Internet]. 2014 [cited 2022
1057. Hanif W, Patel V, Ali SN, Karamat A, Saeed M, Hassanein M, Aug 11];16(6):527–36. Available from: https://
et al. The South Asian Health Foundation (UK) guidelines for managing pubmed.ncbi.nlm.nih.gov/24373063/
diabetes during Ramadan. Diabetes Res Clin Pract. 2020 1071. Azar ST, Echtay A, Wan Bebakar WM, al Araj S, Berrah A, Omar
Jun;164:108145. M, et al. Efficacy and safety of liraglutide compared to sulphonylurea
1058. Diabetes and Ramadan Diabetes and Ramadan International during Ramadan in patients with type 2 diabetes (LIRA-Ramadan): a
Diabetes Federation (IDF), in collaboration with the Diabetes and randomized trial. Diabetes Obes Metab [Internet]. 2016 Oct 1 [cited
2022 Aug 11];18(10):1025–33. Available from: https:// not to attend: a systematic review. Diabet Med [Internet]. 2017 Jan 1
pubmed.ncbi.nlm.nih.gov/27376711/ [cited 2022 Aug 12];34(1):14–26. Available from: https://
1072. Wan Seman WJ, Kori N, Rajoo S, Othman H, Mohd Noor N, pubmed.ncbi.nlm.nih.gov/26996982/
Wahab NA, et al. Switching from sulphonylurea to a sodium-glucose 1086. Mulcahy K, Maryniuk M, Peeples M, Peyrot M, Tomky D, Weaver
cotransporter2 inhibitor in the fasting month of Ramadan is associated T, et al. Diabetes self-management education core outcomes measures.
with a reduction in hypoglycaemia. Diabetes Obes Metab [Internet]. 2016 Diabetes Educ [Internet]. 2003 [cited 2022 Aug 12];29(5):768–803.
[cited 2022 Aug 11];18(6):628–32. Available from: https:// Available from: https://pubmed.ncbi.nlm.nih.gov/14603868/
pubmed.ncbi.nlm.nih.gov/26889911/ 1087. Management of Hyperglycemia in Type 2 Diabetes: ADA-EASD
1073. Beshyah SA, Chatterjee S, Davies MJ. Use of SGLT2 inhibitors Consensus Report 2022 | American Diabetes Association [Internet]. [cit-
during Ramadan: a survey of physicians’ views and practical guidance. ed 2022 Sep 1]. Available from: https://professional.diabetes.org/content-
British Journal of Diabetes [Internet]. 2016 Mar 8 [cited 2022 page/management-hyperglycemia-type-2-diabetes-ada-easd-consensus-
Aug 11];16(1):20–4. Available from: https://www.bjd-abcd.com/ report-2022
index.php/bjd/article/view/121/252 1088. Deepa M, Bhansali A, Anjana R, Pradeepa R, Joshi S, Joshi P, et al.
1074. Kalra S, Jawad F. Insulin in Ramadan. J Pak Med Assoc. Knowledge and awareness of diabetes in urban and rural India: The
2015;65:S44-46. Indian Council of Medical Research India Diabetes Study (Phase I):
1075. Saboo B, Joshi S, Shah SN, Tiwaskar M, Vishwanathan V, Indian Council of Medical Research India Diabetes 4. Indian J
Bhandari S, et al. Management of Diabetes during Fasting and Feasting Endocrinol Metab [Internet]. 2014 May 1 [cited 2022
in India. Vol. 67, Journal of The Association of Physicians of India ■. Aug 12];18(3):379. Available from: /pmc/articles/PMC4056139/
2019. 1089. Mohan D, Raj D, Shanthirani C S, Datta M, Unwin N C, Kapur A,
1076. Hassanein M, Echtay AS, Malek R, Omar M, Shaikh SS, Ekelund et al. Awareness and knowledge of diabetes in Chennai–the Chennai
M, et al. Original paper: Efficacy and safety analysis of insulin degludec/ Urban Rural Epidemiology Study [CURES-9]. J Assoc Physicians
insulin aspart compared with biphasic insulin aspart 30: A phase 3, mul- India. 2005 Apr;53:283–7.
ticentre, international, open-label, randomised, treat-to-target trial in pa- 1090. Ramachandran A, Snehalatha C, Baskar ADS, Mary S, Sathish
tients with type 2 diabetes fasting during Ramadan. Diabetes Res Clin Kumar CK, Selvam S, et al. Temporal changes in prevalence of diabetes
Pract. 2018 Jan;135:218–26. and impaired glucose tolerance associated with lifestyle transition occur-
1077. Pathan F, Latif ZA, Sahay RK, Zargar AH, Raza SA, Khan AKA, ring in the rural population in India. Diabetologia [Internet]. 2004 May
et al. Update to South Asian consensus guideline: Use of newer insulins [cited 2022 Aug 12];47(5):860–5. Available from: https://
in diabetes during Ramadan Revised Guidelines on the use of insulin in pubmed.ncbi.nlm.nih.gov/15114469/
Ramadan. J Pak Med Assoc. 2016;66(6):777–8. 1091. Singh DK, Tari V. Structured diabetes care (Freedom 365*) pro-
1078. Alawadi F, Alsaeed M, Bachet F, Bashier A, Abdulla K, vides better glycemic control than routine medical care in type 2 diabetes:
Abuelkheir S, et al. Impact of provision of optimum diabetes care on proof of concept observational study. Int J Diabetes Dev Ctries. 2015 Sep
the safety of fasting in Ramadan in adult and adolescent patients with 1;35(3):289–96.
type 1 diabetes mellitus. Diabetes Res Clin Pract [Internet]. 2020 Nov 1 1092. Jankowska-Polańska B, Fal AM, Uchmanowicz I, Seń M, Polański
[cited 2022 Aug 12];169. Available from: https:// J, Kurpas D. Influence of organized diabetic education on self-control and
pubmed.ncbi.nlm.nih.gov/32971155/ quality of life of patients with type 2 diabetes. Int J Diabetes Dev Ctries.
1079. Deeb A, Elbarbary N, Smart CE, Beshyah SA, Habeb A, Kalra S, 2015 Sep 1;35:79–87.
et al. ISPAD Clinical Practice Consensus Guidelines: Fasting during 1093. Chawla SS, Kaur S, Bharti A, Garg R, Kaur M, Soin D, et al.
Ramadan by young people with diabetes. Pediatr Diabetes [Internet]. Impact of health education on knowledge, attitude, practices and glyce-
2020 Feb 1 [cited 2022 Aug 12];21(1):5–17. Available from: https:// mic control in type 2 diabetes mellitus. J Family Med Prim Care
pubmed.ncbi.nlm.nih.gov/31659852/ [Internet]. 2019 [cited 2022 Aug 12];8(1):261. Available from: https://
1080. Turner R. Intensive blood-glucose control with sulphonylureas or pubmed.ncbi.nlm.nih.gov/30911517/
insulin compared with conventional treatment and risk of complications 1094. Verma R, Khanna P, Bharti. National programme on prevention
in patients with type 2 diabetes (UKPDS 33). The Lancet [Internet]. 1998 and control of diabetes in India: Need to focus. Australas Med J [Internet].
Sep 12 [cited 2022 Aug 12];352(9131):837–53. Available from: http:// 2012 [cited 2022 Aug 12];5(6):310. Available from: /pmc/articles/
www.thelancet.com/article/S0140673698070196/fulltext PMC3395295/
1081. Chrvala CA, Sherr D, Lipman RD. Diabetes self-management ed- 1095. Balagopal P, Kamalamma N, Patel TG, Misra R. A community-
ucation for adults with type 2 diabetes mellitus: A systematic review of based diabetes prevention and management education program in a rural
the effect on glycemic control. Patient Educ Couns [Internet]. 2016 Jun 1 village in India. Diabetes Care [Internet]. 2008 Jun [cited 2022
[cited 2022 Aug 12];99(6):926–43. Available from: https:// Aug 12];31(6):1097–104. Available from: https://
1082. Scain SF, Friedman R, Gross JL. A structured educational program 1096. Majra JP, Verma R. Opportunistic screening for random blood
improves metabolic control in patients with type 2 diabetes: a randomized glucose level among adults attending a rural tertiary care centre in
controlled trial. Diabetes Educ [Internet]. 2009 Jul [cited 2022 Haryana during world health day observation activity. Int J Community
Aug 12];35(4):603–11. Available from: https:// Med Pu blic Health [Internet]. 2017 May 2 2 [cited 2022
pubmed.ncbi.nlm.nih.gov/19451553/ Aug 12];4(6):1951–6. Available from: https://www.ijcmph.com/
1083. Norris SL, Lau J, Smith SJ, Schmid CH, Engelgau MM. Self- index.php/ijcmph/article/view/1272
management education for adults with type 2 diabetes: a meta-analysis 1097. Nathan DM, Balkau B, Bonora E, Borch-Johnsen K, Buse JB,
of the effect on glycemic control. Diabetes Care [Internet]. 2002 Jul [cited Colagiuri S, et al. International Expert Committee Report on the Role
2022 Aug 12];25(7):1159–71. Available from: https:// of the A1C Assay in the Diagnosis of Diabetes. Diabetes Care
pubmed.ncbi.nlm.nih.gov/12087014/ [Internet]. 2009 Jul [cited 2022 Aug 12];32(7):1327. Available from:
1084. Shrivastava SRBL, Shrivastava PS, Ramasamy J. Role of self-care /pmc/articles/PMC2699715/
in management of diabetes mellitus. J Diabetes Metab Disord [Internet]. 1098. Saboo B, Parikh RM. RSSDI’s Defeat Diabetes Campaign: India
2013 Mar 5 [cited 2022 Aug 12];12(1):1. Available from: /pmc/articles/ takes a major leap in the direction of diabetes care capital of the world. Int
PMC3599009/ J Diabetes Dev Ctries. 2021 Oct;41(4):523–5.
1085. Horigan G, Davies M, Findlay-White F, Chaney D, Coates V. 1099. Unnikrishnan R, Anjana RM, Deepa M, Pradeepa R, Joshi SR,
Reasons why patients referred to diabetes education programmes choose Bhansali A, et al. Glycemic control among individuals with self-
reported diabetes in India–the ICMR-INDIAB Study. Diabetes Technol 1112. Bansal C, Kaushik R, Mohan Kaushik R. Awareness of diabetic
Ther [Internet]. 2014 Sep 1 [cited 2022 Aug 12];16(9):596–603. nephropathy in patients with type 2 diabetes mellitus: the Indian scenario.
Available from: https://pubmed.ncbi.nlm.nih.gov/25101698/ J Nephropharmacol. 2018 May 20;7(2):90–7.
1100. Hussain R, Rajesh B, Giridhar A, Gopalakrishnan M, Sadasivan S, 1113. Siaw MYL, Ko Y, Malone DC, Tsou KYK, Lew YJ, Foo D, et al.
James J, et al. Knowledge and awareness about diabetes mellitus and Impact of pharmacist-involved collaborative care on the clinical, human-
diabetic retinopathy in suburban population of a South Indian state and istic and cost outcomes of high-risk patients with type 2 diabetes
its practice among the patients with diabetes mellitus: A population-based (IMPACT): a randomized controlled trial. J Clin Pharm Ther [Internet].
study. Indian J Ophthalmol [Internet]. 2016 Apr 1 [cited 2022 2017 Aug 1 [cited 2022 Aug 12];42(4):475–82. Available from: https://
Aug 12];64(4):272–6. Available from: https://pubmed.ncbi.nlm.nih.gov/ pubmed.ncbi.nlm.nih.gov/28449205/
27221678/ 1114. Ventola CL. Social media and health care professionals: benefits,
1101. Devi R, Kapoor B, Singh M. Effectiveness of self-learning module risks, and best practices. P T. 2014 Jul;39(7):491–520.
on the knowledge and practices regarding foot care among type II diabe- 1115. Gabarron E, Årsand E, Wynn R. Social Media Use in Interventions
tes patients in East Delhi, India. Int J Community Med Public Health. for Diabetes: Rapid Evidence-Based Review. J Med Internet Res.
2016;2133–41. 2018;20(8):e10303.
1102. Patel N, Deshpande S, Godbole V, Champaneri V, Singh N. 1116. Elnaggar A, Ta Park V, Lee SJ, Bender M, Siegmund LA, Park LG.
Awareness and approach towards diagnosis and treatment of diabetes Patients’ Use of Social Media for Diabetes Self-Care: Systematic Review.
type 2 and its complication among general practioners of western J Med Internet Res. 2020;22(4):e14209.
Vadodara. Int J Diabetes Dev Ctries [Internet]. 2015 Sep 1 [cited 2022 1117. Thomas RL, Alabraba V, Barnard S, Beba H, Brake J, Cox A, et al.
Aug 12];3(35):138–42. Available from: https://www.infona.pl//resource/ Use of Social Media as a Platform for Education and Support for People
bwmeta1.element.springer-doi-10_1007-S13410-014-0192-0 With Diabetes During a Global Pandemic. J Diabetes Sci Technol. 2021
1103. Kide S, Rangari A, Shiral R, Mane N, Yadav P, Ambulkar K, et al. Oct 31;193229682110548.
Knowledge and awareness of diabetes amongst diabetes patients in 1118. Shrivastava SRBL, Shrivastava PS, Ramasamy J. Role of self-care
Wardha region. International Journal of Diabetes in Developing in management of diabetes mellitus. J Diabetes Metab Disord [Internet].
Countries 2014 34:4 [Internet]. 2014 Jan 30 [cited 2022 2013 Mar 5 [cited 2022 Aug 12];12(1). Available from: /pmc/articles/
Aug 12];34(4):232–232. Available from: https://link.springer.com/arti- PMC3599009/
cle/10.1007/s13410-013-0178-3 1119. Krishnan A, Gupta V, Ritvik, Nongkynrih B, Thakur JS. How to
1104. Limaye TY, Wagle SS, Kumaran K, Joglekar C v., Nanivadekar A, Effectively Monitor and Evaluate NCD Programmes in India. Indian J
Yajnik CS. Lack of knowledge about diabetes in Pune—the city of Community Med [Internet]. 2011 Dec 1 [cited 2022
knowledge! Int J Diabetes Dev Ctries. 2016 Sep 1;36(3):263–70. Aug 12];36(Suppl1):S57. Available from: /pmc/articles/PMC3354904/
1105. Long P, Long KNG, Kedia A, Gren LH, Smith A, Biswas J. A 1120. Mahajan PB. Role of medical colleges in prevention and control of
cross-sectional study of diabetic knowledge in West Bengal, India: an diabetes in India: a ten point approach. International Journal of Diabetes
analysis based on access to health care. Int J Diabetes Dev Ctries in Developing Countries 2011 31:1 [Internet]. 2011 Jan 22 [cited 2022
[Internet]. 2015 Nov 1 [cited 2022 Aug 12];4(35):614–9. Available from: Aug 12];31(1):41–2. Available from: https://link.springer.com/article/
https://www.infona.pl//resource/bwmeta1.element.springer-doi- 10.1007/s13410-010-0003-1
10_1007-S13410-015-0293-4 1121. Venkataraman K, Kannan A, Viswanathan M. Challenges in dia-
1106. Mathew A, Jacob N, Jose S, P R, K S, R S, et al. Knowledge about betes management with particular reference to India. Int J Diabetes Dev
risk factors, symptoms and complications of diabetes among adults in Ctries [Internet]. 2009 [cited 2022 Aug 12];29(3):103–9. Available from:
South India. Int J Med Sci Public Health. 2014;3(9):1086. https://pubmed.ncbi.nlm.nih.gov/20165646/
1107. Muninarayana C, Balachandra G, Hiremath S, Iyengar K, Anil N. 1122. Basu S, Sharma N. Diabetes self-care in primary health facilities in
Prevalence and awareness regarding diabetes mellitus in rural Tamaka, India - challenges and the way forward. World J Diabetes [Internet]. 2019
Kolar. Int J Diabetes Dev Ctries [Internet]. 2010 Jan 1 [cited 2022 Jun 6 [cited 2022 Aug 12];10(6):341. Available from: /pmc/articles/
Aug 12];30(1):18–21. Available from: https://pubmed.ncbi.nlm.nih.gov/ PMC6571487/
20431801/ 1123. Gupta K, Gupta S. Barriers to insulin therapy. J Diabetes Educ.
1108. Saurabh S, Sarkar S, Selvaraj K, Kar S, Kumar S, Roy G. 2013;3:17–23.
Effectiveness of foot care education among people with type 2 diabetes 1124. Bhojani U, Kolsteren P, Criel B, Henauw S de, Beerenahally TS,
in rural Puducherry, India. Indian J Endocrinol Metab [Internet]. 2014 Verstraeten R, et al. Intervening in the local health system to improve
Jan 1 [cited 2022 Aug 12];18(1):106–10. Available from: https:// diabetes care: lessons from a health service experiment in a poor urban
pubmed.ncbi.nlm.nih.gov/24701439/ neighborhood in India. Glob Health Action [Internet]. 2015 [cited 2022
1109. Singh A, Mani K, Krishnan A, Aggarwal P, Gupta S. Prevalence, Aug 12];8(1). Available from: /pmc/articles/PMC4649018/
awareness, treatment and control of diabetes among elderly persons in an 1125. Basu S, Garg S. The barriers and challenges toward addressing the
urban slum of delhi. Indian J Community Med [Internet]. 2012 Oct [cited social and cultural factors influencing diabetes self-management in Indian
2022 Aug 12];37(4):236–9. Available from: https:// populations. Journal of Social Health and Diabetes. 2017
pubmed.ncbi.nlm.nih.gov/23293438/ Dec;05(02):071–6.
1110. Jaiswal K, Moghe N, Mc M, Khaladkar K, Vaishnao L. 1126. Babu MS, Gowdappa HB, Kalpana T, Vidyalaxmi K, Nikhil B,
Knowledge, attitude & practices of type II diabetes mellitus patients in Chakravarthy T. Knowledge, Attitude and Practices of Diabetic Patients -
a tertiary care teaching institute of central India. J Diabetes Metab Disord A Cross Sectional Study in a Tertiary Care Hospital in Mysore. J Assoc
Control [Internet]. 2019 Jan 10 [cited 2022 Aug 12];Volume 6(Issue Physicians India . 2015 Aug;63(8):96.
1):1–4. Available from: https://medcraveonline.com/JDMDC/JDMDC- 1127. Chandalia HB, Modi S. Counseling strategies (Dr. Vinod
06-00172.php Dhurandhar Oration at AIAAROCON-Pune on 9th February, 2013). . J
1111. Sharma S, Jha J, Varshney A, Chauhan L. Awareness of various Obes Metab Res. 2014;1:43.
aspects of diabetes among people visiting tertiary eye care institute in 1128. Hasan H, Zodpey S, Saraf A. Diabetes care in India: Assessing the
north India. Clin Epidemiol Glob Health [Internet]. 2020 Mar 1 [cited need for Evidence-Based education. . South-East Asian J Med Educ .
2022 Aug 12];8(1):96–100. Available from: http://cegh.net/article/ 2011;5:15–8.
S2213398418302148/fulltext 1129. Madhu S, Lalitha K. Education needs of Diabetic Patients with
Low Socio-Economic and Literacy Levels, 15th International Diabetes
Federation (IDF) Congress. Kobe, Japan. Scientific Supplement. 1144. Bonsignore M, Barkow K, Jessen F, Heun R. Validity of the five-
1994;37. item WHO Well-Being Index (WHO-5) in an elderly population. Eur
1130. Dickinson JK, Guzman SJ, Maryniuk MD, O’Brian CA, Kadohiro Arch Psychiatry Clin Neurosci [Internet]. 2001 [cited 2022
JK, Jackson RA, et al. The Use of Language in Diabetes Care and Aug 13];251 Suppl 2(SUPPL. 2):27–31. Available from: https://
Education. Diabetes Care [Internet]. 2017 Dec 1 [cited 2022 Sep pubmed.ncbi.nlm.nih.gov/11824831/
1];40(12):1790–9. Available from: https://pubmed.ncbi.nlm.nih.gov/ 1145. Kalra S, Sridhar GR, Balhara YPS, Sahay RK, Bantwal G, Baruah
29042412/ MP, et al. National recommendations: Psychosocial management of dia-
1131. Ciechanowski PS, Katon WJ, Russo JE. Depression and diabetes: betes in India. Indian J Endocrinol Metab [Internet]. 2013 [cited 2022
impact of depressive symptoms on adherence, function, and costs. Arch Aug 13];17(3):376. Available from: /pmc/articles/PMC3712367/
Intern Med [Internet]. 2000 Nov 27 [cited 2022 Aug 13];160(21):3278– 1146. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The preva-
85. Available from: https://pubmed.ncbi.nlm.nih.gov/11088090/ lence of comorbid depression in adults with diabetes: a meta-analysis.
1132. Kalra S, Jena BN, Yeravdekar R. Emotional and Psychological Diabetes Care [Internet]. 2001 [cited 2022 Aug 13];24(6):1069–78.
Needs of People with Diabetes. Indian J Endocrinol Metab [Internet]. Available from: https://pubmed.ncbi.nlm.nih.gov/11375373/
2018 Sep 1 [cited 2022 Aug 13];22(5):696. Available from: /pmc/arti- 1147. Mezuk B, Eaton WW, Albrecht S, Golden SH. Depression and
cles/PMC6166557/ type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care
1133. Pouwer F, Beekman ATF, Nijpels G, Dekker JM, Snoek FJ, [Internet]. 2008 Dec [cited 2022 Aug 13];31(12):2383–90. Available
Kostense PJ, et al. Rates and risks for co-morbid depression in patients from: https://pubmed.ncbi.nlm.nih.gov/19033418/
with Type 2 diabetes mellitus: results from a community-based study. 1148. Young-Hyman DL, Davis CL. Disordered Eating Behavior in
Diabetologia [Internet]. 2003 Jul 1 [cited 2022 Aug 13];46(7):892–8. Individuals With Diabetes: Importance of context, evaluation, and clas-
Available from: https://pubmed.ncbi.nlm.nih.gov/12819896/ sification. Diabetes Care [Internet]. 2010 Mar [cited 2022
1134. Schram M, Baan C, Pouwer F. Depression and quality of life in Aug 13];33(3):683. Available from: /pmc/articles/PMC2827531/
patients with diabetes: a systematic review from the European depression 1149. Khaledi M, Haghighatdoost F, Feizi A, Aminorroaya A. The prev-
in diabetes (EDID) research consortium. Curr Diabetes Rev [Internet]. alence of comorbid depression in patients with type 2 diabetes: an up-
2009 Apr 30 [cited 2022 Aug 13];5(2):112–9. Available from: https:// dated systematic review and meta-analysis on huge number of observa-
pubmed.ncbi.nlm.nih.gov/19442096/ tional studies. Acta Diabetol [Internet]. 2019 [cited 2022 Aug 13];56(6).
1135. Madhu K. Psychological and psychiatric aspects of diabetes. Available from: https://pubmed.ncbi.nlm.nih.gov/30903433/
International Journal of Diabetes in Developing Countries 2015 35:2 1150. Egede LE, Zheng D, Simpson K. Comorbid depression is associ-
[Internet]. 2015 Oct 9 [cited 2022 Aug 13];35(2):73–4. Available from: ated with increased health care use and expenditures in individuals with
https://link.springer.com/article/10.1007/s13410-015-0447-4 diabetes. Diabetes Care [Internet]. 2002 Mar [cited 2022
1136. Petrak F, Herpertz S, Albus C, Hirsch A, Kulzer B, Kruse J. Aug 13];25(3):464–70. Available from: https://
Psychosocial factors and diabetes mellitus: evidence-based treatment pubmed.ncbi.nlm.nih.gov/11874931/
guidelines. Curr Diabetes Rev [Internet]. 2005 Oct 27 [cited 2022 1151. Lin EHB, Katon W, von Korff M, Rutter C, Simon GE, Oliver M,
Aug 13];1(3):255–70. Available from: https://pubmed.ncbi.nlm.nih.gov/ et al. Relationship of depression and diabetes self-care, medication ad-
18220602/ herence, and preventive care. Diabetes Care [Internet]. 2004 Sep [cited
1137. Sridhar GR, Madhu K. Psychosocial and cultural issues in diabetes 2022 Aug 13];27(9):2154–60. Available from: https://
mellitus. Curr Sci [Internet]. 2002;83(12):1556–64. Available from: pubmed.ncbi.nlm.nih.gov/15333477/
http://www.jstor.org/stable/24108181 1152. Fisher L, Hessler D, Glasgow RE, Arean PA, Masharani U,
1138. Kalra S, Balhara YPS, Bathla M. Euthymia in Diabetes. Eur Naranjo D, et al. REDEEM: a pragmatic trial to reduce diabetes distress.
Endocrinol [Internet]. 2018 Sep 1 [cited 2022 Aug 13];14(2):18. Diabetes Care [Internet]. 2013 Sep [cited 2022 Aug 13];36(9):2551–8.
Available from: /pmc/articles/PMC6182925/ Available from: https://pubmed.ncbi.nlm.nih.gov/23735726/
1139. Kalra S, Das AK, Baruah MP, Unnikrishnan AG, Dasgupta A, 1153. Huang Y, Wei X, Wu T, Chen R, Guo A. Collaborative care for
Shah P, et al. Euthymia in Diabetes: Clinical Evidence and Practice- patients with depression and diabetes mellitus: a systematic review and
Based Opinion from an International Expert Group. Diabetes Ther meta-analysis. BMC Psychiatry [Internet]. 2013 Oct 14 [cited 2022
[Internet]. 2019 Jun 1 [cited 2022 Aug 13];10(3):791–804. Available Aug 13];13. Available from: https://pubmed.ncbi.nlm.nih.gov/
from: https://pubmed.ncbi.nlm.nih.gov/31012081/ 24125027/
1140. Association AD. 5. Lifestyle Management: Standards of Medical 1154. Lustman PJ, Griffith LS, Freedland KE, Kissel SS, Clouse RE.
Care in Diabetes—2019. Diabetes Care [Internet]. 2019 Jan 1 [cited 2022 Cognitive behavior therapy for depression in type 2 diabetes mellitus. A
Aug 13];42(Supplement_1):S46–60. Available from: https:// randomized, controlled trial. Ann Intern Med [Internet]. 1998 Oct 15
diabetesjournals.org/care/article/42/Supplement_1/S46/31274/5- [cited 2022 Aug 13];129(8):613–21. Available from: https://
Lifestyle-Management-Standards-of-Medical-Care pubmed.ncbi.nlm.nih.gov/9786808/
1141. Peyrot M, Rubin RR, Lauritzen T, Snoek FJ, Matthews DR, 1155. Snoek FJ, Skinner TC. Psychological counselling in problematic
Skovlund SE. Psychosocial problems and barriers to improved diabetes diabetes: does it help? Diabet Med [Internet]. 2002 [cited 2022
management: results of the Cross-National Diabetes Attitudes, Wishes Aug 13];19(4):265–73. Available from: https://
and Needs (DAWN) Study. Diabet Med [Internet]. 2005 Oct [cited pubmed.ncbi.nlm.nih.gov/11942996/
2022 Aug 13];22(10):1379–85. Available from: https:// 1156. Dutta D, Ghosh S. Young-onset diabetes: An Indian perspective.
pubmed.ncbi.nlm.nih.gov/16176200/ Indian J Med Res. 2019;149(4):441–2.
1142. Powers MA, Bardsley J, Cypress M, Duker P, Funnell MM, Fischl 1157. Pratt JSA, Browne A, Browne NT, Bruzoni M, Cohen M, Desai A,
AH, et al. Diabetes Self-management Education and Support in Type 2 et al. ASMBS pediatric metabolic and bariatric surgery guidelines, 2018.
Diabetes: A Joint Position Statement of the American Diabetes Surgery for Obesity and Related Diseases. 2018 Jul;14(7):882–901.
Association, the American Association of Diabetes Educators, and the 1158. Narayan KM, Fagot-Campagna A, Imperatore G. Type 2 diabetes
Academy of Nutrition and Dietetics. Clin Diabetes [Internet]. 2016 [cited in children: a problem lurking for India? Indian Pediatr. 2001
2022 Aug 13];34(2):70. Available from: /pmc/articles/PMC4833481/ Jul;38(7):701–4.
1143. Bhardwaj S, Misra A. Obesity, diabetes and the Asian phenotype. 1159. Nakagami T, Qiao Q, Carstensen B, Nhr-Hansen C, Hu G,
World Rev Nutr Diet [Internet]. 2015 [cited 2022 Aug 13];111:116–22. Tuomilehto J, et al. Age, body mass index and Type 2 diabetes-
Available from: https://pubmed.ncbi.nlm.nih.gov/25418400/ associations modified by ethnicity. Diabetologia. 2003
Aug;46(8):1063–70.
1160. Anjana RM, Pradeepa R, Deepa M, Datta M, Sudha V, 1173. Yajnik CS. The insulin resistance epidemic in India: fetal origins,
Unnikrishnan R, et al. Prevalence of diabetes and prediabetes (impaired later lifestyle, or both? Nutr Rev [Internet]. 2001 [cited 2022 Aug 9];59(1
fasting glucose and/or impaired glucose tolerance) in urban and rural Pt 1):1–9. Available from: https://pubmed.ncbi.nlm.nih.gov/11281246/
India: Phase I results of the Indian Council of Medical Research–INdia 1174. Yajnik CS, Fall CHD, Coyaji KJ, Hirve SS, Rao S, Barker DJP,
DIABetes (ICMR–INDIAB) study. Diabetologia. 2011 et al. Neonatal anthropometry: the thin-fat Indian baby. The Pune
Dec 30;54(12):3022–7. Maternal Nutrition Study. Int J Obes Relat Metab Disord [Internet].
1161. Bhatia V, Arya V, Dabadghao P, Balasubramanian K, Sharma K, 2003 Feb 1 [cited 2022 Aug 9];27(2):173–80. Available from: https://
Verghese N, et al. Etiology and outcome of childhood and adolescent pubmed.ncbi.nlm.nih.gov/12586996/
diabetes mellitus in North India. J Pediatr Endocrinol Metab [Internet]. 1175. Deepa R, Sreedharan S, Mohan V. Abdominal obesity, visceral fat
2004 [cited 2022 Aug 9];17(7):993–9. Available from: https:// and Type 2 diabetes - “Asian Indian Phenotype.” Type 2 Diabetes in
pubmed.ncbi.nlm.nih.gov/15301047/ South Asians: Epidemiology, Risk Factors and Prevention. 2006
1162. Mohan V, Deepa M, Deepa R, Shanthirani CS, Farooq S, Ganesan Jan 1;138–52.
A, et al. Secular trends in the prevalence of diabetes and impaired glucose 1176. Lynch JL, Barrientos-Pérez M, Hafez M, Jalaludin MY,
tolerance in urban South India–the Chennai Urban Rural Epidemiology Kovarenko M, Rao PV, et al. Country-Specific Prevalence and
Study (CURES-17). Diabetologia [Internet]. 2006 Jun [cited 2022 Incidence of Youth-Onset Type 2 Diabetes: A Narrative Literature
Aug 9];49(6):1175–8. Available from: https://pubmed.ncbi.nlm.nih.gov/ Review. Ann Nutr Metab. 2020;76(5):289–96.
16570158/ 1177. Praveen PA, Madhu SV, Viswanathan M, Das S, Kakati S, Shah N,
1163. Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. et al. Demographic and clinical profile of youth onset diabetes patients in
Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res. India-Results from the baseline data of a clinic based registry of people
2007 Mar;125(3):217–30. with diabetes in India with young age at onset-[YDR-02]. Pediatr
1164. Ramachandran A, Mohan V, Snehalatha C, Bharani G, Diabetes. 2021;22(1):15–21.
Chinnikrishnudu M, Mohan R, et al. Clinical features of diabetes in the 1178. Mehreen TS, Kamalesh R, Pandiyan D, Kumar DS, Anjana RM,
young as seen at a diabetes centre in south India. Diabetes Res Clin Pract Mohan V, et al. Incidence and Predictors of Dysglycemia and Regression
[Internet]. 1988 [cited 2022 Aug 9];4(2):117–25. Available from: https:// to Normoglycemia in Indian Adolescents and Young Adults: 10-Year
pubmed.ncbi.nlm.nih.gov/3125028/ Follow-Up of the ORANGE Study. Diabetes Technol Ther.
1165. Ramachandran A, Snehalatha C, Kapur A, Vijay V, Mohan V, Das 2020;22(12):875–82.
AK, et al. High prevalence of diabetes and impaired glucose tolerance in 1179. Kumar P, Srivastava S, Mishra PS, Mooss ETK. Prevalence of pre-
India: National Urban Diabetes Survey. Diabetologia [Internet]. 2001 diabetes/type 2 diabetes among adolescents (10-19 years) and its associ-
[cited 2022 Aug 9];44(9):1094–101. Available from: https:// ation with different measures of overweight/obesity in India: a gendered
pubmed.ncbi.nlm.nih.gov/11596662/ perspective. BMC Endocr Disord. 2021 Jul 7;21(1):146.
1166. Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay 1180. Lascar N, Brown J, Pattison H, Barnett AH, Bailey CJ, Bellary S.
V. Type 2 diabetes in Asian-Indian urban children. Diabetes Care Type 2 diabetes in adolescents and young adults. Lancet Diabetes
[Internet]. 2003 Apr 1 [cited 2022 Aug 9];26(4):1022–5. Available from: Endocrinol [Internet]. 2018 Jan 1 [cited 2022 Aug 9];6(1):69–80.
1167. Cheung JTK, Lau E, Tsui CCT, Siu ELN, Tse NKW, Hui NYL, 1181. Prasad RB, Asplund O, Shukla SR, Wagh R, Kunte P, Bhat D, et al.
et al. Combined associations of family history and self-management with Subgroups of patients with young-onset type 2 diabetes in India reveal
age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 insulin deficiency as a major driver. Diabetologia. 2022;65(1):65–78.
diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 coun- 1182. Siddiqui MK, Anjana RM, Dawed AY, Martoeau C, Srinivasan S,
tries. BMC Med. 2022;20(1):249. Saravanan J, et al. Young-onset diabetes in Asian Indians is associated
1168. Saboo B, Agarwal S, Gupta S, Makkar B, Panneerselvam A, Sahoo with lower measured and genetically determined beta cell function.
AK, et al. REAL-world evidence of risk factors and comorbidities in Diabetologia. 2022 Jun 5;65(6):973–83.
YOUNG Indian adults with type 2 diabetes mellitus: A REAL 1183. Baldi JC, Manning PJ, Hofman PL, Walker RJ. Comment on:
YOUNG (diabetes) study. J Family Med Prim Care. 2021 TODAY Study Group. Effects of metformin, metformin plus rosiglita-
Sep;10(9):3444–52. zone, and metformin plus lifestyle on insulin sensitivity and β-cell func-
1169. Ramachandran A, Snehalatha C, Viswanathan V, Viswanathan M, tion in TODAY. Diabetes Care 2013;36:1749-1757. Diabetes Care
Haffner SM. Risk of noninsulin dependent diabetes mellitus conferred by [Internet]. 2013 Dec [cited 2022 Aug 9];36(12). Available from: https://
obesity and central adiposity in different ethnic groups: a comparative pubmed.ncbi.nlm.nih.gov/24265392/
analysis between Asian Indians, Mexican Americans and Whites. 1184. Nanayakkara N, Curtis AJ, Heritier S, Gadowski AM, Pavkov ME,
Diabetes Res Clin Pract [Internet]. 1997 May [cited 2022 Kenealy T, et al. Impact of age at type 2 diabetes mellitus diagnosis on
Aug 9];36(2):121–5. Available from: https://pubmed.ncbi.nlm.nih.gov/ mortality and vascular complications: systematic review and meta-analy-
9229196/ ses. Diabetologia. 2021;64(2):275–87.
1170. Sharp PS, Mohan V, Levy JC, Mather HM, Kohner EM. Insulin 1185. Amutha A, Ranjit U, Anjana RM, Shanthi R CS, Rajalakshmi R,
resistance in patients of Asian Indian and European origin with non- Venkatesan U, et al. Clinical profile and incidence of microvascular com-
insulin dependent diabetes. Horm Metab Res [Internet]. 1987 [cited plications of childhood and adolescent onset type 1 and type 2 diabetes
2022 Aug 9];19(2):84–5. Available from: https:// seen at a tertiary diabetes center in India. Pediatr Diabetes.
pubmed.ncbi.nlm.nih.gov/3549505/ 2021;22(1):67–74.
1171. Ramachandran A, Snehalatha C, Dharmaraj D, Viswanathan M. 1186. Unnikrishnan R, Anjana RM, Amutha A, Ranjani H, Jebarani S,
Prevalence of glucose intolerance in Asian Indians. Urban-rural differ- Ali MK, et al. Younger-onset versus older-onset type 2 diabetes: Clinical
ence and significance of upper body adiposity. Diabetes Care. 1992 profile and complications. J Diabetes Complications. 2017
Oct;15(10):1348–55. Jun;31(6):971–5.
1172. Ramachandran A, Snehalatha C, Latha E, Manoharan M, Vijay V. 1187. Joseph TP, Kotecha NS, Kumar H B C, Jain N, Kapoor A, Kumar
Impacts of urbanisation on the lifestyle and on the prevalence of diabetes S, et al. Coronary artery calcification, carotid intima-media thickness and
in native Asian Indian population. Diabetes Res Clin Pract [Internet]. cardiac dysfunction in young adults with type 2 diabetes mellitus. J
1999 Jun [cited 2022 Aug 9];44(3):207–13. Available from: https:// Diabetes Complications. 2020;34(8):107609.
1188. Reinehr T. Type 2 diabetes mellitus in children and adolescents. 1207. Yu L, Zeng XL, Cheng ML, Yang GZ, Wang B, Xiao ZW, et al.
World J Diabetes [Internet]. 2013 [cited 2022 Aug 9];4(6):270. Available Quantitative assessment of the effect of pre-gestational diabetes and risk
from: https://pubmed.ncbi.nlm.nih.gov/24379917/ of adverse maternal, perinatal and neonatal outcomes. Oncotarget. 2017
1189. Screening for Type 2 Diabetes in Children and Adolescents. AAP Sep 5;8(37):61048–56.
Grand Rounds. 2017 Mar 1;37(3):35–35. 1208. Diagnosis & Management of Gestational Diabetes Mellitus(2021)
1190. Sahoo S, Zaidi G, Vipin V, Chapla A, Thomas N, Yu L, et al. by-Diabetes in Pregnancy study Group India.
Heterogeneity in the aetiology of diabetes mellitus in young adults: A 1209. Hod M, Kapur A, Sacks DA, Hadar E, Agarwal M, di Renzo GC,
prospective study from north India. Indian Journal of Medical Research. et al. The International Federation of Gynecology and Obstetrics (FIGO)
2019;149(4):479. Initiative on gestational diabetes mellitus: A pragmatic guide for diagno-
1191. Wittmeier KDM, Wicklow BA, Sellers EAC, Griffith ATR, Dean sis, management, and care. Int J Gynaecol Obstet [Internet]. 2015 Oct
HJ, McGavock JM. Success with lifestyle monotherapy in youth with [cited 2022 Sep 1];131 Suppl 3:S173–211. Available from: https://
new-onset type 2 diabetes. Paediatr Child Health [Internet]. 2012 [cited pubmed.ncbi.nlm.nih.gov/29644654/
2022 Aug 9];17(3):129–32. Available from: https:// 1210. 2. Classification and Diagnosis of Diabetes: Standards of Medical
pubmed.ncbi.nlm.nih.gov/23449816/ Care in Diabetes—2022. Diabetes Care. 2022
1192. Kautiainen S, Koivusilta L, Lintonen T, Virtanen SM, Rimpelä A. Jan 1;45(Supplement_1):S17–38.
Use of information and communication technology and prevalence of 1211. 15. Management of Diabetes in Pregnancy: Standards of Medical
overweight and obesity among adolescents. Int J Obes (Lond). 2005 Care in Diabetes—2022. Diabetes Care. 2022
Aug;29(8):925–33. Jan 1;45(Supplement_1):S232–43.
1193. TODAY Study Group, Zeitler P, Hirst K, Pyle L, Linder B, 1212. Diabetes in pregnancy:management from preconception to the
Copeland K, et al. A clinical trial to maintain glycemic control in youth postnatal period [Internet]. 2022. Available from: https://
with type 2 diabetes. N Engl J Med. 2012 Jun 14;366(24):2247–56. www.nice.org.uk/terms-and-
1194. Amutha A, Praveen PA, Hockett CW, Ong TC, Jensen ET, Isom 1213. Young EC, Pires MLE, Marques LPJ, de Oliveira JEP, Zajdenverg
SP, et al. Treatment regimens and glycosylated hemoglobin levels in L. Effects of pregnancy on the onset and progression of diabetic nephrop-
youth with Type 1 and Type 2 diabetes: Data from SEARCH (United athy and of diabetic nephropathy on pregnancy outcomes. Diabetes &
States) and YDR (India) registries. Pediatr Diabetes. 2021;22(1):31–9. Metabolic Syndrome: Clinical Research & Reviews. 2011 Jul;5(3):137–
1195. RISE Consortium. Impact of Insulin and Metformin Versus 42.
Metformin Alone on β-Cell Function in Youth With Impaired Glucose 1214. Blumer I, Hadar E, Hadden DR, Jovanovič L, Mestman JH, Murad
Tolerance or Recently Diagnosed Type 2 Diabetes. Diabetes Care. MH, et al. Diabetes and Pregnancy: An Endocrine Society Clinical
2018;41(8):1717–25. Practice Guideline. J Clin Endocrinol Metab. 2013 Nov 1;98(11):4227–
1196. Arslanian SA, Hannon T, Zeitler P, Chao LC, Boucher-Berry C, 49.
Barrientos-Pérez M, et al. Once-Weekly Dulaglutide for the Treatment of 1215. Kitzmiller JL, Block JM, Brown FM, Catalano PM, Conway DL,
Youths with Type 2 Diabetes. New England Journal of Medicine Coustan DR, et al. Managing Preexisting Diabetes for Pregnancy.
[Internet]. 2022 Aug 4 [cited 2022 Sep 15];387(5):433–43. Available Diabetes Care. 2008 May 1;31(5):1060–79.
from: https://www.nejm.org/doi/full/10.1056/NEJMoa2204601 1216. ACOG Practice Bulletin No. 201: Pregestational Diabetes Mellitus.
1197. Veeraswamy S, Divakar H, Gupte S, Datta M, Kapur A, Vijayam Obstetrics & Gynecology. 2018 Dec;132(6):e228–48.
B. Need for testing glucose tolerance in the early weeks of pregnancy. 1217. Evers IM, de Valk HW, Visser GHA. Risk of complications of
Indian J Endocrinol Metab [Internet]. 2016 Jan 1 [cited 2022 Sep pregnancy in women with type 1 diabetes: nationwide prospective study
1];20(1):43. Available from: /pmc/articles/PMC4743382/ in the Netherlands. BMJ. 2004 Apr 17;328(7445):915.
1198. Barker DJP. The developmental origins of adult disease. J Am Coll 1218. Bryant SN, Herrera CL, Nelson DB, Cunningham FG. Diabetic
Nutr [Internet]. 2004 Dec 1 [cited 2022 Sep 1];23(6 Suppl):588S-595S. ketoacidosis complicating pregnancy. J Neonatal Perinatal Med. 2017
Available from: https://pubmed.ncbi.nlm.nih.gov/15640511/ Apr 11;10(1):17–23.
1199. Maternal Health :: National Health Mission [Internet]. [cited 2022 1219. Buschur E, Stetson B, Barbour LA. Diabetes In Pregnancy. 2000.
Sep 1]. Available from: http://nhm.gov.in/ 1220. Kalra B, Gupta Y, Kalra S. Pre-conception management of diabe-
index1.php?lang=1&level=2&sublinkid=822&lid=218 tes. J Pak Med Assoc. 2015 Nov;65(11):1242–3.
1200. Diagnosis & Management of Gestational Diabetes Mellitus 1221. American Diabetes Association. 14. Management of Diabetes in
Technical and Operational Guidelines. Pregnancy: Standards of Medical Care in Diabetes-2019. Diabetes Care.
1201. Evers IM, de Valk HW, Visser GHA. Risk of complications of 2019;42(Suppl 1):S165–72.
pregnancy in women with type 1 diabetes: nationwide prospective study 1222. 36th International Symposium on Intensive Care and Emergency
in the Netherlands. BMJ. 2004 Apr 17;328(7445):915. Medicine : Brussels, Belgium. 15-18 March 2016. Crit Care.
1202. Lawrence JM, Contreras R, Chen W, Sacks DA. Trends in the 2016;20(Suppl 2):94.
Prevalence of Preexisting Diabetes and Gestational Diabetes Mellitus 1223. Magee LA, von Dadelszen P, Rey E, Ross S, Asztalos E, Murphy
Among a Racially/Ethnically Diverse Population of Pregnant Women, KE, et al. Less-tight versus tight control of hypertension in pregnancy. N
1999–2005. Diabetes Care. 2008 May 1;31(5):899–904. Engl J Med. 2015 Jan 29;372(5):407–17.
1203. Ramadevi V. Prevalence of pre-gestational diabetes in pregnancy. 1224. Wild R, Weedin EA, Gill EA. Women’s Health Considerations for
MedPulse-International Journal of Gynaecology [Internet]. Lipid Management. Cardiol Clin. 2015 May;33(2):217–31.
2017;3(3):80–3. Available from: http://medpulse.in/Gynacology/ 1225. Yehuda I. Implementation of Preconception Care for Women With
index.php Diabetes. Diabetes Spectr. 2016 May;29(2):105–14.
1204. S. R. R, Lekshmi ST, Chellamma N. Prevalence of pre-gestational 1226. American Diabetes Association. Preconception care of women
diabetes among the antenatal women attending a tertiary care center. Int J with diabetes. Diabetes Care. 2004 Jan;27 Suppl 1:S76-8.
Reprod Contracept Obstet Gynecol. 2017 Feb 19;6(3):797. 1227. Hassanein M, Al-Arouj M, Hamdy O, Bebakar WMW, Jabbar A,
1205. Wahabi HA, Esmaeil SA, Fayed A, Al-Shaikh G, Alzeidan RA. Al-Madani A, et al. Diabetes and Ramadan: Practical guidelines. Diabetes
Pre-existing diabetes mellitus and adverse pregnancy outcomes. BMC Res Clin Pract. 2017 Apr;126:303–16.
Res Notes. 2012 Dec 10;5(1):496. 1228. Ringholm L, Do NC, Damm P, Mathiesen ER. Pregnancy out-
1206. Negrato CA, Mattar R, Gomes MB. Adverse pregnancy outcomes comes in women with type 1 diabetes using insulin degludec. Acta
in women with diabetes. Diabetol Metab Syndr. 2012 Dec 11;4(1):41. Diabetol. 2022 May 11;59(5):721–7.
1229. Correa A, Gilboa SM, Botto LD, Moore CA, Hobbs CA, Cleves 1249. Glandt M, Bloomgarden ZT. Hypertension in diabetes: treatment
MA, et al. Lack of periconceptional vitamins or supplements that contain considerations. J Clin Hypertens (Greenwich). 2011 Apr;13(4):314–8.
folic acid and diabetes mellitus-associated birth defects. Am J Obstet 1250. DIABHYCAR Study - Ramipril and Cardiovascular and Renal
Gynecol. 2012 Mar;206(3):218.e1-13. Outcomes in Type 2 Diabetes [Internet]. [cited 2022 Sep 15]. Available
1230. Majra JP, Verma R. Opportunistic screening for random blood from: https://www.ebmconsult.com/articles/diabhycar-study-ramipril-
glucose level among adults attending a rural tertiary care centre in and-cardiovascular-and-renal-outcomes-in-type-2-diabetes
Haryana during world health day observation activity. Int J Community 1251. Menne J, Ritz E, Ruilope LM, Chatzikyrkou C, Viberti G, Haller
Med Public Health. 2017 May 22;4(6):1951. H. The Randomized Olmesartan and Diabetes Microalbuminuria
1231. Lin CS, Chang CC, Lee YW, Liu CC, Yeh CC, Chang YC, et al. Prevention (ROADMAP) Observational Follow‐Up Study: Benefits of
Adverse Outcomes after Major Surgeries in Patients with Diabetes: A RAS Blockade With Olmesartan Treatment Are Sustained After Study
Multicenter Matched Study. J Clin Med. 2019 Jan 16;8(1). Discontinuation. Journal of the American Heart Association:
1232. Barrett HL, Morris J, McElduff A. Watchful waiting: a manage- Cardiovascular and Cerebrovascular Disease [Internet]. 2014 [cited
ment protocol for maternal glycaemia in the peripartum period. Aust N Z 2022 Sep 15];3(2). Available from: /pmc/articles/PMC4187490/
J Obstet Gynaecol. 2009 Apr;49(2):162–7. 1252. Cheng J, Zhang W, Zhang X, Han F, Li X, He X, et al. Effect of
1233. Mitanchez D, Yzydorczyk C, Simeoni U. What neonatal compli- Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor
cations should the pediatrician be aware of in case of maternal gestational Blockers on All-Cause Mortality, Cardiovascular Deaths, and
diabetes? World J Diabetes. 2015 Jun 10;6(5):734–43. Cardiovascular Events in Patients With Diabetes Mellitus: A Meta-ana-
1234. Parks C, Peipert JF. Eliminating health disparities in unintended lysis. JAMA Intern Med [Internet]. 2014 May 1 [cited 2022 Sep
pregnancy with long-acting reversible contraception (LARC). Am J 15];174(5):773–85. Available from: https://jamanetwork.com/journals/
Obstet Gynecol. 2016;214(6):681–8. jamainternalmedicine/fullarticle/1847572
1235. Fundoiano-Hershcovitz Y, Bacher D, Ritholz MD, Horwitz DL, 1253. Ganesh J, Viswanathan V. Management of diabetic hypertensives.
Manejwala O, Goldstein P. Blood Pressure Monitoring as a Digital Indian J Endocrinol Metab. 2011 Oct;15 Suppl 4:S374-9.
Health Tool for Improving Diabetes Clinical Outcomes: Retrospective 1254. Kumar V. How to live well in old age? Journal of the Indian
Real-world Study. J Med Internet Res [Internet]. 2022 Feb 1 [cited Academy of Geriatrics [Internet]. 2021 [cited 2022 Aug 8];17(1):43.
2022 Sep 14];24(2). Available from: /pmc/articles/PMC8864523/ Available from: http://www.jiag.com/article.asp?issn=0974-
1236. Nugroho P, Andrew H, Kohar K, Noor CA, Sutranto AL. 3405;year=2021;volume=17;issue=1;spage=43;epage=48;aulast=Kumar
Comparison between the world health organization (WHO) and interna- 1255. v Kumar. Geriatric assessment screening: further observations on
tional society of hypertension (ISH) guidelines for hypertension. Ann the AIIMS experience. . In: Kumar V, editor. Aging: Indian Perspective
Med. 2022;54(1):837–45. and Global Scenario (ed. New Delhi: Balaji Printers; 1996.
1237. American Diabetes Association Professional Practice Committee. 1256. Kumar V. Vaccination for elderly people. . Kumar V, editor. Vol.
10. Cardiovascular Disease and Risk Management: Standards of Medical XVII. 2014. 283–289 p.
Care in Diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S144–74. 1257. Mitra MPP. National Policy for Senior Citizens. 2011.
1238. Nugroho P, Andrew H, Kohar K, Noor CA, Sutranto AL. 1258. International Institute for Population Sciences (IIPS), NPHCE,
Comparison between the world health organization (WHO) and interna- MoHFW, Harvard T. H. Chan School of Public Health (HSPH),
tional society of hypertension (ISH) guidelines for hypertension. Ann University of Southern California (USC). Longitudinal Ageing Study in
Med. 2022;54(1):837–45. India (LASI). Mumbai; 2020.
1239. Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, 1259. Pradeepa R, Mohan V. Epidemiology of type 2 diabetes in India.
Prabhakaran D, et al. 2020 International Society of Hypertension Indian J Ophthalmol [Internet]. 2021 Nov 1 [cited 2022
Global Hypertension Practice Guidelines. Hypertension. 2020 Aug 8];69(11):2932–8. Available from: https://
Jun;75(6):1334–57. pubmed.ncbi.nlm.nih.gov/34708726/
1240. Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and 1260. Schernthaner G, Schernthaner-Reiter MH. Diabetes in the older
Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. patient: heterogeneity requires individualisation of therapeutic strategies.
Canadian Journal of Cardiology. 2018 May;34(5):575–84. Diabetologia. 2018 Jul 7;61(7):1503–16.
1241. Geldsetzer P, Manne-Goehler J, Theilmann M, Davies JI, Awasthi 1261. Kumar V. RSSDI Update Section 5 on Diabetes in the elderly:
A, Vollmer S, et al. Diabetes and Hypertension in India. JAMA Intern Glycaemic control in elderly diabetics with dementia. Research Society
Med. 2018 Mar 1;178(3):363. for the Study of Diabetes in India. Lucknow; 2015. p. 50–5.
1242. Sinha S, Haque M. Insulin Resistance Is Cheerfully Hitched with 1262. Chawla R, Madhu S v., Makkar BM, Ghosh S, Saboo B, Kalra S.
Hypertension. Life (Basel). 2022 Apr 10;12(4). RSSDI-ESI Clinical Practice Recommendations for the Management of
1243. A Randomized Trial of Intensive versus Standard Blood-Pressure Type 2 Diabetes Mellitus 2020. Int J Diabetes Dev Ctries.
Control. New England Journal of Medicine. 2015 Nov 26;373(22):2103– 2020;40(S1):25–8.
16. 1263. Gupta A, K. Inamadar S, Goel A. The New Geriatric Syndromes.
1244. Glandt M, Bloomgarden ZT. Hypertension in Diabetes: Treatment Journal of the Indian Academy of Geriatrics. 2019 Mar 1;15(1):33–6.
Considerations. The Journal of Clinical Hypertension. 2011 1264. Scelzo A, di Somma S, Antonini P, Montross LP, Schork N,
Apr;13(4):314–8. Brenner D, et al. Mixed-methods quantitative-qualitative study of 29
1245. Patil M, Jose AP, More A, Maheshwari A, Verma N, Shah R, et al. nonagenarians and centenarians in rural Southern Italy: focus on positive
May Measurement Month 2019: an analysis of blood pressure screening psychological traits. Int Psychogeriatr [Internet]. 2018 Jan 1 [cited 2022
results from India. Eur Heart J Suppl. 2021 May;23(Suppl B):B73–6. Aug 8];30(1):31–8. Available from: https://pubmed.ncbi.nlm.nih.gov/
1246. Gupta R, Deedwania PC, Achari V, Bhansali A, Gupta BK, Gupta 29229012/
A, et al. Normotension, prehypertension, and hypertension in urban 1265. Thomas ML, Kaufmann CN, Palmer BW, Depp CA, Martin AS,
middle-class subjects in India: prevalence, awareness, treatment, and con- Glorioso DK, et al. Paradoxical Trend for Improvement in Mental Health
trol. Am J Hypertens. 2013 Jan;26(1):83–94. with Aging: A Community-Based Study of 1,546 Adults Aged 21–100
1247. Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Years. J Clin Psychiatry [Internet]. 2016 Aug 1 [cited 2022
Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Aug 8];77(8):e1019. Available from: /pmc/articles/PMC5461877/
Canadian Journal of Cardiology. 2018 May;34(5):575–84. 1266. Brown-O’Hara T. Geriatric syndromes and their implications for
1248. Naha S, Gardner MJ, Khangura D, Kurukulasuriya R, Sowers JR. nursing. Nursing (Brux). 2013 Jan;43(1):1–3.
Hypertension in Diabetes. In: Endotext. 2000.
1267. Rosen SL, Reuben DB. Geriatric Assessment Tools. Mount Sinai 1283. Landgraf R. Meglitinide Analogues in the Treatment of Type 2
Journal of Medicine: A Journal of Translational and Personalized Diabetes Mellitus. Drugs Aging. 2000 Nov;17(5):411–25.
Medicine [Internet]. 2011 Jul 1 [cited 2022 Aug 9];78(4):489–97. 1284. Meier JJ. Efficacy of Semaglutide in a Subcutaneous and an Oral
Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/ Formulation. Front Endocrinol (Lausanne) [Internet]. 2021 Jun 25 [cited
msj.20277 2022 Aug 8];12. Available from: /pmc/articles/PMC8269445/
1268. Ganguli M, Ratcliff G, Chandra V, Sharma S, Gilby J, Pandav R, 1285. Munshi MN, Slyne C, Segal AR, Saul N, Lyons C, Weinger K.
et al. A hindi version of the MMSE: The development of a cognitive Simplification of Insulin Regimen in Older Adults and Risk of
screening instrument for a largely illiterate rural elderly population in Hypoglycemia. JAMA Intern Med [Internet]. 2016 Jul 1 [cited 2022
india. Int J Geriatr Psychiatry. 1995 May;10(5):367–77. Aug 8];176(7):1023–5. Available from: https://
1269. Borson S, Scanlan JM, Chen P, Ganguli M. The Mini-Cog as a pubmed.ncbi.nlm.nih.gov/27273335/
screen for dementia: Validation in a population-based sample. J Am 1286. Bruce Bode. Liraglutide: a review of the first once-daily GLP-1
Geriatr Soc. 2003 Oct 1;51(10):1451–4. receptor agonist. American Journal of Managed Care. 2011;17:59–70.
1270. Kumar V. Frailty and its significance in old age. In: Clinical 1287. Karagiannis T, Tsapas A, Athanasiadou E, Avgerinos I, Liakos A,
Medicine Update, Vol 22 Proc IACMCON. Greater Noida; 2019. p. Matthews DR, et al. GLP-1 receptor agonists and SGLT2 inhibitors for
488–92. older people with type 2 diabetes: A systematic review and meta-analysis.
1271. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Diabetes Res Clin Pract [Internet]. 2021 Apr 1 [cited 2022 Aug 8];174.
Gottdiener J, et al. Frailty in Older Adults: Evidence for a Phenotype. J Available from: https://pubmed.ncbi.nlm.nih.gov/33705820/
Gerontol A Biol Sci Med Sci. 2001 Mar 1;56(3):M146–57. 1288. Barbagallo M, Dominguez LJ. Type 2 diabetes mellitus and
1272. Gunasekaran V, Subramanian MS, Singh V, Dey AB. Outcome of Alzheimer’s disease. World J Diabetes [Internet]. 2014 Dec 12 [cited
older adults at risk of frailty. AGING MEDICINE. 2021 2022 Aug 8];5(6):889. Available from: /pmc/articles/PMC4265876/
Dec 12;4(4):266–71. 1289. Matfin G, van Brunt K, Zimmermann AG, Threlkeld R, Ignaut DA.
1273. American Diabetes Association Professional Practice Committee, Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen
Draznin B, Aroda VR, Bakris G, Benson G, Brown FM, et al. Older in Injection-Naïve Patients With Type 2 Diabetes. J Diabetes Sci Technol
Adults: Standards of Medical Care in Diabetes-2022. Diabetes Care. [Internet]. 2015 Sep 1 [cited 2022 Aug 8];9(5):1071–9. Available from:
2022;45(Suppl 1):S195–207. https://pubmed.ncbi.nlm.nih.gov/25901022/
1274. Kalra S, Unnikrishnan AG, Baruah MP. Interaction, information, 1290. MAMI YOSHIDA, TAKAKO MORIMOTO, ERIKO OH,
involvement (the 3I strategy): Rebuilding trust in the medical profession. NAOMUNE YAMAMOTO, KOUJI NAGATA, AKIO SAEKI, et al.
Indian J Endocrinol Metab. 2017 Mar 1;21(2):268–70. Possibility of liraglutide for prevention of dementia progression in pa-
1275. JP B, J WR, AL A, CM A, NG C, MJ F, et al. Nutrition recom- tients with type 2 diabetes. In: Possibility of Liraglutide for Prevention of
mendations and interventions for diabetes: a position statement of the Dementia Progression in Patients with Type 2 Diabetes. Orlando; 2018.
American Diabetes Association. Diabetes Care [Internet]. 2008 Jan [cited 1291. Perna S, Guido D, Bologna C, Solerte SB, Guerriero F, Isu A, et al.
2022 Aug 8];31 Suppl 1(SUPPL. 1). Available from: https:// Liraglutide and obesity in elderly: efficacy in fat loss and safety in order to
pubmed.ncbi.nlm.nih.gov/18165339/ prevent sarcopenia. A perspective case series study. Aging Clin Exp Res
1276. Min J, Kim SY, Shin IS, Park YB, Lim YW. The Effect of Meal [Internet]. 2016 Dec 1 [cited 2022 Aug 8];28(6):1251–7. Available from:
Replacement on Weight Loss According to Calorie-Restriction Type and https://pubmed.ncbi.nlm.nih.gov/26749118/
Proportion of Energy Intake: A Systematic Review and Meta-Analysis of 1292. Hanefeld M, Berria R, Lin J, Aronson R, Darmon P, Evans M, et al.
Randomized Controlled Trials. J Acad Nutr Diet [Internet]. 2021 Aug 1 Lixisenatide treatment for older patients with type 2 diabetes mellitus
[cited 2022 Aug 8];121(8):1551-1564.e3. Available from: https:// uncontrolled on oral antidiabetics: meta-analysis of five randomized con-
pubmed.ncbi.nlm.nih.gov/34144920/ trolled trials. Adv Ther [Internet]. 2014 Aug 1 [cited 2022
1277. Henry CJ, Quek RYC, Kaur B, Shyam S, Singh HKG. A Aug 8];31(8):861–72. Available from: https://pubmed.ncbi.nlm.nih.gov/
glycaemic index compendium of non-western foods. Nutr Diabetes 25143188/
[Internet]. 2021 Jun 1 [cited 2022 Aug 8];11(1). Available from: https:// 1293. Frier BM. How hypoglycaemia can affect the life of a person with
pubmed.ncbi.nlm.nih.gov/33414403/ diabetes. Diabetes Metab Res Rev [Internet]. 2008 Feb [cited 2022
1278. Vlachos D, Malisova S, Lindberg FA, Karaniki G. Glycemic Index Aug 8];24(2):87–92. Available from: https://pubmed.ncbi.nlm.nih.gov/
(GI) or Glycemic Load (GL) and Dietary Interventions for Optimizing 18088077/
Postprandial Hyperglycemia in Patients with T2 Diabetes: A Review. 1294. Frier BM. Hypoglycaemia in diabetes mellitus: epidemiology and
Nutrients [Internet]. 2020 Jun 1 [cited 2022 Aug 8];12(6). Available clinical implications. Nat Rev Endocrinol [Internet]. 2014 [cited 2022
from: /pmc/articles/PMC7352659/ Aug 8];10(12):711–22. Available from: https://
1279. Wong E, Backholer K, Gearon E, Harding J, Freak-Poli R, pubmed.ncbi.nlm.nih.gov/25287289/
Stevenson C, et al. Diabetes and risk of physical disability in adults: A 1295. Action to Control Cardiovascular Risk in Diabetes Study Group,
systematic review and meta-analysis. Lancet Diabetes Endocrinol Gerstein HC, Miller ME, Byington RP, Goff DC, Bigger JT, et al. Effects
[Internet]. 2013 Oct 1 [cited 2022 Aug 8];1(2):106–14. Available from: of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008
http://www.thelancet.com/article/S2213858713700469/fulltext Jun 12;358(24):2545–59.
1280. Good CB. Polypharmacy in Elderly Patients With Diabetes. 1296. Meneilly GS, Cheung E, Tuokko H. Altered responses to hypogly-
Diabetes Spectrum. 2002 Oct 1;15(4):240–8. cemia of healthy elderly people. J Clin Endocrinol Metab [Internet]. 1994
1281. Tsai YH, Chuang LL, Lee YJ, Chiu CJ. How Does Diabetes [cited 2022 Aug 8];78(6):1341–8. Available from: https://
Accelerate Normal Aging? An Examination of ADL, IADL, and pubmed.ncbi.nlm.nih.gov/8200936/
Mobility Disability in Middle-aged and Older Adults With and Without 1297. Sircar M, Bhatia A, Munshi M. Review of Hypoglycemia in the
Diabetes. Diabetes Res Clin Pract [Internet]. 2021 Dec 1 [cited 2022 Older Adult: Clinical Implications and Management. Can J Diabetes
Aug 8];182. Available from: https://pubmed.ncbi.nlm.nih.gov/ [Internet]. 2016 Feb 1 [cited 2022 Aug 8];40(1):66–72. Available from:
34756960/ https://pubmed.ncbi.nlm.nih.gov/26752195/
1282. Mishra V, Nayak P, Sharma M, Albutti A, Alwashmi ASS, Aljasir 1298. Frier B. M., Fisher B. M. Impaired hypoglycaemia awareness.
MA, et al. Emerging Treatment Strategies for Diabetes Mellitus and Chichester: John Wiley; 1999. 111–146 p.
Associated Complications: An Update. Pharmaceutics [Internet]. 2021 1299. Lipska Kasia J, Kosiborod Mikhail. Hypoglycemia and adverse
Oct 1 [cited 2022 Aug 8];13(10). Available from: https:// outcomes: marker or mediator? . Rev Cardiovasc Med. 2011;12:132–5.
1300. Ligthelm RJ, Kaiser M, Vora J, Yale JF. Insulin use in elderly Clin Epidemiol [Internet]. 1992 [cited 2022 Aug 8];45(10):1045–51.
adults: risk of hypoglycemia and strategies for care. J Am Geriatr Soc Available from: https://pubmed.ncbi.nlm.nih.gov/1474400/
[Internet]. 2012 Aug [cited 2022 Aug 8];60(8):1564–70. Available from: 1313. Samsa GP, Hanlon JT, Schmader KE, Weinberger M, Clipp EC,
https://pubmed.ncbi.nlm.nih.gov/22881394/ Uttech KM, et al. A summated score for the medication appropriateness
1301. Campanelli M. Christine. American Geriatrics Society Updated index: development and assessment of clinimetric properties including
Beers Criteria for Potentially Inappropriate Medication Use in Older content validity. J Clin Epidemiol [Internet]. 1994 [cited 2022
Adults. J Am Geriatr Soc. 2012 Apr;60(4):616–31. Aug 8];47(8):891–6. Available from: https://pubmed.ncbi.nlm.nih.gov/
1302. World Health Organization Model List of Essential Medicines. 7730892/
1303. 6. Glycemic Targets: Standards of Medical Care in Diabetes— 1314. Launer LJ, Miller ME, Williamson JD, Lazar RM, Gerstein HC,
2018. Diabetes Care. 2018 Jan 1;41(Supplement_1):S55–64. Murray AM, et al. Effects of intensive glucose lowering on brain structure
1304. Pani LN, Korenda L, Meigs JB, Driver C, Chamany S, Fox CS, and function in people with type 2 diabetes (ACCORD MIND): a
et al. Effect of aging on A1C levels in individuals without diabetes: randomised open-label substudy. Lancet Neurol [Internet]. 2011 Nov
evidence from the Framingham Offspring Study and the National [cited 2022 Aug 8];10(11):969–77. Available from: https://
Health and Nutrition Examination Survey 2001-2004. Diabetes Care pubmed.ncbi.nlm.nih.gov/21958949/
[Internet]. 2008 Oct [cited 2022 Aug 8];31(10):1991–6. Available from: 1315. Du YF, Ou HY, Beverly EA, Chiu CJ. Achieving glycemic control
https://pubmed.ncbi.nlm.nih.gov/18628569/ in elderly patients with type 2 diabetes: a critical comparison of current
1305. Sue Kirkman M, Briscoe VJ, Clark N, Florez H, Haas LB, Halter options. Clin Interv Aging [Internet]. 2014 Nov 18 [cited 2022
JB, et al. Diabetes in older adults: a consensus report. J Am Geriatr Soc Aug 9];9:1963. Available from: /pmc/articles/PMC4241951/
[Internet]. 2012 [cited 2022 Aug 8];60(12):2342–56. Available from: 1316. Singh S, Segal JB. Thiazolidinediones and Macular Edema. Arch
https://pubmed.ncbi.nlm.nih.gov/23106132/ Intern Med. 2012 Jul 9;172(13).
1306. ACCORD Study Group, Buse JB, Bigger JT, Byington RP, 1317. Tuomilehto J, Borch-Johnsen K, Tajima N, Cockram CS,
Cooper LS, Cushman WC, et al. Action to Control Cardiovascular Risk Nakagami T. Cardiovascular risk profile assessment in glucose-
in Diabetes (ACCORD) trial: design and methods. Am J Cardiol. 2007 intolerant Asian individuals–an evaluation of the World Health
Jun 18;99(12A):21i–33i. Organization two-step strategy: the DECODA Study (Diabetes
1307. de Boer IH, Bangalore S, Benetos A, Davis AM, Michos ED, Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia).
Muntner P, et al. Diabetes and Hypertension: A Position Statement by Diabet Med [Internet]. 2002 [cited 2022 Aug 8];19(7):549–57.
the American Diabetes Association. Diabetes Care. 2017;40(9):1273–84. Available from: https://pubmed.ncbi.nlm.nih.gov/12099957/
1308. Chen LK, Chen YM, Lin MH, Peng LN, Hwang SJ. Care of elderly 1318. Munshi MN, Florez H, Huang ES, Kalyani RR, Mupanomunda M,
patients with diabetes mellitus: a focus on frailty. Ageing Res Rev Pandya N, et al. Management of Diabetes in Long-term Care and Skilled
[Internet]. 2010 Nov [cited 2022 Aug 8];9 Suppl 1(SUPPL.). Available Nursing Facilities: A Position Statement of the American Diabetes
from: https://pubmed.ncbi.nlm.nih.gov/20849981/ Association. Diabetes Care [Internet]. 2016 Feb 1 [cited 2022
1309. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is Aug 8];39(2):308–18. Available from: https://pubmed.ncbi.nlm.nih.gov/
polypharmacy? A systematic review of definitions. BMC Geriatr 26798150/
[Internet]. 2017 Oct 10 [cited 2022 Aug 8];17(1):1–10. Available from: 1319. Kumar V, Wig N, Bhatnagar S, Bajaj P, Dey AB, Chakravorti I,
https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-017- et al. Expert Group Draft on Model rules under specifications and stan-
0621-2 dards for home care and hospice care. 2021 Oct.
1310. Jörgensen T, Johansson S, Kennerfalk A, Wallander MA, 1320. Jordan RI, Allsop MJ, ElMokhallalati Y, Jackson CE, Edwards
Svärdsudd KK. Prescription drug use, diagnoses, and healthcare utiliza- HL, Chapman EJ, et al. Duration of palliative care before death in inter-
tion among the elderly. Ann Pharmacother [Internet]. 2001 [cited 2022 national routine practice: a systematic review and meta-analysis. BMC
Aug 8];35(9):1004–9. Available from: https://pubmed.ncbi.nlm.nih.gov/ Med [Internet]. 2020 Dec 1 [cited 2022 Aug 8];18(1). Available from:
11573845/ https://pubmed.ncbi.nlm.nih.gov/33239021/
1311. Fick DM, Semla TP, Steinman M, Beizer J, Brandt N, 1321. RACGP. Diabetes and end-of-life care. In: Management of type 2
Dombrowski R, et al. American Geriatrics Society 2019 Updated AGS diabetes: A handbook for general practice [Internet]. Available from:
Beers Criteria® for Potentially Inappropriate Medication Use in Older www.racgp.org.
Adults. J Am Geriatr Soc [Internet]. 2019 Apr 1 [cited 2022
Aug 8];67(4):674–94. Available from: https://pubmed.ncbi.nlm.nih.gov/
30693946/
1312. Hanlon JT, Schmader KE, Samsa GP, Weinberger M, Uttech KM, Publisher’s note Springer Nature remains neutral with regard to jurisdic-
Lewis IK, et al. A method for assessing drug therapy appropriateness. J tional claims in published maps and institutional affiliations.

Rssdi 2022 T2DM

Uploaded by

Document Informationclick to expand document information

Copyright:

Available Formats

Rssdi 2022 T2DM

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Rssdi 2022 T2DM

Uploaded by

Copyright:

Available Formats

International Journal of Diabetes in Developing Countries (October 2022) 42 (Suppl 1):S1–S143

RSSDI Clinical Practice Recommendations for the Management

Brij Mohan Makkar, Ch.Vasanth Kumar, Banshi Saboo, Sanjay Agarwal

Clinical Practice Recommendations Review Committee

A Ramachandran, Anoop Misra, Banshi Saboo, Brij Mohan Makkar, Ch.

Members: Dr Urman Dhruv, Dr Psychosocial Issues Coordinators: Dr Sanjay Kalra, Dr

For more details on glucose estimation, refer 2

Background - HbA1c ≥6.5% as an optimal level for diagnosis of diabetes in Indian

Strategies have to be formulated considering the cultural, socio-economic

Considerations Relevant To The Development Of Screening Policy

Paramedical personnel Clinical Guidelines on the use of Metformin in Prediabetes

Table 3: Summary of recommendations on use of metformin for

Summary of recommendations on use of metformin for prevention of T2DM

Food groups and patterns

• Nutritional counseling may be provided by health care providers (HCPs) trained in

Limited Care Rationale and Evidence

TREATMENT 2: INJECTABLES insulin-

Consideration Table 5: Clinical situations where the use of injectables is recommended

Intensification of Insulin therapy (Tables # and ##)

Table 6: Choice of insulin therapy

Basal insulin Premixed/co-formulation Prandial insulin

Table 7: Steps for initiating basal insulin

Step 1: Glucose Value TDD

FPG >180 mg/dL Add 4 U

Insulin regimen Characteristics Therapeutic TDD

RSSDI Therapeutic Wheel Background

Recommendations Plasma glucose level (mg/dL) >250 >600

Arterial or venous pH <7.30 >7.30

Table 13: Management of acute metabolic complications

Fluid replacement therapy

Neurological observations for warning signs and Potassium replacement

The maximum recommended rate is 0.5 mmol/kg/h.

The treatment goal is to maintain serum potassium levels of 4-5 mEq/l.

Transition to subcutaneous insulin

To prevent recurrence of ketoacidosis or rebound hyperglycemia, consider the overlap of IV

Regimen and adjust dosage as needed.

SGLT2i: avoid permanently.

DKD, hepatic impairment

Prevention of hypoglycemia Implementations

Background neuropathy, gabapentin monotherapy was efficacious for treating pain

Management of diabetic neuropathy [Figure]

EPE was found to be useful in the serial evaluation of kidney function in

Class Dose adjustments Recommendations

Metformin Metformin can be used till to GFR 30

indicated. Risk classification level Management

Diabetic foot ulcers and peripheral arterial disease

Diabetic foot infections

Management of diabetic foot complications

Table 18: Studies assessing cardiovascular risk factors Management

Blood pressure lowering agents.

Risk Factors Bone turnover markers(BTMs)

A non-invasive imaging test for steatosis is ultrasound (USG) (preferred Metformin

Omega-3 Polyunsaturated Fatty Acid SGLT 2 I

Available choices of weight loss options in patients with T2DM are as

Anti-hyperglycemic Drugs with Potential for Weight Loss

Background ▪ Hepatitis A is the most common vaccine-preventable virus acquired

CLINICAL MONITORING SMBG is an essential component of modern diabetes treatment; it is the

• Regular monitoring of HbA1c will facilitate the identification of patients