Ramadan and Diabetes Care
Ramadan and Diabetes Care
Ramadan and Diabetes Care
Ramadan
and
Diabetes CaRe
Editors
Abdul H Zargar
MD DM
Sanjay Kalra MD DM
Consultant Endocrinologist
Bharti Hospital
Karnal, Haryana, India
Foreword
Sarita Bajaj
MD DM
Contributors
Abdul H Zargar
Jamal Ahmad
MD DM
Abdul Jabbar
Medical Advisor
Dubai, United Arab Emirates
Altamash Shaikh
DNB (Endocrinology)
Consultant Endocrinologist
Saifee Hospital
Mumbai, Maharashtra, India
Anish Ahamed
Director
Centre for Diabetes and Endocrinology
Faculty of Medicine
Jawaharlal Nehru Medical College Hospital
Aligarh Muslim University
Aligarh, Uttar Pradesh, India
Mahdi Kamoun
MD
Manoj Chadha
(Endocrinology) FICP
Consultant
Department of Endocrinology
PD Hinduja Hospital and Research Centre
Mumbai, Maharashtra, India
DM
Ines Slim
MD
Intekhab Ahmed
MD FACP FACE
PhD
Professor
Department of Endocrinology and Diabetes
Hedi Chaker Hospital
Sfax, Tunisia
MD
Rakesh Sahay
Professor of Endocrinology
Osmania Medical College and
Osmania General Hospital
Consultant Endocrinologist and Diabetologist
Mediciti Hospital
Hyderabad, Andhra Pradesh, India
Secretary, Endocrine Society of India
Chairman, AP Chapter of RSSDI
Editor, Journal of Academy of Medical Sciences
Associate Editor, Indian Journal of
Endocrinology and Metabolism
Sarita Bajaj
MD (Medicine) DM (Endocrinology)
MBBS MD (Medicine)
DM (Endocrinology) FACP
Professor
Department of Endocrinology
Sher-e-Kashmir Institute of Medical Sciences
Srinagar, Jammu and Kashmir, India
V Sri Nagesh
MD DM
Consultant Endocrinology,
CARE Hospitals
Hyderabad, Andhra Pradesh, India
Foreword
Most books are labors of love, products of passion, and direct outcomes of determination.
This passion and determination is needed from all stakeholderseditors, contributors
and publishers. If lucky, a few books strike an equally loving and passionate response from
readers.
This well-referenced, pleasantly laid out book, Ramadan and Diabetes Care, under the
editorship of Professor Abdul H Zargar and Dr Sanjay Kalra, has all these elements, and
much more. The editors and contributors have chosen a subject that impacts the lives of
one-third of mankind, yet which we all practice, without any formal training in this field.
The current book synthesizes all available evidence, combines it with experience, and with
what the editors term as logical empiricism. It covers not only the non-pharmacological and
pharmacological management of diabetes in Ramadan, but also addresses issues related
to counseling, to women, and to the young as well as elderly. Detailed pathophysiological
explanations are also provided in the chapter on Endocrinology of Fasting. Contributors
from three continents have contributed to the book and their combined expertise makes
this international masterpiece a joy to possess, and to read.
The motive of the editors and contributors seems to be a rare combination in todays
world, i.e. upliftment and optimization, both of science and spirituality. With the excellent
and exhaustive deliberations on the challenging subject matter done in a practical, readerfriendly manner, I am sure, this book will achieve both aims. I pray that the multiple efforts
behind this book translate into safe, uplifting fasting, for millions of believers across the
world.
Sarita Bajaj
MD DM
Preface
Want to Cure Diabetes? Click Here
Although Islam is the second largest religion worldwide, it bears more than its fair share of
the diabetes pandemic. The brunt of this modern epidemic is felt more acutely by Islamic
countries, which face rapid modernization and urbanization, accompanied by drastic
lifestyle changes.
The Top Ten list (2010), for the number of people with diabetes, lists India (rank 2),
Bangladesh (rank 8), Egypt (rank 9), and Indonesia (rank 10); all these countries have
large populations which believe in Islam. The projected list for 2030 predicts an increase
in the diabetes population in Islamic countries; while India maintains its second position,
Bangladesh (rank 5), Egypt (rank 8), and Indonesia (rank 9), are joined by Pakistan at the 10th
place (International Diabetes Federation, Diabetes Atlas, 5th edition).
The strain of diabetes upon Islamic nations is observed to a much greater extent when
the prevalence of diabetes in adults is measured. The 2011 list ranks the Islamic countries,
i.e. Kuwait (rank 3), Lebanon (rank 5), Qatar (rank 6), Saudi Arabia (rank 7), Bahrain (rank 8)
and United Arab Emirates (UAE) (rank 9) among the 10 nations with highest prevalence of
diabetes. The same risk names figure in the 2030 projection, albeit at different ranks (Saudi
Arabia moves up to 6th place, while Lebanon, Qatar, Bahrain and UAE show a relative
improvement at 7th, 8th, 9th, and 10th positions, respectively).
For adherents of Islam, Ramadan is one of the five essential pillars of religion. For those
with diabetes, Ramadan presents a metabolic challenge with potential health hazards of
hypoglycemia as well as hyperglycemia. With adequate preparation and planning, however,
most people with diabetes can experience, pleasant and satisfying fasting experience,
without any negative impact on health. In fact, fasting has been shown to have multiple
biopsychosocial health benefits.
This book humbly aims to help people with diabetes experience these benefits of Ramadan,
in a healthy manner. Through the evidence and experience, collated by contributors from
North America, Africa, and Asia, we hope to touch health care professionals across the globe.
These health care providers, in turn, should be able to help millions of people with
diabetes achieve the twin blessings of health and spiritual upliftment.
Abdul H Zargar
Sanjay Kalra
acknowledgments
We express our sincere gratitude to all the contributors for their efforts. Clinicians from
three continents have shared their knowledge to fill the void for a comprehensive book on
Ramadan and diabetes. Their enthusiasm and energy cannot be described in words.
We would like to sincerely thank M/s Jaypee Brothers Medical Publishers (P) Ltd, New
Delhi, India, for the opportunity to publish this title with them. A word of thanks for Dr
Neeraj Choudhary, Senior Medical Editor and Ms Madhvi Thakur, Editorial Coordinator, for all
the editorial support and for tirelessly working to bring out this book in its final shape and
form, in a very short span of time. The speed with which this book was coordinated across
countries is a testimonial to their efficiency and to the wonders of 24/7 collaboration that
technology has made possible.
Most of all, we thank our patients, who trust us with their health, and ask umpteen
questions regarding fasting in Ramadan, and motivated us to plan this book.
13
Contents
Section 1 overview
To Cure
Diabetes Click
Here
1. Overview
Sanjay Kalra
Health 3
Intrusion in Health 3
Ramadan 4
Biopsychosocial Model 4
Person Centered Care 4
The Role of the Physician 5
Newer Drugs and Technologies: The Knowledge Paradox
The Flow of this Book 6
2. Introduction
3. Pre-Ramadan Counseling
Altamash Shaikh
Goals of Counseling 12
Prerequisites 13
Awareness Revolutions/Campaigns 13
Ramadan Education and Role of the Health Care Providers
Counseling Strategies 14
Counseling Content for the Patients 15
Benefits of Pre-Ramadan Counseling 20
Conflict of Interest 21
12
13
4. Endocrinology of Fasting
22
39
14
Contents
Whom to Stratify?
40
Special Situation 44
Benefits of Risk Stratification
44
45
61
64
67
Sarita Bajaj
How the Fast is Observed 68
Diabetes and Fasting during Ramadan 68
The Physiological State of Diabetics During Ramadan 68
Effect of Fasting on Various Metabolic Parameters in Diabetics 69
Pre-Ramadan Considerations in Diabetics 70
Complications that Might be Associated with Fasting in Diabetics 71
Risk Stratification of Patients with Diabetes during Ramadan 73
Management of Diabetics during Ramadan 73
79
15
Contents
15
85
86
95
102
105
116
126
129
132
16
Contents
16
137
143
146
149
Sarita Bajaj
Pregnancy and Ramadan 150
Lactation and Ramadan 153
Sickness and Medication 153
156
157
165
17
Contents
169
17
174
178
180
183
Circulation, IV Access and Monitoring
185
184
188
195
Index
207
Section
Overview
CHAPTERS
1.
Overview
2.
Introduction
3.
Pre-Ramadan Counseling
4.
Endocrinology of Fasting
5.
6.
Chapter
1
Overview
Sanjay Kalra
Abstract
Successful completion of Ramadan is a great achievement for believers and provides spiritual merit.
Helping others in their achievement is equally meritorious. Through its chapters, this book tries to
facilitate the observance of healthy Ramadan fasting, for millions of Islamic adherents with diabetes.
This book is a sincere attempt to solve this paradoxical challenge for diabetes care professionals who
have to manage diabetics observing the Ramadan fast. It provides practical guidance regarding various
aspects of diabetes management during the holy month.
HEALTH
The most beloved by Allah of things He is asked to grant is (Al-aafiyah) good health
(Tirmidi).
Health is a state of a life that all living beings aim for: A condition of complete physical,
mental and social well-being, and not merely the absence of disease or infirmity.1
As physicians, we are privileged to be able to help our fellow human beings try and
achieve this state.
At times, however, our treatments and cures may end up being worse than the
disease or disorder itself. This sometimes happens because of side effects or adverse
reactions to our drugs. More often than not, however, patients complain of a high
index of intrusion of treatment. This is especially true for people with diabetes, who
have to deal with this chronic condition on long-term basis.
INTRUSION IN HEALTH
Intrusion of treatment, in this context, means a forced change in ones routine lifestyle,
caused by a particular management strategy. For example, being asked to take six
meals a day may be considered as intrusion by a person habituated to two major
Section 1: Overview
RAMADAN
O ye who believe! Fasting is prescribed to you as it was prescribed to those before you,
that ye may (Learn) self-restraint, (Al-Quran 2:183).
One such observance is Ramadan, the holy month of fasting, ordained as one of
the five central pillars of Islam. Followed by billions of adherents, spread across all
continents, the Ramadan fast provides spiritual upliftment and wellbeing to people
who practice the Islamic faith.2 Keeping the Ramadan fast, however, poses physical
challenges to all persons. These challenges are magnified in persons with diabetes,
whose metabolic milieu may not be geared to prolonged fasting.
Apart from the physical stress associated with fasting, however, people with
diabetes also face psychological and social obstacles during Ramadan. The overlap
of Ramadan and diabetes, in fact, becomes a perfect case for the study of the
biopsychosocial model of health, so elegantly coined by Unger in 1977.3
BIOPSYCHOSOCIAL MODEL
The biopsychosocial model was created to explain the various nonbiological
determinants which impact health.3
This model has stimulated debate about health and disease, and has been utilized
not only in psychiatry, but also in chronic disease such as diabetes.4 The biopsychosocial
model is required for an indepth understanding of the Islamic persons perspective on
Ramadan. One of the important aspects of any individual, while defining health, is
the need to be normal, feel normal, and appear normal. The concept of appearing
normal becomes even more important in close knit societies, where premium is laid
on homogeneity rather than exceptions.
In Ramadan, when social contacts between friends and family increase, the need
to appear normal increases. For the person with diabetes, normalcy includes the
ability to observe the holy fast, join in group prayers, and take part in festival meals.
Chapter 1: Overview
Section 1: Overview
REFERENCES
1. WHO definition of Health. [online] Available from http://www.who.int/about/definition/
en/print.html. [Accessed on 18 June 2013].
2. Bashir MI, Pathan M, Raza SA, et al. Role of oral hypoglycemic agents in the management
of type 2 diabetes mellitus during Ramadan. Indian J Endocr Metab. 2012;16:503-7.
3. Engel GL. The need for a new medical model: a challenge for biomedicine. Science.
1977;196(4286):129-36.
4. Adler RH. Engels biopsychosocial model is still relevant today. J Psychosom Res. 2009;
67 (6): 607-11.
5. Committee on Quality of Health Care in America: Institute of Medicine: Crossing the
Quality Chasm: A New Health System for the 21st Century. Washington, DC: The National
Academies Press; 2001.
6. Niazi AK, Kalra S. Patient centred care in diabetology: an Islamic perspective from South
Asia. J Diabetes Metab Disord. 2012;11:30.
7. Pathan M, Sahay RK, Zargar AH, et al. South Asian Consensus Guideline: Use of insulin in
diabetes during Ramadan. Indian J Endocr Metab. 2012;16:499-502.
8. Kalra S, Unnikrishnan AG, Skovlund SE. Patient empowerment in endocrinology. Indian J
Endocr Metab. 2012;16:1-3.
9. Jaleel MA, Raza SA, Fathima FN, et al. Ramadan and diabetes: As-Saum (The fasting).
Indian J Endocr Metab. 2011;15:268-73.
10. Pathan M, Sahay RK, Zargar AH, et al. South Asian Consensus Guideline: Use of GLP-1
analogue therapy in diabetes during Ramadan. Indian J Endocr Metab. 2012;16:525-7.
11. Bajwa SS, Kalra S. Logical empiricism in anesthesia: A step forward in modern day clinical
practice. J Anaesthesiol Clin Pharmacol. 2013;29:160-1.
Chapter
Introduction
Mahdi Kamoun, Mouna Feki Mnif, Ines Slim
Abstract
Health is the key to our happiness, and what we consume directly affects our health. Islam encourages
Muslims to ensure that they are mindful of their health. Fasting during the month of Ramadan is one
of five pillars of Islamic practices. During the Islamic fast, Muslims must refrain from smoking, eating,
drinking, sexual activity, consuming oral medications and using intravenous fluids. In addition, they
are encouraged to do more acts of piety, i.e. prayer, charity, or reading the Quran during this month.
Ramadan fasting induces favorable changes on metabolic parameters, reduces oxidative stress
and inflammation, promotes cardiovascular benefits, improves brain function and boots immunity.
However, Ramadan benefits require some careful considerations with an adequate pre-Ramadan
medical assessment and education as well as conservation of healthy dietary habits and adopting a
healthy lifestyle during and after the fasting period.
Health is the key to our happiness, and what we consume directly affects our health.
Islam encourages Muslims to ensure that they are mindful of their health. Holy
Prophet Muhammad (peace be upon him and his progeny) said: Take advantage of
the good health before illnesses afflict you. He also encouraged Muslims to try their
best to adopt a healthy living lifestyle that includes a healthy diet, regular mental and
physical exercise and a balance between spirituality and materialism.
Muslims comprise nearly a quarter of the worlds population with nearly 1.7
billion followers.1 Fasting during the month of Ramadan is one of five pillars of
Islamic practices, which also include the following: Shahadah, meaning faith in one
God and faith in the prophet (Muhammad, and all other prophets); Salah, meaning
five prayers a day; Zakah, meaning 2.5 percent annual capital gain deduction, taken
from the rich and given to the poor; Haj, meaning one pilgrims visit to Mecca in a
lifetime, whenever possible; and Ramadan fasting. Quran says O you who believe!
Fasting is prescribed for you, as it was prescribed for those who came before you; that
you will perhaps be God-fearing. (Al-Quran 2:183).
Section 1: Overview
Chapter 2: Introduction
Fasting is known in the Arabic language as Sawm and literally means abstention
from. During the Islamic fast, Muslims must refrain from smoking, eating, drinking,
sexual activity, consuming oral medications and using intravenous fluids. In addition,
they are encouraged to do more acts of piety, i.e. prayer, charity, or reading the Quran
during this month.
Fasting occurs in the 9th month of the Islamic calendar (Hijra) which is lunar
based. The Islamic calendar has 354 days thus precedes every year by 1011 days. The
period of fasting lasts from dawn to dusk. The meal consumed at dawn and dusk is
known in Arabic as Suhur and Iftar respectively.
Ramadan month can occur in any of the four seasons and the duration of restricted
food and beverage intake can vary from 1120 hours depending upon the exact time
of sunrise and sunset in each country or region. Over the coming years, the number
of fasting hours will progressively increase in the northern hemisphere as Ramadan
falls in the summer months. This will have important implications for Muslims with
chronic illnesses who wish to fast.
Fasting does not apply to all Muslims. If it is considered to be detrimental to an
individuals health then the Quran states fasting should be avoided: So everyone of
you who is present (at his home) during that month should spend it in fasting, but if
anyone is ill, or on a journey, the prescribed period (should be made up) by days later.
Allah intends every facility for you; He does not want to put to difficulties. (He wants
you) to complete the prescribed period, and to glorify Him in that He has guided you;
and perchance ye shall be grateful. (2:185).
Those exempted from fasting include:
The frail and elderly
Children (until they reach puberty)
Those who have a chronic condition whereby participating in fasting would be
detrimental to their health
Those who cannot understand the purpose of fasting, i.e. those who have learning
difficulties or those who suffer from severe mental health problems
Travelers (those traveling greater than 50 miles)
Those acutely unwell
Menstruating women
Pregnant and breastfeeding women.
Chapter 2, verse 184 of the Quran makes it explicitly clear that people who have
an illness or medical condition of any kind that makes fasting injurious to their health
are exempted from fasting. To compensate for the missed fasts, they must fast later
when they are healthy; if this is not possible due to long-term illness, they must feed
the poor.
Islamic fasting is different from other types of fasting:
As compared to other diet plans, in fasting during Ramadan, there is no
malnutrition or inadequate calorie intake since there is no restriction on the type
or amount of food intake during Iftar or Suhur
Fasting in Ramadan is voluntarily undertaken, as opposed to being a prescribed
imposition from a physician
In Islamic fasting, we are not subjected to a diet of selective food only (i.e. protein
only, fruits only, etc.).
Section 1: Overview
Chapter 2: Introduction
Additional prayers are prescribed after the dinner. These prayers constitute
appropriate level of physical activity (equivalent to moderate physical activity).
What is clear is that some patients with chronic illnesses insist on fasting even
though they are permitted not to by Islamic rules. The population-based Epidemiology
of Diabetes and Ramadan 1422/2001 (EPIDIAR) study demonstrated that among
12.243 people with diabetes from 13 Islamic countries, 43 percent of patients with
Type 1 diabetes and 79 percent of patients with Type 2 fast during Ramadan, lead to
the estimate that worldwide more than 50 million people with diabetes fast during
Ramadan.2
For many people, the key question regarding fasting is whether it is good or bad for
our health? The answer to this requires a quick overview of what happens inside the
body during fasting: the physiology of fasting.
Fasting triggers a complex array of neural, metabolic and hormonal adaptations
that maintain energy supply to the brain. Fasting state induces significant changes
in carbohydrate and lipid metabolism, favoring glycogenolysis, gluconeogenesis, and
lipolysis. Short-term fasting increases proteolysis and decreases protein synthesis.
However, as the duration of fasting increases, there are adaptive mechanisms
leading to preservation of lean mass; especially in obese subjects. Fasting leads also
to a fall in insulin and a rise in counter-regulatory hormones mainly glucagon and
catecholamines.
Muslims with diabetes, who wish to fast Ramadan are at risk of adverse events and
the risks may increase with longer fasting periods. Major risks associated with fasting
in patients with diabetes include:3
Hypoglycemia
Hyperglycemia
Diabetic ketoacidosis
Dehydration and thrombosis.
All patients with diabetes, who wish to fast during Ramadan should undergo a
medical assessment.3 They are categorized as at high, medium or low-risk of adverse
events during the fasting period. People with diabetes assessed to be at high-risk
are advised not to fast because they are much more likely to experience severe
hypoglycemic episodes and ketoacidosis. People at moderate risk should be educated
and supported before the start of Ramadan to make the necessary changes to reduce
and control their risks. Those assessed as being at low-risk should be able to fast
without health care supervision.
Prior to fasting, diabetics need to have appropriate education and treatment
adjustments and advice. The following principles of pre-Ramadan considerations
should be followed:
Assessment of the metabolic control
Adjustment of the diet protocol for Ramadan fasting
Adjustment of the drug regimen (e.g. changing long-acting hypoglycemic drugs to
short-acting drugs to prevent hypoglycemia)
Encouragement of continued appropriate physical activity
Recognition of warning symptoms of dehydration, hypoglycemia and other
possible complications.
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Section 1: Overview
Chapter 2: Introduction
10
1
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Section 1: Overview
Chapter 2: Introduction
11
ACknowledgmentS
We are thankful to Dr Basma Ben Naceur, Nadia Charfi, Fatma Mnif, Mohamed
Dammak, Nabila Rekik, Mohamed Habib Sfar, Larbi Chaieb, Mohamed Abid for their
contribution in the preparation of this manuscript.
ReFeRenCeS
1. Miller T. Mapping the Global Muslim Population: A Report on the Size and Distribution of
the Worlds Muslim Population. Washington, DC: Pew Research Center; 2009.
2. Salti I, Bnard E, Detournay B, et al. A population-based study of diabetes and its
characteristics during the fasting month of Ramadan in 13 countries: results of the
epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care
2004;27:2306-11.
3. Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes
during Ramadan: update 2010. Diabetes Care. 2010;33:1895-1902.
4. Casablance, Morracco. A Report on First International Congress Health and Ramadan
Foundation Hassan II, for Scientific and Medical Research on Ramadan, 1994.
Chapter
Pre-Ramadan Counseling
Altamash Shaikh
Abstract
Counseling and Ramadan-specific/structured education are the mainstay of success of safe fasting.
Adherence to optimal management of diabetes in Ramadan remains poor, hence, health care providers
must spend quality time in counseling patients. Understanding the local, social, cultural, economical,
and behavioral aspects of patients is integral in Ramadan-specific education. Mass awareness is vital
initial step towards this goal. All patients and their families be counseled regarding risks and rewards of
fasting. Warning symptoms and signs of emergency events must be explained. Counseling strategies,
content and benefits are discussed in this chapter.
INTRODUCTION
Awareness of Ramadan-specific education and its challenges have been into clinical
practice since the meeting in Casablanca on Ramadan and diabetes. Adherence to
optimal practices in the management of diabetes in Ramadan remains poor, despite
of the presently available treatment options, hence, health care providers must spend
quality time in counseling patients.
One study found that counseling before Ramadan was received by only about
one-third of patients. Education specific to Ramadan has profound beneficial effect
on fasting once patients received adequate counseling. However, irrespective of the
fasting in Ramadan, counseling forms the main backbone in the management of
diabetes, worldwide.
GOALS OF COUNSELING
Individualization of treatment
Eventless fasting, for patients willing to fast.
13
Section 1: Overview
13
PREREQUISITES
Patient centered approach needs to be implemented while addressing Ramadanspecific diabetes education. Counseling all the diabetic patients pre-Ramadan is a
must, whether they will be fasting or not.
Structured diabetes counseling before Ramadan includes educating patients,
health care providers, and patients families.
Provide counseling at least 812 weeks before Ramadan.
Provide adequate time for the patients and families to get ready for change in
lifestyle pattern during Ramadan. Use of local language is advocated for better
dispersion of counseling content.
Counseling has to be provided by the health care provider to the patient in
individual and/or can be done in groups. Patients should be clearly explained the risks
involved in fasting and concerns of preventable complications. Patients local, social,
cultural, economical and attitudinal beliefs must be kept in mind before counseling.
Then the changes in diet or treatment regimen should be started, so that patients
welcome Ramadan fast on a stable and accepted treatment regimen.
Training of medical personnel in counseling is of paramount importance in areas
of high illiteracy and for the regions with poor resources and the underprivileged.
Most important part of counseling the diabetic patients for Ramadan is that each
aspect has to be highly individualized.
AWARENESS REVOLUTIONS/CAMPAIGNS
The step in Ramadan focused/specific diabetes education is revolutionary campaigns
to create awareness among general public, health care providers and patients. This
can be done in various ways, through hospital notices or other medias. Patients feel
beatitude during Ramadan and worship more in this holy month. Awareness through
religious leaders by meeting lmams in the mosques and letting them to talk to general
public is successful way of spreading education about diabetes.1
14
Section 1: Overview
14
COUNSELING STRATEGIES
These can be of the following types:
Individual Counseling
Like individualized treatment, face to face counseling gives opportunity for the
patients to talk to their health care providers. Understanding the problems on a
individual basis by a particular patient in Ramadan, impacts and enhances outcomes
of counseling.
Group/Peer Counseling
This may be effective at a local level where a group or large masses may be able to
gather, and then counseled. Such session may be of one to two hours sessions.
Physician, religious leaders may take a role in addressing groups (Table 1).
Table 1: Preparing for counseling
Patient centered approach, highly individualized counseling
Provide counseling 812 weeks before Ramadan
Consider local, social, cultural, economical attitudinal beliefs and literacy levels
Ramadan comes in various seasons and climatic conditions
Provide Ramadan-specific/structured diabetes education
Spreading awareness through medical personnel or religious leaders
Adjustment of prescription for diabetes related and unrelated medicines
15
Section 1: Overview
15
Family Counseling
For patients who want to fast and are also dependent on their family members for
treatment and daily routine, would require family counseling. Nonetheless, in
Type 1 diabetics, desirous of fasting family is involved in economical, emotional and
technical ways. Educating all in the family, reducing their exaggerated anxiety and
fears is prudent in such cases.
Pre-Ramadan Check
Patients should be educated about the importance of pre-Ramadan clinical evaluation
inclusive of; clinical profile, biochemistry, appropriate comorbidities assessment.
It should begin at least 23 months in advance. This medical assessment should
include a minimum of complete physical examination, an assessment of metabolic
control, and laboratory tests (inclusive of but not limited to: fasting and postprandial
glucose, lipid profile, urine acetone, glycated hemoglobin, spot urine microalbumin,
creatinine, self-monitoring of blood glucose). Few patients may need more detailed
evaluation depending on their current control and complication.
Fasting Risks
The four major risks involved in fasting are:
1. Hypoglycemia.
2. Hyperglycemia.
3. Diabetic ketoacidosis.
4. Dehydration and thrombosis.
Warning symptoms of hypoglycemia must be told to every patient, so as to
recognize hypoglycemia in a very early stage and prevent catastrophes.
Feeding Roster
Planning of sunrise meal (Suhur) and sunset meal (Iftar), reinforce adherence to
regular dietary habits and refrain from delicious indulgence. Individualization of
diet is vital considering patients local customs and associated risk factors. Thus, the
16
Section 1: Overview
16
dietary prescription should take into account the nutritional needs, metabolic milieu,
concurrent comorbidities, social scenario and pocket potency of the patients.
At the sunrise meal (Suhur), preparations with slowly digesting and absorbing
properties like complex carbohydrates are preferable, including slow energy releasing
foods (e.g. made of wheat or rice or beans) depending on their staple food. Patients
may be also advised to have their Suhur, just before the time of start of fasting hours,
instead of eating late night and sleeping without getting up for sunrise meal (Suhur).
At sunset meal (Iftar), patients should eat diet composed of simple carbohydrates.
Avoid sweets or dense sugary (halwas, firnis, malpuas) food items. Avoid large meals,
fatty meals (bhajias, samosas, crispies). Discourage overeating/binging.
Some patients may do well with daily dietary and weight recordings, and selfassessing on the pattern and quantum of intake. This should be supervised by the
health care provider.
Change in weight of more than 23 kilograms should prompt evaluation in these
patients.
Inappropriate diet, untimely eating patterns are the most common reasons for
health issues in diabetic patients in Ramadan.
Thus, health care providers must provide guidance on food feasibility and avoid
feasting by patients.
17
Section 1: Overview
17
to three smaller meals, besides scheduled physical activity in the postsunset meal
(Iftar) period helps prevent hyperglycemia.
18
Section 1: Overview
18
Hyperglycemia
With sudden decrease in insulin doses just prior to Ramadan, in Type 1 diabetes
has more chances of hyperglycemia with impending diabetic ketoacidosis. Patients
should avoid doing such self-dosages. Thus, the health care provider has to discuss
not only about the dosages and checks but also counsel against gulping of food or
skipping of meals or heavy meals to avoid after effects of hyperglycemia. Change in
individual attitude towards diabetes is important determinant for successful fasting.5
Prompt Rehydration
Apart from hypoglycemia, another immense preventable issue is dehydration.
Diabetic patients should be counseled to take fluids adequately in between sunset
meal (Iftar) and sunrise meal (Suhur), i.e. nonfasting hours.
Intake of water should be supervised by patients themselves and family members.
This avoids dehydration, electrolyte imbalance, thrombosis especially in hot climatic
conditions and long hours of fasting.
Worsening of hypercoagulable state and the subsequent risk, is due to
intravascular contraction and then increased viscosity of blood. Hence, in some
patients antiplatelets may be considered. This is integral in areas where fasting hours
are prolonged 1820 hours.
Exercise Regimen
Daily physical activity/routine can be maintained in Ramadan. Both resistance and
aerobic exercise can be done in Ramadan depending upon the comorbidities. Utmost
care to be taken to avoid hypoglycemia.
Avoid exercise prior to sunset meal (Iftar). It may be done postsunset meal (Iftar),
post-Isha prayers or in some postmidnight Tahajjud prayers.
Walking and stationary cycling may be good options when performed. Avoid
exercise in the late hours of fasting prior to sunset meal (Iftar).
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Section 1: Overview
19
This must be discouraged at all levels, and patients have to be counseled to revert to
nonfasting state and avoid any such temptation. Thus, in any diabetic patients with
glucose value of < 60 mg/dL (3.3 mmol/L) fast must be broken immediately, and
treatment be sought, as no human can vouch for further decline in glucose levels.
When blood glucose values are < 70 mg/dL (3.9 mmol/L) in the early hours postsunrise meal (Suhur), then also fast should be broken in patients oral (sulfonylurea,
meglitinide ) or insulin taken at Suhur.
Avoidance of fasting on sick days. Avoidance with hyperglycemia blood glucose
more than 300 mg/dL (16.7 mmol/L).
Risk Stratification
Patients may be divided into four risk categories, based on clinical expertise and
experience namely: very high risk, high risk, moderate risk and low risk. (The reader is
directed to chapter on risk stratification for details.)
20
Section 1: Overview
20
Warning Signs
Any slightest symptoms or signs of hypoglycemia or hyperglycemia or dehydration
should be immediately taken care off. They should be advised to immediately treat the
hypoglycemia and/or seek for medical help in cases of severe cases.
Team Work
Patients, family members, health care providers (doctors from various specialties,
nutritionists, counselors) and local Islamic scholar when required. This may even be
needed during and post-Ramadan, for successful future fruition.
SUMMARY
In order to have an effective counseling it is necessary to understand patients lifestyle
during Ramadan, to avoid any dissociation between patients and health care provider
(Table 3).
Lifestyle modification, dietary adjustment, treatment adherence are cornerstone
of successful Ramadan fasting.
21
Section 1: Overview
21
Glycemic stability must be achieved in all patients, who are conscious of their
fasting and compliance must be assured, directly or indirectly through patients or
families. All patients must be explained warning signs of complications. Counseling
has contributed lots in diabetes management and also benefits in Ramadan.
CONFLICT OF INTEREST
None.
REFERENCES
1. Khan AK. Diabetes awareness through religious leaders. Indian J Endocrinol Metab.
2013;17(1):178-9.
2. Abir Zakaria, Inas Sabry AE. Ramadan-like fasting reduces carbonyl stress and improves
glycemic control in insulin treated Type 2 diabetes mellitus patients. Life Science Journal.
2013;10(2):384-90.
3. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ)
programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabetic medicine: a
journal of the British Diabetic Association [Online]. 2013;27(3):327-31. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/20536496. [Accessed March, 2013].
4. Salti I, Benard E, Detournay B, et al. A Population-based study of diabetes and its
characteristics during the fasting month of Ramadan in 13 countries. Diabetes Care.
2004;27(10):2306-11.
5. Fatim J, Karoli R, Chandra A, et al. Attitudinal determinants of fasting in Type 2 diabetes
mellitus patients during Ramadan. The Journal of the Association of Physicians of India
[Online]. 2011;59:630-4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22479742.
[Accessed June 2013].
6. Shaikh A. Family therapy in diabetes mellitus. IJEM. 2013;238:13 (in press).
7. Kalra S, Sridhar G R, Balhara YS, et al. National recommendations: Psychosocial
management of diabetes in India. Indian J Endocr Metab 2013;17:376-95.
Chapter
Endocrinology of Fasting
Ines Slim, Mahdi Kamoun, Mouna Feki Mnif
Abstract
Fasting during Ramadan is a religious duty for all healthy adult Muslims and implies abstention
from food and drink from dawn to sunset. Fasting triggers a complex array of neural, metabolic and
hormonal adaptations that maintain energy supply to the brain. Fasting state induces significant
changes in carbohydrate and lipid metabolism, favoring glycogenolysis, gluconeogenesis and lipolysis.
Short-term fasting increases proteolysis and decreases protein synthesis. However, as the duration of
fasting increases, there are adaptive mechanisms leading to preservation of lean mass; especially in
obese subjects. Fasting leads also to a fall in insulin and a rise in counter-regulatory hormones mainly
glucagon. Prolonged fasting is a strong physiological stimulus equivalent to a biological stress that
activates the hypothalamic-pituitary-adrenal (HPA) axis. However and during Ramadan fasting, some
brains cellular mechanisms of stress resistance are activated to protect neurons from the deleterious
effects of this HPA axis activation. These metabolic and hormonal mechanisms of adaptation to fasting could be altered in patients with diabetes mellitus who are continuing to fast despite the advice
of their doctors to not.
We review in this chapter the current understanding of the physiopathology of short-term fasting
especially during Ramadan and its metabolic and hormonal effect in healthy subjects and in patients
with diabetes mellitus.
INTRODUCTION
23
Section 1: Overview
23
24
Section 1: Overview
24
estimated prevalence of fasting during Ramadan was 43 percent for Type 1 DM and
86 percent for Type 2 DM.4
Furthermore, the time of onset of Ramadan is based on the lunar calendar which
is different from the most commonly used international civil calendar (Gregorian
calendar). Subsequently, the duration of daily fast and the overall period of the month
of Ramadan vary each year depending on the geographical location and season.
During summer, such as this year, in temperate regions and northern latitudes, the
fast may last up to 18 hours per day. This variability of the length of daylight, and
therefore the length of fasting, has considerable consequences especially for a person
living with diabetes; and makes fasting more challenging physically, mentally and
emotionally.
Nevertheless, as Ramadan is perceived by Muslims as a period for self-purification,
self-discipline, austerity and charity, as a time of worship and contemplation and as
an opportunity to strengthen family and community ties,5 all these perceptions might
provide a soothing sensation and well-being that can make patients more receptive
for therapeutic education. It could be considered as an excellent opportunity to
motivate and empower patients to be more observant to their treatment, to accept
insulin therapy in order to improve their glycemic control and to enhance the selfmanagement of the disease. It is also an opportunity to stop smoking.
Understanding the benefits and limitations of fasting and following the right
nutritional guidelines will help fasts to live better this month.
25
Section 1: Overview
25
Effects
Carbohydrate
Lipids
Caloric intake
Body weight
Liver
Kidneys
Hematological profile
Neuropsychiatric
Endocrine glands
None
degree
of
26
Section 1: Overview
26
as possible explanations of this sex difference. Women are also known to become
ketotic more rapidly than men during fasting, and ketosis appears to decrease
gluconeogenesis, thereby indirectly affecting plasma glucose levels.1
During longer fasting days of more than 16 hours often associated with heavy
compensatory meals, the hepatic stores of glycogen (providing about 75% of glucose
requirements), along with some degree of gluconeogenesis (coming from precursor
acids, lactate, pyruvate and glycerol) maintain serum glucose levels within normal
limits.
Although, humans cannot synthesize glucose directly from fat, the energy derived
from oxidation of free fatty acids facilitates hepatic glucose synthesis from lactate and
glycerol.1
As a consequence, serum glucose level during Ramadan fasting is very variable. It
may decrease slightly in the first few days of Ramadan with minimal level reported at
63 mg/dL, normalizing by the 20th day and showing a slight rise by the 29th day.14
27
Section 1: Overview
27
28
Section 1: Overview
28
lactate, pyruvate, amino acids and glycerol. In this process, cortisol is the principal
stimulus for the catabolism of muscle protein. Simultaneously the decrease in insulin
and rise in catecholamine production results in lipolysis in the adipose tissue and a
rise in the level of free fatty acids, which replaces glucose as the essential fuel for use
by other tissues of the body.1,14
Growth hormone (GH) plays a key role in protein, carbohydrate and fat metabolism.
It also has known lipolytic effects21 and may be diabetogenic in large doses or in
smaller amounts in the absence of insulin.22 Its secretion fluctuates widely during the
day with a major increase during early sleep.22 Prolonged fasting is known to enhance
progressively GH secretion in addition to other known stimuli such as hypoglycemia,
exercise, certain amino acids, catecholamines, stress and certain drugs (for example,
L-dopa, vasopressin).1
The effect of fasting on GH secretion appears to vary among obese and nonobese
subjects.1
It is also apparent from several studies that glucose homeostasis during fasting is
dependent in part on the presence of GH.1,23
29
Section 1: Overview
29
Figure 2: Patterns of some hormones on the control day (before Ramadan) and on the 23rd day of Ramadan. Each time point is the mean and SEM of 10 subjects. Cortisol rhythm showed biphasic pattern, with a
rise in serum levels in the afternoon. Melatonin maintained its circadian rhythmicity during Ramadan. The
circadian rhythm of serum TSH was also preserved, but its amplitude was flattened during Ramadan. There
was delayed the onset of the increase of testosterone during Ramadan. Prolactin showed an increased evening peak. There were no significant changes in the 24-hour mean concentrations of the measured hormones
except for melatonin which reduced significantly and FSH which showed significant but slight decrease.25
Abbreviations: SEMStandard eroor of the mean; TSHThyroid-stimulating hormone
30
Section 1: Overview
30
expected in primary thyroid dysfunction. Azizi29 has already shown that basal TSH
concentrations may decrease in short-term fasting or remain unchanged in prolonged
fasting (more than three weeks). In addition, TSH response to thyrotropin-releasing
hormone (TRH) infusions may be blunted29 or unchanged.30
In Islamic fasting, no alterations in serum concentrations of testosterone,
gonadotropins and prolactin have been detected in normal males; though a slight
decrease in FSH levels was reported in one study.24 In prolonged fasting, serum LH
response to GnRH infusion is typically normal, but serum FSH response to GnRH may
be blunted during fasting.31
Ramadan fasting did not result in significant change in serum concentration of
parathyroid hormone (PTH). Mean serum concentrations of calcium may decrease
slightly 10-day after the beginning of fasting; however, no subnormal values can be
seen.32
31
Section 1: Overview
31
32
Section 1: Overview
32
33
Section 1: Overview
33
with Type 2 DM (Table 2).4 No episodes of diabetic ketoacidosis (DKA) have been
reported in small studies including fasting patients with T1 DM treated by insulin
analogs or insulin pump therapy.53-55
In a multicenter observational study (n = 1374), symptomatic hypoglycemia
occurred in about 20 percent of diabetic patients on sulfonylurea with or without
metformin who fast during Ramadan,55,56 whilst other studies have not shown a
significant increase in the risk of hypoglycemia during Ramadan in patients treated
with oral diabetic medications or insulin57,58
A recent review about glycemic emergencies identified several risk factors for
DKA associated with fasting during Ramadan such as: patients with T1DM; excessive
reduction of insulin dosages based on the assumption that food intake is reduces
during this month so that they prevent hypoglycemia; patients with hypercoagulation
state; moderate to severe hyperglycemia before fast, renal insufficiency, advanced
micro and macrovascular complications; dose reduction during infection that cannot
be able to meet sufficiently the stress demanded induced by raised catecholamines
and steroids.59
34
Section 1: Overview
34
During
Ramadan
Type 2 diabetes
P
Value
Before
Ramadan
During
Ramadan
P
Value
Overall population
Severe hypoglycemia
0.03 0.1
Severe hyperglycemia/
ketoacidosis
0.14 0.6
0.02 0.05 0.12 0.48 0.9896 0.003 0.02 0.02 0.22 0.0034
Severe hyperglycemia/
ketoacidosis
0.05 0.08 0.15 0.51 0.6701 0.009 0.04 0.04 0.30 0.0015
35
Section 1: Overview
35
CONCLUSION
Metabolic and hormonal changes generally support the safety of fasting in Ramadan
for most diabetic patients: no worsening of diabetic control and no significant
change in metabolic parameters were observed. Nevertheless, patients who choose
to fast should be deliberately advised to modify their treatment during Ramadan.
Subsequently, the patient should be encouraged to have appropriate pre-Ramadan
assessment and education in order to stratify and modify his or her risk with fasting.
Dose and timing adjustments to insulin and to some oral hypoglycemic agents,
especially sulfonylureas, may well be necessary during Ramadan (cf. chapter 12:
Incretin-based therapies and fasting during Ramadan).
Conflict of interest: none to declare.
ACKNOWLEDGMENTS
We are thankful to Dr Nadia Charfi, Nabila Rekik, Koussay Ach, Molka Chadli Chaieb,
Amel Maaroufi, Maha Kacem, Mohamed Abid, Larbi Chaieb for their contribution in
the preparation of this manuscript.
REFERENCES
1. Kerndt PR, Naughton JL, Driscoll CE, et al. Fasting: the history, pathophysiology and
complications. West J Med. 1982;137:379-99.
2. Kassab S, Abdul-Ghaffar T, Nagalla DS, et al. Interactions between leptin, neuropeptide-Y
and insulin with chronic diurnal fasting during Ramadan. Ann Saudi Med. 2004;24:345-9.
36
Section 1: Overview
36
3. Arbesman R. Fasting and prophecy in pagan and Christian antiquity. Tradition 1951;7:1-71.
4. Salti I, Bnard E, Detournay B, et al. A population-based study of diabetes and its
characteristics during the fasting month of Ramadan in 13 countries: results of the
epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care.
2004;27:2306-11.
5. Awad AK. Fasting in Ramadan according to the Quran and Sunnah. [online] Available
from website ILoveAllaah.com. [Accessed 2012].
6. Felig P. Starvation. In Endocrinology De Groot LJ, (Ed). New York: Grune & Stratton; 1979.
pp. 1927-40.
7. Azizi F. Islamic fasting and health. Ann Nutr Metab. 2010;56:273-82.
8. Vasan SK, Mahendri NV, Arulappan N, et al. A prospective assessment of dietary patterns
in Muslim subjects with type 2 diabetes who undertake fasting during Ramadan. Indian J
Endocrinol Metab. 2012;16:552-7.
9. Cahill Jr GF. Starvation in man. Clin Endocrinol. Metab 1976;5:397-415.
10. Cahill GF, Herrera MG, Morgan AP, et al. Hormone-fuel interrelationships during fasting. J
Clin Invest. 1966;45:1751-69.
11. Merimee TJ, Tyson JE. Stabilization of plasma glucose during fasting; Normal variations in
two separate studies. N Engl J Med. 1974;291:1275-8.
12. Merimee TJ, Fineberg SE. Homeostasis during fasting. II. Hormone substrate differences
between men and women. J Clin Endocrinol Metab. 1973;37:698-702.
13. Tyson JE, Farinholt J. Estrogen modulation of glucose homeostasis. Clin Res. 1974;22:481A.
14. Azizi F. Research in Islamic fasting and health. Ann Saudi Med. 2002;22:186-91.
15. Saudek CD, Felig P. The metabolic events of starvation. Am J Med. 1976;60:117-26.
16. Cahill GJ, Owen OE, Morgan AP. The consumption of fuels during prolonged starvation.
Adv Enzyme Regul. 1968;6:143-50.
17. Reilly T, Waterhouse J. Altered sleep-wake cycles and food intake: the Ramadan model.
Physiol Behav. 2007;90:219-28.
18. Afolabi PR, Jahoor F, Jackson AA, et al. The effect of total starvation and very low energy
diet in lean men on kinetics of whole body protein and five hepatic secretory proteins. Am
J Physiol Endocrinol Metab. 2007;293:E1580-9.
19. Welle S, Statt M, Barnard R, et al. Differential effect of insulin on whole-body proteolysis and
glucose metabolism in normal-weight, obese, and reduced-obese women. Metabolism.
1994;43:441-5.
20. Sapir DG, Owen OE. Renal conservation of ketone bodies during starvation. Metabolism.
1975;24:23-33.
21. Raben MS, Hollenberg CH. Effect of growth hormone on plasma fatty acids. J Clin Invest.
1959;28:484-8.
22. Williams RH. Textbook of Endocrinology, 5th edn, Philadelphia: WB Saunders; 1974.
23. Felig P, Marliss EB, Cahill GF. Metabolic response to human growth hormone during
prolonged starvation. J Clin Invest. 1971;50:411-21.
24. Karamat MA, Syed A, Hanif W. Review of diabetes management and guidelines during
Ramadan. J R Soc Med. 2010;103:139-47.
25. Bogdan A, Bouchareb B, Touitou Y. Ramadan fasting alters endocrine and neuroendocrine
circadian patterns. Meal-time as a synchronizer in humans? Life Sci. 2001;68:1607-15.
26. Bahammam A. Effect of fasting during Ramadan on sleep architecture, daytime sleepiness
and sleep pattern. Sleep and Biological Rhythms. 2004;2:135-43.
27. Ben Salem L, Bchir S, Bchir F, et al. Circadian rhythm of cortisol and its responsiveness to
ACTH during Ramadan. Ann Endocrinol. 2002;63:497-501. (Article in French).
28. Heemstra KA, Soeters MR, Fliers E, et al. Type 2 iodothyronine deiodinase in skeletal
muscle: effects of hypothyroidism and fasting. J Clin Endocrinol Metab. 2009;94:2144-50.
37
Section 1: Overview
37
38
Section 1: Overview
38
51. Belkhadir J, el Ghomari H, Klcker N, et al. Muslims with non-insulin dependent diabetes
fasting during Ramadan: treatment with glibenclamide. BMJ. 1993;307:292-5.
52. Sari R, Balci MK, Akbas SH, et al. The effects of diet, sulfonylurea, and Repaglinide therapy
on clinical and metabolic parameters in type 2 diabetic patients during Ramadan. Endocr
Res. 2004;30:169-77.
53. Azar ST, Khairallah WG, Merheb MT, et al. Insulin therapy during Ramadan fast for patients
with type 1 diabetes mellitus. J Med Liban. 2008;56:46.
54. Kadiri A, Al-Nakhi A, El-Ghazali S, et al. Treatment of type 1 diabetes with insulin lispro
during Ramadan. Diabetes Metab. 2001;27:482-6.
55. Khalil AB, Beshyah SA, Abu Awad SM, et al. Ramadan fasting in diabetes patients on
insulin pump therapy augmented by continuous glucose monitoring: an observational
real-life study. Diabetes Technol Ther. 2012;14:813-8.
56. Aravind SR, Al Tayeb K, Ismail SB, et al. Hypoglycaemia in sulphonylurea-treated subjects
with type 2 diabetes undergoing Ramadan fasting: a five-country observational study.
Curr Med Res Opin. 2011;27:1237-42.
57. Bakiner O, Ertorer ME, Bozkirli E, et al. Repaglinide plus single-dose insulin glargine: a
safe regimen for low-risk type 2 diabetic patients who insist on fasting in Ramadan. Acta
Diabetol. 2009;46:63-5.
58. Cesur M, Corapcioglu D, Gursoy A, et al. A comparison of glycemic effects of glimepiride,
repaglinide, and insulin glargine in type 2 diabetes mellitus during Ramadan fasting.
Diabetes Res Clin Pract. 2007;75:141-47.
59. Ahmad J, Pathan MF, Jaleel MA, et al. Diabetic emergencies including hypoglycemia
during Ramadan. Indian J Endocrinol Metab. 2012;16:512-5.
60. Ahmedani MY, Haque MS, Basit A, et al. Ramadan prospective diabetes study: the role
of drug dosage and timing alteration, active glucose monitoring and patient education.
Diabet Med. 2012;29:709-15.
61. Hui E, Oliver N. Low glycaemic variability in subjects with Type 2 diabetes following
pre-Ramadan assessment and adjustments for fasting. Diabet Med. 2012;29:828-9.
62. Al Suwaidi J, Bener A, Suliman A, et al. A population based study of Ramadan fasting and
acute coronary syndromes. Heart. 2004;90:695-6.
63. Bener A, Hamad A, Fares A, et al. Is there any effect of Ramadan fasting on stroke incidence?
Singapore Med J. 2006;47:404-8.
64. Alkandari JR, Maughan RJ, Roky R, et al. The implications of Ramadan fasting for human
health and well-being. J Sports Sci. 2012;30(Suppl 1):S9-19.
Chapter
5
Risk Stratification of
People with Diabetes
Altamash Shaikh
Abstract
It is a challenge to the treating health care professional to understand and implement the treatment
of diabetes in Ramadan so that it allows the patients to fast, without any disease-related or iatrogenic
complications. Stratifying the patients has benefits in both ways to patients and physicians. Events
can be minimized and complications prevented, with proper implementation of treatment and risk
stratification. Clinical profile, disease complications, expertise and experience have led to the following
categories: very high, high, moderate and low-risk. This chapter deals with various aspects and levels
of risk encountered in diabetes in Ramadan.
INTRODUCTION
Ramadan is a month of fasting where Muslims all over the world fast, however,
diabetic patients are exempt from fasting. But some patients insist to do so. It becomes
a challenge to the treating health care professional to understand and implement
the treatment of diabetes in such a way that it allows the fast to happen without any
disease-related or iatrogenic complications. This chapter deals with the prioritizing
the diabetic patients, at different risk levels based on various clinical factors, and how
to solve them in an efficient manner.
WHY STRATIFY?
Although diabetic patients themselves know to some extent the changes involved in
his/her daily routine during Ramadan, as health care professional we should do this
in a systematic and simpler way.
Bringing down the dangers of disease or its complications stands the first in the list
when we try to do this.
The recent EPIDIAR1 study revealed that the risk may be high in some diabetes
patients. Thus, it is necessary to stratify patients into various risk categories which will
40
40
HOW TO STRATIFY?
Although, there is lack of statistical figures and data from clinical or pharmacological
studies, expert consensus is available for risk stratification. Depending on the patients
clinical profile and the propensity of complications, patients can be grouped into the
following categories,3 inclusive of both Type 1 and Type 2 diabetes mellitus:
Very high
High
Moderate
Low-risk.
WHOM TO STRATIFY?
Let us see these various levels of risk stratification.
Very High-Risk
Depending on the activity levels, acuteness of problem, actual glucose levels,
autoimmunity in diabetes the following patients fall into very high-risk group.
41
41
Hypoglycemia
Hypoglycemia when requires third party assistance is severe, and can be prevented by
stratification and proper counseling. In the EPIDIAR study, hypoglycemia was seen
7.5 times more in Type 2 diabetes and those with significant sudden lifestyle changes.
Also, extreme changes in oral or insulin regimen just before Ramadan was a risk factor
(see chapter on counseling the patient before Ramadan for details). Patients with
hypoglycemia unawareness may be at the greatest risk for further complications. The
following patients are high-risk group due to hypoglycemia:
Severe hypoglycemia within the 3 months prior to Ramadan
A history of recurrent hypoglycemia
Hypoglycemia unawareness.
Hyperglycemia
High blood glucose or a episode of hyperosmolar hyperglycemic coma in the previous
3 months is detrimental to health for the patients willing to fast. Too much reduction
in current treatment dosages of diabetes medication can lead in a hyperglycemic
excursion. In the EPIDIAR study, hyperglycemia was 5 times more common in Type 2
diabetes. In clinical practice, it is observed that patients who indulge in large meals or
sugary food items are known to have hyperglycemia and or diabetic ketoacidosis. The
following are very high-risk group patients due to hyperglycemia:
Sustained poor glycemic control
Ketoacidosis within 3 months prior to Ramadan
Hyperosmolar hyperglycemic coma within the previous 3 months.
Activity Levels
Patients doing labor work or hard work while fasting are at increased risk of
dehydration and or thrombosis and need extra fluids to surmount these risks (See
chapter on exercise and Ramadan for detail).
Acute Illness
It is advisable always for patients in this group to avoid fasting.4 However, medical
conditions with acute illness in this group are:
Acute peptic ulcer
Severe bronchial asthma, pulmonary tuberculosis
Cancer
Overt cardiovascular diseasesrecent MI or sustained angina
Hepatic dysfunction
Severe infections.
Chronic Dialysis
Diabetic patients with established chronic kidney disease and on regular maintenance
hemodialysis are at increased risk of plasma glucose level fluctuation, and hence are
categorized into this risk group.
42
42
High-Risk
Earlier moderate hyperglycemia (average blood glucose 150300 mg/dL or A1C 7.59.0
percent) was considered as high-risk stratified group for fasting in Ramadan, however
with changes in availabilities in treatment modalities, this may not be so. Also, with
control and better management of their comorbid conditions the additional risk
factors may be reduced, thus further reducing the risk while fasting.
The following are stratified as high-risk group, mainly depending on presence of
complications, modality of treatment and age of the patients:
43
43
Moderate Risk
Diabetes patients treated with oral drugs like repaglinide or nateglinide which are
short-acting and are well-controlled, generally have good glycemic stability. But if
proper counseling is not done and advise not adhered they may be at moderate risk
for complications.
Low-Risk
Diabetes patients who are well-controlled with lifestyle modification, and drugs with
very low-risk of glycemic excursions like metformin, acarbose, thiazolidinediones,
44
44
and/or incretin-based therapies (DPP4 inhibitors and GLP1 analogs) and also are
otherwise healthy, have a low-risk when stratified for fasting in Ramadan.
SPECIAL SITUATION
Pregnancy and Lactation
Ladies with pregnancy or lactation may insist on fasting. Some group considers them
in very high-risk group but some may not consider this so. (See chapter on Insulin in
Type 2 diabetes for details).
SUMMARY
All diabetic patients need specialized and individualized care when fasting in
Ramadan. This can be identified by prioritization and categorization of patients into
various risk. Type 1 diabetics, elderly, autonomic neuropathy may present problems
but can be tackled with setting the targets and family involvement. Table 2 gives a list
of factors that put the patient to high-risk of complications during the fasting period.
Nearly every event can be minimized and complications prevented with proper
implementation of treatment and risk stratification.
REFERENCES
1. Salti I, Benard E, Detournay B, et al. A population-based study of diabetes and its
characteristics during the fasting month of Ramadan in 13 countries. Diabetes Care.
2004;27(10):2306-11.
2. Kalra S, Balhara YP, Bantwal G, et al. National recommendations: Psychosocial
management of diabetes in India. [online] IJEM. 2013;17(3):376. Available from: http://
www.ijem.in/text.asp?2013/17/3/376/111608. [Accessed June, 2013].
3. Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes
during Ramadan: update 2010. Diabetes care [online]. 2013;33(8):1895-902. Available
from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2909082&tool=pmce
ntrez&rendertype=abstract. [Accessed June, 2013].
4. Pathan MF, Sahay RK, Zargar AH, et al. South Asian Consensus Guideline: Use of insulin
in diabetes during Ramadan. [online] IJEM. 2013;16(4):499-502. Available from: http://
www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3401743&tool=pmcentrez&render
type=abstract. [Accessed June, 2013].
5. Shaikh A. Family Therapy in Diabetes Mellitus. IJEM. 2013;238:13 (in press).
Chapter
Abstract
Numerous epidemiologic studies showed positive effects of Ramadan fasting on various parameters in
diabetic and healthy subjects. Ramadan fasting induces favorable changes on metabolic parameters,
reduces oxidative stress and inflammation, promotes cardiovascular benefits, improves brain function
and boots immunity. Additionally, there is growing evidence that Ramadan fasting may have an anticancer role. It has also several spiritual, social and psychological benefits. Ramadan fasting would be
an ideal recommendation for treatment of some metabolic and inflammatory diseases. It should be
noted however that Ramadan benefits require some careful considerations such as necessity of an
adequate pre-Ramadan medical assessment and education as well as conservation of a healthy dietary
habits and adopting a healthy lifestyle. This paper summarizes current knowledge of beneficial effects
of Ramadan fasting in diabetic and healthy subjects.
INTRODUCTION
46
Section 1: Overview
Chapter 6: Beneficial Effects of Ramadan Fasting on Health
46
Glycemic Control
In properly educated, well-informed and motivated persons with diabetes, under
good medical supervision, no significant aberrations in their blood glucose values
were reported during Ramadan fasting. Ramadan can also lead to a reduction in
serum fructosamine and HbA1c levels in Type 2 diabetic patients.6-8 In a recent study,
systematic pre-Ramadan assessment with appropriate therapeutic adjustments and
educational advice was associated with low glycemic variability in Type 2 diabetic
subjects during Ramadan.9 However, it should be noted that Ramadan fasting can
lead to further deterioration in glycemic control in patients with previously poor
control.10
Anthropometric Parameters
A review of the literature shows a controversy about weight changes in diabetic
patients during Ramadan. Many studies reported a significant reduction in Type 2
diabetic patients weight during Ramadan.10,11 Some reports have shown no change
or even a slight increase in weight of these patients.12 Such discrepancies could be
explained by the variations in lifestyle factors particularly those related to food intake
and physical activity.10,11
47
Section 1: Overview
Chapter 6: Beneficial Effects of Ramadan Fasting on Health
47
Lipid Profile
Several studies among patients with Type 2 diabetes mellitus reported decreased total
cholesterol (TC), triglyceride (TG), very-low-density lipoprotein cholesterol (VLDL-C)
and low-density lipoprotein cholesterol (LDL-C) as well as increased high-density
lipoprotein cholesterol (HDL-C) levels after fasting in Ramadan.15 The changes in
lipid profile, however, may vary depending on the quality and quantity of food intake,
and physical activity.16
48
Section 1: Overview
Chapter 6: Beneficial Effects of Ramadan Fasting on Health
48
has been reported in different studies, the loss being greater in overweight persons.20
Ramadan fasting could also induce a decrease in body fat percentage and waist
circumference.18 Interestingly, weight loss was reported even without any reduction
in the total daily energy intake.18
Favorable effects of Ramadan fasting on different anthropometric parameters
could be explained by the regulatory mechanisms that the body activates during
fasting such as insulin hyposecretion and increased glucagon. These mechanisms
favor a predominant lipolytic state, with a higher tendency to utilize fat rather than
glucose as a source of energy, and hence a higher fat oxidation. Furthermore, part of
the weight loss may be related to the negative fluid balance as water intake usually
decreased during Ramadan.18,21
Lipid Profile
Many studies showed that the values of TC, TG, VLDL-C, LDL-C, cholesterol/HDL
and LDL/HDL ratio were significantly decreased and HDL-C increased significantly
after Ramadan fasting in healthy, nondiabetic subjects.23,24 Such beneficial effects
were independent of taking statins and were maintained for at least 1 month after
Ramadan.25,26 Similar to diabetic patients, the changes in lipid parameters of healthy
subjects may vary depending on the dietary habits and level of physical activity.
Increased consumption during Ramadan of monounsaturated and polyunsaturated
fatty acids as well as decreased consumption of saturated fatty acids were associated
with favorable changes in lipid profile.23
Blood Pressure
It is well known that fasting is associated with catecholamine inhibition and
reduced venous return, causing a decrease in the sympathetic tone, which leads to a
decrease in blood pressure. In line with these hypotheses, many studies showed that
Ramadan fasting led to significant decrease in systolic and diastolic blood pressure in
normotensive as well as hypertensive patients.18,27,28 Hypertensive patients may fast
Ramadan safely if they continue to take their previous antihypertensive medications.27
49
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49
restricted upon fasting.18 Fasting during Ramadan leads also to a significant decrease
in homocysteine concentrations, which may play a significant role in the development
of atherosclerosis.29
Heat shock proteins (HSP) are ubiquitously synthesized in virtually all species and
it is hypothesized that they might have beneficial health effects. Recent studies have
identified circulating Hsp as an important mediator in inflammation.30 A recent study
involving 32 healthy men showed that Ramadan fasting increased serum Hsp along
with an improvement in serum lipid profile.31
Oxidative stress can be defined as an imbalance between the production of
reactive oxygen species (ROS) and the antioxidative defense mechanisms of the
body. There is now considerable data to support a link between oxidative stress,
cardiovascular tissue injury, cancers and ageing.32 Ramadan fasting may alleviate
oxidative stress; especially if accompanied with body weight and fat mass percentage
reductions.33,34 The ability of Ramadan fasting to reduce oxidative stress and the levels
of proinflammatory cytokines upon fasting may drive a speculation that Ramadan
fasting could have positive effects in patients who suffer from rheumatoid arthritis, a
disease that had been reported to be characterized by an oxidative damage as well as
an increased activity of the proinflammatory cytokines.18,35
50
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51
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51
Digestive System
Fasting in Ramadan allows the digestive system to rest from the normal demands of
processing and breaking down food, freeing up system resources to cleanse and purify
the body of accumulated harmful dietary toxins, thereby allowing more effective
healing and tissue repair. The liver also takes rest as it is the main factory of food
metabolism. To achieve this benefit, Muslims should adhere to the tradition (sunnah)
by abstaining from having too much food after breakfast. The Prophet Muhammad
(peace be upon him) said, The son-of-Adam never fills a bowl worse than his belly.
Some bites are enough for man to prop his physique. Had he wished otherwise, then
one third for his food, and one third for his drink, and one third for his breath. It is of
benefit to the body that the break of fasting starts with some dates (as indicated in the
Prophetic tradition). Dates are rich in glucose and fructose, which have a great caloric
benefit especially for the brain, and are useful in raising the level of sugar gradually in
blood, thus reducing the feeling of hunger and the need for large quantities of food.
Regarding the impact of Ramadan fasting on patients with gastrointestinal
diseases, the findings have been heterogeneous. Mehrabian et al. showed that
patients under proton pump inhibitors treatment can fast safely and will not face an
increased risk of complications.40 It has even been claimed that long-term hunger
may contribute to healing of persistent ulcers by improving the control of stomach
secretion.41 Moreover, Tavakkoli et al. found no correlation between Ramadan fasting
and the severity of inflammatory bowel diseases.42
Renal Function
There is a growing public belief that Ramadan fasting deteriorates kidney function in
some patients. This seems to be not always true. A recent study showed that Ramadan
fasting did not have adverse effects on renal function parameters; rather it improved
these parameters.43 Furthermore, several studies conducted on kidney transplant
patients showed no significant changes in the serum values of creatinine, urinary
protein excretion or glomerular filtration rate during fasting.44 Renal protective effect
of fasting may be explained by its antioxidative properties.43 Fluid deprivation during
fasting may cause volume contraction and moderate dehydration. The prophetic
tradition mandates that Suhur (a meal before the dawn) be delayed and Iftar (the
breakfast meal) be expedited, thus reducing the time period of dehydration as much
as possible. The effect of Ramadan fasting on patients with renal impairment is still
unclear, although findings of some studies have shown good tolerance and safety of
fasting in these patients.45
52
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53
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Chapter 6: Beneficial Effects of Ramadan Fasting on Health
53
Flow chart 3: Suggested mechanisms for the positive effects of Ramadan fasting on brain function
and mental health
calories would be the equivalent of reducing about 100 calories a day in a human
diet.63 In another animal study, a group of researchers found that IF was able to delay
the progression of a variety of tumors and to potentiate chemotherapy, improving
cancer-free survival.64
In humans, there are no firm conclusions about the relation between IF and cancer
risk. However, we would expect anti-cancer role of IF and caloric restriction; as they
may modulate signaling molecules involved in carcinogenesis (Flow chart 4).
54
Section 1: Overview
Chapter 6: Beneficial Effects of Ramadan Fasting on Health
54
Flow chart 4: Suggested mechanisms for the anticancer effect of Ramadan fasting
Abbreviations: IGF-1Insulin-like growth factor 1; IGF1-RInsulin like growth factor 1 receptor; IRS
Insulin receptor substrate; PI3KPhosphatidylinositol 3-kinase; AMPK:AMPActivated protein kinase
55
Section 1: Overview
Chapter 6: Beneficial Effects of Ramadan Fasting on Health
55
of impulses and helps develop good behavior. This purification of body and soul
harmonizes the inner and outer spheres of an individual.20
Muslims encouraged being doing more acts of piety, prayers, charity or reading
the Quran. Recitation of the Quran not only produces a tranquility of heart and mind,
but improves the memory. According to a study by Dr Ahmed El Kadi, of Akber Clinic
in Panama, Florida, the recitation of or listening to the Quran have positive effects on
the body, the heart and the mind, irrespective of whether the listener was a Muslim or
non-Muslim, Arab or non-Arab.67
Muslims cannot consume alcohol and use smoke in any form during the month of
Ramadan. Those people who are addicted to such habits, it is the best time for them to
quit these habits, which are spoiling their health and wasting their money. Since they
are restraining themselves from these habits for one month, they should continue to
do so, for the rest of their life. In the United Kingdom, the Ramadan model has been
used by various health departments and organizations to reduce cigarette smoking
among the masses, especially among Africans and Asians.68
CONCLUSION
Ramadan fasting has numerous benefits on diabetic and healthy subjects. It
induces favorable changes on metabolic parameters, reduces oxidative stress and
inflammation, promotes cardiovascular benefits, improves brain function and boots
immunity. Ramadan fasting has also spiritual, social and psychological benefits.
Ramadan fasting would be an ideal recommendation for treatment of some metabolic
and inflammatory diseases. It should be noted however that Ramadan benefits require
some careful considerations benefits such as necessity of an adequate pre-Ramadan
medical assessment and education as well as conservation of a healthy dietary habits
and adopting a healthy lifestyle.
Conflict of interest: None to declare.
ACkNOwLEDGMENTS
We are thankful to Dr Basma Ben Naceur, Nadia Charfi, Fatma Mnif, Mohamed
Dammak, Nabila Rekik, Mohamed Habib Sfar, Mohamed Abid for their contribution
in the preparation of this manuscript.
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26. Adlouni A, Ghalim N, Sale R, et al. Beneficial effect on serum apo AI, apo B and Lp AI
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27. Perk G, Ghanem J, Aamar S, et al. The effect of the fast of Ramadan on ambulatory blood
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Relat Disord. 2011;9:157-61.
29. Aksungar FB, Topkaya AE, Akyildiz M. Interleukin-6, Creactive protein and biochemical
parameters during prolonged intermittent fasting. Ann Nutr Metab. 2007;51:88-95.
30. Njemini R, Bautmans I, Onyema OO, et al. Circulating heat shock protein 70 in health,
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31. Zare A, Hajhashemi M, Hassan ZM, et al. Effect of Ramadan fasting on serum heat shock
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33. Ibrahim WH, Habib HM, Jarrar AH, et al. Effect of Ramadan fasting on markers of oxidative
stress and serum biochemical markers of cellular damage in healthy subjects. Ann Nutr
Metab. 2008;53:175-81.
34. Faris MA, Hussein RN, Al-Kurd RA, et al. Impact of Ramadan intermittent fasting on
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doi: 10.1155/2012/802924.
35. Schuerwegh AJ, Dombrecht EJ, Stevens WJ, et al. Influence of pro-inflammatory (IL-1 alpha,
IL-6, TNF-alpha, IFN-gamma) and antiinflammatory (IL-4) cytokines on chondrocyte
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36. Halberg N, Henriksen M, Sderhamn N, et al. Effect of intermittent fasting and refeeding
on insulin action in healthy men. J Appl Physiol. 2005;99:2128-36.
37. Salim I, Al Suwaidi J, Ghadban W, et al. Impact of religious Ramadan fasting on
cardiovascular disease: a systematic review of the literature. Curr Med Res Opin.
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38. Khafaji HA, Bener A, Osman M, et al. The impact of diurnal fasting during Ramadan on
the lipid profile, hs-CRP, and serum leptin in stable cardiac patients. Vasc Health Risk
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39. Katare RG, Kakinuma Y, Arikawa M, et al. Chronic intermittent fasting improves the
survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling
pathway. J Mol Cell Cardiol. 2009;46:405-12.
40. Mehrabian A, Homayouni R, Hashemi M, et al. Is healing of duodenal ulcer delayed by
Ramadan fasting? Koomesh. 2007;8:67-72.
41. Johnston DA, Wormsley KG. The effects of fasting on 24-h gastric secretion of patients with
duodenal ulcers resistant to ranitidine. Aliment Pharmacol Ther. 1989;3:471-9.
42. Tavakkoli H, Haghdani S, Emami MH, et al. Ramadan fasting and inflammatory bowel
disease. Indian J Gastroenterol. 2008;27:239-41.
43. El-Gendy OA, Rokaya M, El-Batae HE, et al. Ramadan fasting improves kidney functions
and ameliorates oxidative stress in diabetic patients. World Journal of Medical Sciences.
2012;7:38-48.
44. Khedmat H, Taheri S. Ramadan fasting and transplantation: current knowledge and what
we still need to know. Saudi J Kidney Dis Transpl. 2010;21:417-20.
45. Bernieh B, Al Hakim MR, et al. Fasting Ramadan in chronic kidney disease patients:
clinical and biochemical effects. Saudi J Kidney Dis Transpl. 2010;21:898-902.
46. Aksungar FB, Eren A, Ure S, et al. Effects of intermittent fasting on serum lipid levels,
coagulation status and plasma homocysteine levels. Ann Nutr Metab. 2005;49:77-82.
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47. Sarraf-Zadegan N, Atashi M, Naderi GA, et al. The effect of fasting in Ramadan on the
values and interrelations between biochemical, coagulation and hematological factors.
Ann Saudi Med. 2000;20:377-81.
48. Ibrahim O, Kamaruddin N, Wahab N, et al. Ramadan fasting and cardiac biomarkers
in patients with multiple cardiovascular disease risk factors. The Internet Journal of
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49. Aybak M, Trkolu A, Sermet A, et al. Effect of Ramadan fasting on platelet aggregation in
healthy male subjects. Eur J Appl Physiol Occup Physiol. 1996;73:552-6.
50. Latifynia A, Vojgani M, Gharagozlou MJ, et al. Neutrophil function (innate immunity)
during Ramadan. J Ayub Med Coll Abbottabad. 2009;21:111-5.
51. Chaouachi A, Coutts AJ, Wong del P, et al. Haematological, inflammatory, and
immunological responses in elite judo athletes maintaining high training loads during
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52. Walrand S, Moreau K, Caldefie F, et al. Specific and nonspecific immune responses to
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53. Meazza C, Pagani S, Travaglino P, et al. Effect of growth hormone (GH) on the immune
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54. Abbas SM, Basalamah AH. Effects of Ramadhan fast on male fertility. Arch Androl.
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55. Martin B, Mattson MP, Maudsley S. Caloric restriction and intermittent fasting: two
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66. Daradkeh TK. Parasucide during Ramadan in Jordan. Acta Psychiatr Scand. 1992;86:
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68. Farren C, Naidoo J. Smoking cessation programmes targeted at black and minority ethnic
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Section
Nonpharmacological
Management
CHAPTERS
7. Monitoring Diabetes Patient during Ramadan
8. Nutrition Recommendations for Persons with
Diabetes during Ramadan
9. Physical Activity in Ramadan
10. Stress Management and Diabetes in Ramadan
Chapter
Abstract
The development of tools to monitor diabetes treatments has been one of the important landmarks in
the management of diabetes mellitus and has revolutionized diabetes care with significantly influence
on disease-outcome. Glycosylated hemoglobin (HbA1c) and Self Monitoring of Blood Glucose (SMBG)
are the 2 most widely studied and cited monitoring tools. HbA1c reflects overall control and risk of
complications whereas SMBG charts the pattern of daily glucose profile. On the other hand SMBG is
the main tool for day-to-day care and decision making and should be an essential component and
education before Ramadan; physician could avail this important spiritual occasion to make their
patients learn how to monitor their glucose and use the information to better manage their diabetes
not just during Ramadan but well beyond to achieve the target goals.
INTRODUCTION
62
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Chapter 7: Monitoring
Management
Diabetes Patient during Ramadan
62
Ramadan and without proper glucose monitoring; even the best of patients or
physicians cannot decide the changes in management plan necessary. Hence it is
important that in pre-Ramadan patient education session, they are educated so
they acquire the knowledge and skills to stratify their risk for fasting and to adjust
their therapy so as to keep the blood glucose in the desired range without hypo- or
hyperglycemia.
The landmark epidemiological diabetes in Ramadan study, EPIDIAR 2001,1 has
shown that fasting during Ramadan exposes these patients to an increased risk of
hypoglycemia, hyperglycemia and may even lead to diabetes ketoacidosis (DKA) and
nonketotic hyperosmolar hyperglycemia (NKHH). As far as SMBG in Type 2 diabetes
mellitus (T2DM) is concerned, the findings are not consistent regarding its usefulness
in patients who are not on insulin in outside of Ramadan2 but like pregnancy in
diabetes, Ramadan provides a good opportunity to educate and motivate patients
about the utility of this tool and they are willing to learn for their aspirations to fast
during this holy month. In a recent systemic review by Clar et al. they concluded
against the clinical effectiveness of SMBG in improving glycemic control in people
with T2DM on oral agents and stated it to be not cost-effective. On the other hand, the
fasting during Ramadan stresses the recommendations from International Diabetes
Federation (IDF) guidelines on SMBG3 in noninsulin treated T2DM. The guidelines
summarizes that SMBG should be used only when patient with diabetes have the
knowledge skills and willingness to incorporate SMBG monitoring and therapy
adjustment into their diabetes care plan in order to attain agreed treatment goals.
Nevertheless, in some studies, SMBG has demonstrated the efficacy in improving
outcomes. Even before the modern convenient and easy to use glucometers became
available, Evan et al.4 published his findings that SMBG is useful and specifically that
increasing the frequency of SMBG was linearly correlated with reductions in HbA1c
among Type 1 diabetes mellitus (T1DM) patients. Among patients with T2DM, a
higher frequency of SMBG was associated with better glycemic control in those who
were on insulin and were able to adjust their regimen.5
Ramadan Education and Awareness in Diabetes (READ) program6 provided
structured education to one group comprising education about physical activity, meal
planning, glucose monitoring, hypoglycemia, dosage and timing of medications and
showed significant decrease in the total number of hypoglycemic events.
The frequency of glucose monitoring is not well defined or evidence based
although most experts agree that T1DM patients should monitor their glucose at
least four times a day, most commonly fasting, before each meal and bedtime. The
new insights into the importance of postprandial hyperglycemia also emphasizes
the need for post-meal glucose monitoring is equally if not more important. For
patients with T2DM, frequency of monitoring varies, depending on the medication
and whether the patients are adjusting their dose or have achieved their targets. As
patients with T2DM usually do not adhere to frequent blood glucose monitoring, it
has been recommended that people with diabetes who use insulin should perform
SMBG at least four times per week, of which at least two should be fasting and two
post-meal.4
As per IDF guidelines, there are situations in which short term focused SMBG
may be beneficial even to noninsulin treated T2DM patients. Although Ramadan
63
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Management
Diabetes Patient during Ramadan
63
and fasting are not mentioned specifically in the guidelines, because of the risk of
hypoglycemia, this recommendation should be implemented in this setting till we
have more evidence available. Similarly meal-based SMBG is also very important in
helping patients understand the impact of postprandial hyperglycemia particularly
seen after rich iftar dinner during Ramadan.7
In the EPIDIAR study,1 it was reported that only 67 percent of T1DM patients and
37 percent T2DM patients were monitoring their blood glucose. The most commonly
referenced recommendation for management of diabetes during Ramadan8
makes it essential that patients intending to fast during Ramadan should have the
means to monitor their blood glucose levels multiple times daily. Although the
recommendations are based on expert opinion mostly, most diabetologists managing
these patients recognize that SMBG is significantly helpful in decision making
about dose adjustments for both the physicians and self adjusting patients. It is also
recommended that importance of SMBG should be an essentials component of
structured education program before Ramadan in all centers and clinics managing
these patients.
There is little published data about the timings and frequency of SMBG in the
context of Ramadan. In general, it is agreed that pre-Iftar (before the sunset meal)
blood glucose represents fasting blood sugar outside Ramadan. It is important that
patients in particular are educated that in religion, pricking and drawing blood
for SMBG during the fast does not break or violate the fast otherwise due to this
misunderstanding, they do not check blood glucose till after breaking their fast (iftar).
Guideline published by Azizi et al.9 suggest that SMBG should be performed just
before the sunset meal and 23 hours after that iftar meal. It could also be performed
before the Suhur meal to adjust the insulin dose in some patients. The recent Ramadan
Prospective Diabetes Study10 used a 10 point monitoring schedule in their study, with
2 points on each day for 5 consecutive days.
We know that in studies and clinical trials due to close observation and
supervision, patients are more likely to adhere and those who do not are excluded
from analysis, but in real life situation to expect such compliance is usually not
rewarded. In our center, we advise patients to agree to monitor for first three days to
get a feel of glucose profile and adjust their dose. They are educated the check their
blood glucose on getting up in the morning and around noon time to first to assess
the risk of hypoglycemia. If on these points their blood glucose is more than 100 mg/
dL, in general the risk of hypoglycemia is low but still varies with their medication.
Then again they should check pre-Iftar and should be above 80 as expected for fasting
blood sugar outside of Ramadan after 812 hours overnight fast. If the first 2 points
are less than 100 mg/dL, they should be watchful and if less than 80 mg/dL, they
should break the fast and adjust their Suhur dose for next day. Once this has been
taken care of, they should check their post-Iftar (main sunset meal) to assess the risk
of hyperglycemia and adjust the Iftar dose of medications. Pre-suhur SMBG is also
useful to assess risk of nocturnal hypoglycemia and adjust dose at suhur. Patients
should be given a Ramadan logbook to keep a record of SMBG, with Ramadan point
reference exemplified in Figure 1.
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Chapter 7: Monitoring
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64
GLYCOSYLATED HEMOGLOBIN
The use of glycosylated hemoglobin (HbA1c) has become a standard for assessing
long-term glycemic control and most studies have correlated HbA1c level with the risk
of developing complications. But due to average red blood cell life of being 120 days,
and as the glycosylation occurs continuously, the HbA1c measurement represents
predominantly the level of control during the previous 2 months period. In the
setting of Ramadan, it may be a useful monitoring tool for retrospective assessment
of worsening or improvement in diabetes control but is rarely useful in helping the
management during Ramadan.
Clinical trials studying new therapies may still use it to document improvement
or non-worsening of glycemic control during Ramadan which is very common due to
over-eating and less strict glycemic control to avoid hypoglycemia during the fast.
FRUCTOSAMINE
The main advantage of fructosamine is that it is a measure of blood glucose control
over the past 23 weeks and hence could give more precise information about
glycemic control in the preceding Ramadan. Although a better tool compared to
HbA1c in relation to Ramadan and a useful tool for clinical trials to assess intervention
around Ramadan, its value in everyday care is not established.
65
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Diabetes Patient during Ramadan
65
REFERENCES
1. Salti I, Bnard E, Detournay B, et al. EPIDIAR study group. Population based study of
diabetes and its characteristics during the fasting month of Ramadan in 13 countries.
Diabetes Care. 2004;27:2306-11.
2. Clar C, Barnard K, Cummins E, Aberdeen Health Technology Assessment Group. Selfmonitoring of blood glucose in type 2 diabetes: systematic review. Health Technol Assess.
2010;14(12):1-140
3. International Diabetes Federation, 2009: Self-Monitoring of Blood Glucose in Non-InsulinTreated Type 2 Diabetes; Recommendations based on a Workshop of the International
Diabetes Federation Clinical Guidelines Taskforce in collaboration with the SMBG
International Working Group. [online] Available from www.idf.org and at www.smbg-iwg.
com. [Accessed June, 2013]
4. Evan M Benjamin. Self-monitoring of blood glucose. The Basics Clinical Diabetes 2002;
20(1):45-7
5. Franciosi M, Pellegrini F, De Berardis G, et al. Self-monitoring of blood glucose in
non-insulin-treated diabetic patients: a longitudinal evaluation of its impact on metabolic
control. Diabet Med. 2005;22:900-6.
6. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ)
programme for Muslims with Type 2 diabetes who fast during Ramadan. Diabet Med.
2010;27(3):327-31.
7. 2007 IDF Guideline for Management of Post meal Glucose: 2007. [Online] Available from
www.idf.org. [Accessed June, 2013].
8. Gerich JE, Odawara M, Terauchi Y. The rationale for paired pre- and postprandial selfmonitoring of blood glucose: the role of glycemic variability in micro- and macrovascular
risk. Curr Med Res Opin. 2007;23(8):1791-8.
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66
Chapter
Nutrition Recommendations
for Persons with Diabetes
during Ramadan
Sarita Bajaj
Abstract
Ramadan the sacred month of Islam, dutifully observed by all the adult Muslims. Sawn is one of
the five pillars of Islam, where the individual is required to keep fast from dawn to dusk every day
of the month, when they are not allowed to drink or eat anything, even oral medications are not
permissible. Individuals are allowed to have a morning meal before sunrise, i.e. Suhur and a meal
after evening, i.e. Iftar.
This period of fasting, however, can cause serious complications in people with chronic illnesses
like diabetes. In fact the holy Quran exempts such people from keeping fast. But because of the
strong faith and conviction, despite all contraindication, people sometimes refuse to do so. With the
rising prevalence of diabetes because of the changing lifestyle, management of diabetes during this
period of fasting has become a subject demanding singular consideration. The fundamental aspects
of management include medical counseling, nutrition and readjustment of treatment regimen. This
articles attempts to give a comprehensive protocol for the management of diabetics observing fast
during the period of Ramadan.
INTRODUCTION
Chapter
8:
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Management
Persons with Diabetes during Ramadan
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68
Although it is obligatory on part of all adult Muslims to observe fast during the
month of Ramadan, but there are certain exemptions which are as follows:
People suffering from chronic illnesses
Pregnancy
Menstruation
Travel.
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Persons with Diabetes during Ramadan
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Body Weight
During fasting it has been noted that there is a decreased physical activity and a
tendency to overeat when the fast is broken. During Ramadan more dishes and
refined foods are prepared than other days. This may lead to increased food intake. It
Chapter
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Recommendations for
Management
Persons with Diabetes during Ramadan
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70
is also thought that patients with the fear of hypoglycemia avoid exercising leading to
minimal or no decrease in body weight or even increase in body weight despite the
fast. This controversy in body weights has been noted when a review of the literature
on weight changes in diabetics was done. In normal persons different trends in
changes in body weight are also noted during Ramadan. A study by Frost and Pirani,
where energy intake was significantly higher during Ramadan than after Ramadan
(3,680 kcal/day vs. 2,425 kcal/day) revealed a mean weight increase from 58.9 kg to
60.3 kg at the end of Ramadan.7 In both normal and diabetic population, especially
in overweight diabetics, it seems that regulation of food intake and physical activity is
important to attain desirable weights during and after Ramadan.
Lipid Metabolism
In Islam there is no restriction on the quantity or type of food after opening fast and
this may contribute to the differences noticed in lipid profiles. In both normal persons
and diabetics there have been conflicting results on the effect of dietary fat on changes
in blood cholesterol levels.
Patients with Type 2 or Type 1 diabetes mostly show no change or slight decreases
in cholesterol and triglycerides.
Like in healthy persons, several studies have reported increases in high-density
lipoprotein (HDL) cholesterol in diabetics during Ramadan.8,9 One report points
to an increase in low-density lipoprotein (LDL) cholesterol and a decrease in
HDL-cholesterol. The differences in the results could be explained by the lack of
standardizing energy intake and physical activity, which could have an effect on the
lipid metabolism
A review by Nomani10 has suggested that when energy is limited, a dietary fat
increase from 30 percent36 percent favors a reduced breakdown of body protein
including labile LDL cholesterol receptors that are protein in nature.
There is an increase in blood cholesterol levels with increasing or decreasing
weight from normal weight levels. During Ramadan, no significant difference was
noticed in blood cholesterol levels before and after fasting period when there was no
significant difference in body weight either.
Uric Acid11
Several studies have reported non-significant increases in urea and uric acid
concentrations during Ramadan. Increase in uric acid correlated positively with
weight loss. Uric acid is formed as a product from purine metabolism and during
Ramadan with weight loss it is postulated that this factor and the concomitant
dehydration while fasting may lead to raised uric acid levels.
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Persons with Diabetes during Ramadan
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71
Adjustment of the drug regimen (shifting from a long-acting drug to short acting
drug regimen to prevent hypoglycemic episodes)
Encouraging physical exercise
Educating about the danger signs and risk factors associated with hypoglycemia,
dehydration and thrombosis.
Hypoglycemia
Reduced food intake is a well-known indicator for developing hypoglycemia and
therefore is quite common during Ramadan. Approximately 4 percent of deaths may
occur because of hypoglycemia during this period. EPIDIAR study indicated 4.7 fold
increase in incidence of hypoglycemia in Type 1 diabetes and 7.5-fold increase in
Type 2 diabetes during Ramadan.
Hypoglycemia is defined as blood sugar levels below 70 mg percent. If not managed
promptly it can be fatal. It can be easily identified if a high-risk behavior is present
such as being discussed, i.e. fasting in diabetics and can also be easily managed
bedside till further assistance arrives by the lay man themselves. Identification of the
risk factor and relating it to symptomatology can be life-saving. Thereby it is important
to appraise the diabetic patients and their family members about the symptoms when
they should suspect hypoglycemia.
Symptoms associated with hypoglycemia:
Feeling hungry
Tingling of the lips
Trembling or shakiness
Blurred vision
Profuse sweating
Difficulty in concentration
Anxiety or irritability
Vagueness or confusions
Altered sensorium
Palpitation
Seizure
Loss of consciousness
Coma.
Hyperglycemias
EPIDIAR study indicated a five-fold increase in the incidence of hyperglycemia
requiring hospitalization during Ramadan fasting.1 This can be attributed to excessive
Chapter
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Section
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2: Nonpharmacological
Recommendations for
Management
Persons with Diabetes during Ramadan
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72
lowering of the glucose lowering medications as well as excessive food intake postfasting period.
Hyperglycemia is defined as blood glucose level more than 300 mg percent.
Symptoms pertaining to hyperglycemia:
Weight loss
Headache
Fatigue
Loss of concentration
Increased thirst
Frequent urination.
Diabetic Ketoacidosis
Patients with high blood glucose levels before fasting are at increased risk for
developing diabetic ketoacidosis. It is a medical emergency which can prove fatal and
has to be aggressively treated.
Symptoms associated with diabetic ketoacidosis:
Nausea and vomiting
Excessive thirst
Frequent micturition
Abdominal pain which can be mild to severe in intensity
Shallow and fast respiration, i.e. kussmauls breathing
Lethargy
Altered sensorium
Loss of consciousness and coma.
Chapter
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2: Nonpharmacological
Recommendations for
Management
Persons with Diabetes during Ramadan
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73
Moderate Risk
Well-controlled patients treated with short acting insulin secretagogue, sulfonylurea,
insulin, or taking combination oral or oral plus insulin treatment.
Low-risk
Well-controlled patients treated with diet alone, monotherapy with metformin,
dipeptidyl peptidase-4 inhibitors, or thiazolidinediones who are otherwise healthy.
Medical Counseling
Diabetics who intend to keep fast during the month of Ramadan shall visit their family
physician or local practitioner at least a month before for the complete assessment of
Chapter
8:
Section
Nutrition
2: Nonpharmacological
Recommendations for
Management
Persons with Diabetes during Ramadan
74
74
the general condition of the patient as well as to assess the degree of diabetic control
by the patient in the past few months. The physician should also determine if any
comorbities are present or not.
This would help the physician to stratify the patient according to the risk factors
present.
Physician should duly forewarn the concerned individual about the complications
associated and restrain them from observing the fast.
Dietary Advice
Chapter
8:
Section
Nutrition
2: Nonpharmacological
Recommendations for
Management
Persons with Diabetes during Ramadan
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75
Home-based Management
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8:
Section
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2: Nonpharmacological
Recommendations for
Management
Persons with Diabetes during Ramadan
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Chapter
8:
Section
Nutrition
2: Nonpharmacological
Recommendations for
Management
Persons with Diabetes during Ramadan
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Chapter
8:
Section
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2: Nonpharmacological
Recommendations for
Management
Persons with Diabetes during Ramadan
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78
REFERENCES
1. Salti I, Benard E, Detournay B, et al. The EPIDIAR Study Group. A population-based study
of diabetes and its characteristics during the fasting month of Ramadan in 13 countries:
results of the Epidemiology of Diabetes and Ramadan 1422/2001 (EPIDIAR) study.
Diabetes Care. 2004; 27: 2306-11.
2. Azizi F. Medical aspects of Islamic fasting. Med J Iran. 1996; 10:241-6.
3. Khatib F. Effect of fasting in Ramadan on blood glucose and plasma lipids in diabetics with
NIDDM.second international congress on health and Ramadan. 1997.p.42.
4. Ewis A, Afifi NM. Ramadan fasting and non-insulin dependent diabetes mellitus: effect of
regular exercise. Second international congress on health and Ramadan. 1997.p.42.
5. Al Nakhi A, Al Arouj M, Kandari A , Morad M. Multiple insulin injections during fasting
Ramadan in IDDM patients. Second international congress on health and Ramadan.
1997.p.77.
6. Azizi F, Siahkolah B. Ramadan fasting and diabetes mellitus. Int J Ramadan fasting Res.
1998; 28:17.
7. Frost G, Pirani S. Meal frequency and nutrition intake during Ramadan: a pilot study. Hum
Nutr Appl Nutr.1987;41A:47-50.
8. Uysal A, Erdagon M, Sahin G, Kamel N, Erdogan G. The clinical, metabolic and hormonal
effects of fasting on 41 NIDDM patients during the Ramadan 1997. Second international
congress on health and Ramadan. 1997.pp.45-6.
9. Dehagan M, Nafarabadi M, Navai L, Azizi F. Effects of fasting on lipid and glucose
concentration in type 2 diabetic patients. J Fac Med Shaheed Beheshti Univ Med Sci
Tehran. 1994;18:42-47.
10. Nomani MZA. Dietary fat, cholesterol and uric acid levels during Ramadan fasting.
International journal Ramadan fasting. 1997;1:1-6.
11. Fakhrzadeh H, Larijani B, Sanjari M, Baradar-Jalili R, Amini MR. Effect of Ramadan fasting
on clinical and biochemical parameters in health adults. Ann Saudi Med. 2003;23:223-6.
12. Deepa D Almeida. Faith and health connection: Nutrition during Ramadan. E bulletin.
CEDAR- Jebar Ali International Hospital. 2012;26:1-4.
13. Longo, Fauci, Kasper, Hauser, Jameson, loscalzo. Harrisons principles of internal
medicine. 18th edition.
14. Al-Arouj M, Bouguerra R, Buse J, Hafez S, Hassanein M, Ibrahim MA, et al.
Recommendations for Management of Diabetes during Ramadan. Diabetes Care 2005;
28:2305-11.
15. Benaji B, Mounib N, Roky R, Aadil N, Houti IE, Moussamih S, et al. Diabetes and Ramadan:
review of the literature. Diabetes Res Clin Pract. 2006;73:117-25.
16. Akram J, De Verga V. Insulin Lispro in treatment of diabetes during fasting month of
Ramadan. Diabet Med 1999;16:861-866.
17. Kadir A et al. Treatment of type 1 diabetes with insulin Lispro during Ramadan. Diabete
Metab. 2001;27:482-486.
18. Shaik S, James D, Morrissey J, Patey V. Diabetes care and Ramadan: fast or not to fast. Br J
Diabetes Vasc Dis 2001; 1:65-7.
19. Aslam M, Assad A. Drug regimens and fasting during ramadan: a survey in Kuwait. Public
health. 1986;100:49-53.
Chapter
Abstract
Despite being of a proven benefit in diabetes, exercise is one of the less implemented tools in clinical
practice. The goal is to provide a simple regime to accommodate the needs of fasting in Ramadan and
to avoid hypoglycemia, hyperglycemia, and hypovolemia. Meals should be also planned accordingly.
Risk of thrombosis in high-risk group patients like laborers, elderly and with other risk factors should
be addressed specifically, to prevent dehydration and hyper viscosity. However, professional sports
have been played and with their training in the late evening hours. Timing of exercise in others can
be as per their change of schedule in Ramadan. Aerobic and resistance both types of exercise can
be prescribed in Ramadan.
INTRODUCTION
80
80
81
81
82
82
DISCLAIMER
The authors received no funding and report no conflict of interest.
83
83
During Ramadan
T1DM
Glucose monitoring
REFERENCES
1. Trabelsi K, El Abed K, Trepanowski JF, et al. Effects of Ramadan fasting on biochemical and
anthropometric parameters in physically active men. Asian journal of sports medicine.
[online]. Available from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=328
9216&tool=pmcentrez&rendertype=abstract. [Accessed September, 2011].
2. Abir Zakaria, Inas Sabry AE. Ramadan-like fasting reduces carbonyl stress and improves
glycemic control in insulin treated type 2 diabetes mellitus patients. Life Science J.
2013;10(2):384-90.
3. Javad Fallah S. Ramadan fasting and exercise performance. Asian journal of sports
medicine. [online]. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi
?artid=3289179&tool=pmcentrez&rendertype=abstract. [Accessed September, 2010].
4. Mirzaei B, Rahmani-Nia F, Moghadam MG, et al. The effect of ramadan fasting on biochemical and performance parameters in collegiate wrestlers. Iranian journal of basic medical
sciences. [online] Available from http://www.pubmedcentral.nih.gov/articlerender.fcgi?a
rtid=3646235&tool=pmcentrez&rendertype=abstract. [Accessed November, 2012].
5. Stannard SR. Ramadan and Its Effect on Fuel Selection during Exercise and Following
Exercise Training. Asian journal of sports medicine. [online]. Available from: http://www.
pubmedcentral.nih.gov/articlerender.fcgi?artid=3289214&tool=pmcentrez&rendertype=
abstract. [Accessed September, 2011].
6. Salti I, Benard E, Detournay B, et al. A population-based study of diabetes and its
characteristics during the fasting month of Ramadan in 13 countries. Diabetes Care.
2004;27(10):2306-11.
84
84
Chapter
10
Abstract
Low quality of life and poor glycemic status arises from stress in diabetes. Stress may be present
in patients in both, those who are diabetic and fast; and those who are diabetic and do not fast in
Ramadan. From dietary indiscretion to altered sleep due to modern Ramadan practices; and the
changing treatment regimen also add to stressfulness in patients. This chapter describes stress management in four prongs; patient, physician, peer and folk level. Directly diabetes-related distress can
influence healthy status of patients, while indirectly it demotivates them to pursue further control. To
overcome the distress of stress counseling has to be provided at all levels to all patients in need. The
treating physician should impart technical details of coping up as illustrated and be tactical so that it
is implemented by the patient in manner that it not only helps in Ramadan, but also in post-Ramadan.
INTRODUCTION
86
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Chapter 10: StressManagement
Management and Diabetes in Ramadan
86
MECHANISM
Cortisol and Sleep
Stress leads to increased catecholamines and hypercortisolism, with consequent
hyperglycemia. Hypercortisolemia is one factor in the setting of chronic stress,
confirmed by salivary cortisol, as observed in Ramadan fasting. Also, lack of sleep
contributes to stress in addition due to altered hypothalamo-pituitary-adrenal axis.
Owing to benefits of modern lifestyle, long waking hours and sedentary profile, these
two factors add further to dysmetabolic status of individuals and increase in insulin
resistance.1
Altered Sleep
In some patients night may be spent in praying or socializing in some or just waiting
till sunrise meal (Suhur) in some. This affects the quantity as well as quality of sleep.
This is also important in countries, e.g. polar regions with long fasting hours and less
sleep hours in summer season and vice versa.
Treatment Regimen
The changed and the changing regimen, in management of diabetes in Ramadan
can affect a patients control over various aspects of diabetes. With stress and its
consequent hyperglycemia, further demands of increase in dosages of insulin may be
needed for glycemic control in some patients.
Anxiety and/or ability for fasting and awareness of the disease problem in some
patients also effects in Ramadan.
However, by understanding the difficulties of an individual patient and with
proper counseling and stress management these can be alleviated.
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Management and Diabetes in Ramadan
87
THE SOLUTION
At Patients Level
Self-management forms the main basis of diabetes stress management, irrespective
of the patients literacy levels. This also depends on the treating physician or his team
by the time given to individual patients in daily practice. At the patients levels the
following four aspects should be taken care:
Meals
Following the diet as per individual requirement brings patients closer to targets and
reduces stress. Although, The Prophet Muhammad (peace be upon him) use to break
the fast with dates and water, the modern style has changed considerably into feasting
at sunset meal (Iftar) and leading to the constellation of chronic stressful disorders
due to dysmetabolism.1 Patients should be advised to avoid carbohydrate rich and
foods high in saturated fats.
Medications
Patients taking their tablets/insulin by themselves on time. Adding anxiolytics during
Ramadan may not be acceptable to patients if it increases their sleep or hampers
daily activity, as patients would like to be alert during Ramadan. Patients on multiple
medications including insulin (see chapter on Insulin and Type 2 Diabetes Mellitus)
may find it stressful if not implemented in a patient centered way.
Monitoring
Self-monitoring of blood glucose is the best immediate incentive the patients gets and
helps them adjust the meals and treatment dosages as advised by the physician. While
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Management and Diabetes in Ramadan
88
in Ramadan frequency of testing can be decreased after first few days once control is
evident by the changed meals and medication (tablet or insulin).2 Improved glycemic
control positively affects quality of life by reducing lethargy and cognitive distress.3
At Physician Level
Recheck
Diet tracking allows us to know dietary indiscretions and reinforce on patients.
This along with exercise rechecks, further helps in reducing various components of
metabolic syndrome.
Reassess
Diabetes status overtime should be reassessed to know any impending emergency
or complication, so that prompt action may be taken even before Ramadan. Thus,
managing these will decrease the mental burden to patients.
Restress
Motivation should be a part of every visit subject to patients willingness to maintain
various parameters as normal as possible. Repeat when required in subsequent fasting
years in Ramadan, as in the long-term, effectiveness of counseling reduces overtime.
Receive
Physicians should receive training to enquire role of religion and spirituality to
enhance patients coping and better self-management of diabetes.4
At Peer Level
Group Discussions
They create awareness about realities that there are others with similar issues and
stops the why me attitude of some patients. This can be done by physician or cultural
and religious leaders.4
Group Visits
Patients of the same family5 or area can be called for a group visit as a part of stress
management session. This reduces the stress and strain of traveling alone and gives a
better platform for understanding towards their problem in Ramadan.
At Folk Level
Family therapy5 forms the most important prong in the stress management of
diabetes, also in Ramadan. Family education is important and regular sessions with
them change the outlook of diabetes patients and their family. It can be done in the
following way:
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Chapter 10: StressManagement
Management and Diabetes in Ramadan
89
Perishing Stress
Parents of young adults need to be counseled along with patients to cope up in a
positive way. Financial stress and stressful moments in life of patients and family
needs to be dealt tenderly, for at times the young may be supporting an elderly/old
diabetic or vice versa. Healthy coping is stressed upon, for better outcomes in diabetes
management. Patients and families at polar regions with long fasting hours may
benefit with healthy coping in reducing stress.
Putting it Down
All sorts of conflict within the family has to be solved assertively to improve patients
metabolic profile and familys adjustment towards patients. This helps the maximum,
in the management of diabetes and involves improvement in all viz. physical, mental
and social aspects of life. Always ascertain that patients family knows about the diet,
exercise and treatment regimen prescribed during Ramadan.
CLINICAL IMPLICATIONS
Stress management in Ramadan gives a chance to clear out the negative perceptions
about the diabetes.
Stressing upon the belief and attitude of patients can bring about reduction in
stress levels and better diabetes management.
This also improves quality of life during Ramadan and fewer complications.
With proper stress management, even intensive treatment regimens can be
implemented easily, subject to time spent with the patient.
Ongoing stress management is a must in a diabetic patients life, not only for
Ramadan, but also otherwise to achieve long-term goals for diabetes.
When stress management is taken care, patients do well and all religious obligations
can be carried out in a happy and healthy mode, and consequently diabetes outcomes.
The treating physician/endocrinologist should impart technical details of coping up
and be tactical so that it is implemented by the patient in manner that it not only helps
in Ramadan, but also post-Ramadan.
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90
Stress free
Sleep stress
Safety
Modernization stress
Dietary stress
At patients level
At physician level
At peer level
At family level
meditation
and
This multipronged approach will help the doctor to reduce stress levels pre, during
and post-Ramadan.
RECOMMENDATIONS
See Table 1.
DISCLAIMER
The authors received no funding and report no conflict of interest.
REFERENCES
1. Bahijri S, Borai A, Ajabnoor G, et al. Relative metabolic stability, but disrupted circadian
cortisol secretion during the fasting month of Ramadan. PloS one. 2013;8(4):e60917.
[online]. Available from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=363
0175&tool=pmcentrez&rendertype=abstract. [Accessed June, 2013]
2. Ahmad J, Pathan MF, Jaleel MA, et al. Diabetic emergencies including hypoglycemia
during Ramadan. Indian J Endocrinol Metab. 2013;16(4):512-5. [online]. Available from
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3401746&tool=pmcentrez&
rendertype=abstract. [Accessed June, 2013].
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3. Hajos TRS, Pouwer F, De Grooth R, et al. The longitudinal association between glycaemic
control and health-related quality of life following insulin therapy optimisation in type
2 diabetes patients. A prospective observational study in secondary care. Quality of
life research : an international journal of quality of life aspects of treatment, care and
rehabilitation. 2013;21(8):1359-65. [online]. Available from http://www.pubmedcentral.
nih.gov/articlerender.fcgi?artid=3438404&tool=pmcentrez&rendertype=abstract.
[Accessed June, 2013].
4. Kalra S, Balhara YP, Bantwal G, et al. National recommendations: Psychosocial
management of diabetes in India. Indian J Endocrinol Metab. 2013;17(3):376. [online].
Available from http://www.ijem.in/text.asp?2013/17/3/376/111608. [Accessed June,
2013].
5. Shaikh A. Family therapy in diabetes mellitus. IJEM. 2013;238:13 (in press).
Section
Pharmacological
Management
CHAPTERS
11. Traditional Oral Antidiabetic Drugs in Ramadan
12. Incretin-based Therapies and Fasting during Ramadan
13. Type 1 Diabetes Mellitus and Fasting during Ramadan
14. Insulin in Type 2 Diabetes Mellitus
Chapter
11
Abstract
The Holy Ramadan is a month of fasting and feasting. The Ramadan fast is observed by a large section
of Muslims with diabetes mellitus; more than 50 million people with diabetes are estimated to fast
during Ramadan globally. In general, oral hypoglycemic agents that act by decreasing peripheral
insulin resistance, like metformin are preferred because of their low hypoglycemic potential. The older,
long acting SUs like glibenclamide should be avoided because of the increased risk of hypoglycemia,
whereas the newer SUs like gliclazide MR or glimepiride can be safely used during Ramadan. Given
their widespread use and relatively low cost, these newer generation SUs may be used, albeit with
caution. To lessen the complications faced by diabetic patients who fast during Ramadan, health
professionals should aim to educate them about safe fasting, not only before and during Ramadan,
but also at follow-up.
INTRODUCTION
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Section 3: Pharmacological
Chapter 11: Traditional
Management
Oral Antidiabetic Drugs in Ramadan
96
Insulin Secretagogues
Insulin secretagogues are substances that stimulate or trigger a secretion or release
of insulin from pancreatic -cells. There are two classes of oral hypoglycemic agents
(OHAs) which stimulate release of insulin from -cells: the SU and meglitinides.
Sulfonylureas
Sulfonylureas are the oldest class of oral hypoglycemic agents and are in use for more
than 70 years. They were accidentally discovered by Marcel Janbon during World War
II, when he encountered some unexplained deaths in typhoid patients, who would
present with hypoglycemic symptoms and seizures after receiving sulphonamides.5
Their discovery was further confirmed by French physiologist, Auguste Loubatires
who observed that repeated oral administration of sulfonamide, 2254RP caused
hypoglycemia and convulsions in experimental animals. These hypoglycemic
sulfonamides were later named as SU.
Pharmacology
The mechanism of SU remained unclear till 1968 when it was shown that SU depolarize
the pancreatic -cell and stimulate electrical activity.6 Later on it was shown that SU
receptor is a component of the adenosine triphosphate (ATP)-sensitive potassium
(K+ATP) channel in the pancreatic -cell and their binding leads to inhibition of K+ATP
channels; the ensuing cell depolarization leads to calcium influx and stimulation
of insulin secretion.7 Sulfonylureas act independent of blood glucose levels but as
expected, are useful only in patients having some -cell function. Wide presence of
SU receptor in various tissues suggests that SU could be having extrapancreatic effects
as well, but the clinical importance of these effects is negligible.8
For several decades, after their introduction into clinical practice, SUs have been
the mainstay of the pharmacologic management of T2DM. In fact, SU are among the
most widely used drugs for the treatment of T2DM. Older SU like acetohexamide,
chlorpropamide and tolbutamide are called first generation SU, whereas so called
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Management
Oral Antidiabetic Drugs in Ramadan
97
Elimination
Half-life (h)
Route of
elimination
Usual daily
dose (mg)
Chlorpropamide
36 (2472)*
Urine, 8090%
250500
Once
Tolbutamide
4.5 (1416)
Urine, 7585%
1,0002,000
Once or divided
Glipizide
2.5 (1416)
Urine, 80%
2.510
Once or divided
Glibenclamide
(Glyburide)
2.510
Once
Gliclazide
10.4 (24)
40240
Once or divided
Glimepiride
9.2 (24+)
Urine, 60%
Feces, 40%
2.04.0
Once
Repaglinide
0.54.0
Nateglinide
1.5 (4.0)
Urine, 83%
60120
6.2 (24+)
Urine, 100%
1,0002,500
Once or divided
15.030.0
Once or divided
25100
First generation SU
Second generation SU
Meglitinides
Biguanides
Metformin
Thiazolidinediones
Pioglitazone
3-7 (24+)
Urine, 1530%
Bile
-Glucosidase Inhibitors
Acarbose
2.0
Feces, 51%
Urine, 34%
Adverse Reactions
Sulfonylureas are generally well tolerated, their main adverse effects being
hypoglycemia and weight gain. Because of their potential for causing -cell exhaustion
in the long run, and concerns regarding their cardiovascular safety (especially of
older agents like glibenclamide), the use of SU has fallen considerably with time. The
continued introduction of newer, safer, and effective classes of antidiabetic drugs
has further added to decline. However, in real terms, very few episodes of major
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Meglitinides
The meglitinides, repaglinide and nateglinide, are short-acting glucose-lowering
drugs for therapy of patients with T2DM or in combination with insulin sensitizers
like metformin. Though structurally different than SU, their action is similar to SUs,
i.e. by regulating ATP-dependent potassium channels in pancreatic -cells, thereby
increasing insulin secretion. However, meglitinides exert their effects via different
receptors. Their clinical efficacy and side effect profile is similar to that of the SU. The
usual daily dose of meglitinides is shown in Table 1.
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has been subject of many studies during Ramadan. In one of the earliest such studies
conducted in Malaysia, 235 sulfonylurea treated patients were randomized to receive
either repaglinide or glibenclamide 6 weeks before Ramadan till 4 weeks after
Ramadan.18 During Ramadan, patients changed their eating pattern to two meals daily,
repaglinide twice day (pre-prandial), and glibenclamide, once or twice daily. Though
both treatments were equally well-tolerated, the authors observed that hypoglycemic
events were significantly lower in the repaglinide group than the glibenclamide group
(2.8% vs. 7.9%; P < 0.001). Besides lesser hypoglycemias, blood glucose levels were also
better in repaglinide group with significant improvement in mean serum fructosamine
concentration, compared to glibenclamide group.18 Subsequent studies also showed
that repaglinide was safe and effective during Ramadan fasting.14,19,20
Some studies have tried to compare safety and efficacy of various OADs in general,
though there have not been any large head-to-head trials during Ramadan. In the
GUIDE study, a double-blind comparison of once daily gliclazide MR and glimepiride
in T2DM patients, gliclazide MR was found to cause fewer confirmed hypoglycemic
episodes as compared to glimepiride (3.7% versus 8.9%).21 In another study,
conducted to compare the treatment efficacy between repaglinide and glimepiride
during Ramadan fasting, 41 patients were randomized to receive either repaglinide or
glimepiride.22 No statistically significant difference in the incidence of hypoglycemia
or glycemic variability was observed in the two groups, and the authors concluded
that glimepiride may offer an advantage over repaglinide during the Ramadan
fasting because of its longer duration of action.22 Meglitinides, the short acting
insulin secretagogues (repaglinide and nateglinide) have short duration of action and
as such are useful in patients with Type 2 diabetes during Ramadan fasting. In the
above mentioned study by Mafauzy et al.18 the use of repaglinide was associated with
a lower risk of hypoglycemia; 0.03 hypoglycemic events per patient per month were
observed within repaglinide group compared to 0.05 events per patient per month in
the glibenclamide group.
Biguanides
Biguanides (Metformin), the only bigaunide presently available for use, is the most
widely prescribed medication in the pharmacological management of T2DM.
Though its main metabolic action appears to be upon the liver, the therapeutic use of
metformin has been ignited by the identification of its pleiotropic actions on several
tissues, which are affected by insulin resistance.23 The scientific utilization of formin
sisters (phenformin, metformin and buformin) became well-known in the 1950s, but
the so called association of biguanides with lactic acidosis in the 70s pulled them down
and they were wrenched from the industry.24 Though metformin was accepted for the
therapy of hyperglycemia in Europe (England) as early as 1958, it was not established
in the United States until 1995.
Pharmacology
Metformin is an insulin sensitizer. Though not very clear, the main action of metformin
lies in activating AMP-activated protein kinase (AMPK)an important enzyme
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that plays essential role in bodys energy balance.25 Metformin acts by decreasing
hepatic glucose production and intestinal glucose absorption, and improves insulin
sensitivity. The usual dose of metformin is 10002500 mg/day. It has a half-life is
6.2-hour (plasma); it is not metabolized and is excreted unchanged in urine (Table 1).
Adverse Reactions
Common reactions to metformin are mainly gastrointestinal, like, anorexia, nausea/
vomiting, indigestion, flatulence, abdominal discomfort and diarrhea. Other side
effects include headache, metallic taste in mouth, and megaloblastic anemia. Lactic
acidosis is often related to metformin, though there is no evidence at present that
metformin is associated with an increased risk for lactic acidosis when prescribed
under the study conditions.26 However, the drug is contraindicated in patients with
renal dysfunction with serum creatinine > 1.4 mg/dL (women) or 1.5 (men). Other
contraindications to metformin use include conditions predisposing to lactic acidosis
like hypoxia, dehydration, sepsis, surgery, congestive heart failure (CHF), metabolic
acidosis, diabetic ketoacidosis or chronic liver disease.
Thiazolidinediones
The TZDs, also known as glitazones, were introduced in the late 1990s. Troglitazone,
the first drug in this class to be marketed, was withdrawn from the market due to an
increased incidence of drug-induced hepatitis. Another TZD, Rosiglitazone was also
withdrawn from the market due to an increased risk of cardiovascular events, though it
is available in United States under selling restrictions. Pioglitazone, the only available
TZD in India, is also under debate due to several potential side effects.
Pharmacology
The insulin-sensitizing TZDs, are selective ligands of the nuclear transcription factor
peroxisome-proliferatoractivated receptor (PPAR).29 The mechanism by which
TZDs exert their effect is not fully understood, but they act on adipose tissue, muscle,
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and liver to increase glucose utilization and decrease glucose production. The efficacy
of the TZDs as monotherapy for the treatment of Type 2 diabetes is similar to that of
metformin; their cost and side effects make them less appealing as initial therapy.
Though one can give up to 45 mg of pioglitazone per day, the usual daily dose is
1530 mg (Table 1).
Adverse Effects
Common reactions to TZDs are include headache, edema, weight gain and dilutional
anemia. However, the serious adverse effects that are of concern include CHF,
hepatotoxicity, diabetic macular edema, fractures (in female patients) and bladder
cancer (with prolonged use). Although TZDs seem to improve many cardiovascular
risk factors, the data demonstrating their ability to decrease cardiovascular events are
unimpressive. As far the risk of hypoglycemia is concerned, TZDs are not independently
associated with hypoglycemia, though they can increase the hypoglycemic effects of
other hypoglycemic drugs.
Adverse Effects
Alpha-glucosidase inhibitors are not associated with any systemic adverse effects but
cause frequent mild to moderate GI side effects particularly flatulence. The risk of
hypoglycemia with AGIs is very low.32
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During Ramadan*
No change needed
Modifying the time and intensity of physical
activity should be discussed with the patient
Sulfonylureasglibenclamide, once or
twice daily.
* For all patients fasting during Ramadan, ensure adequate fluid intake.
Abbreviations: AGI-glucosidase inhibitor; OADsOral antidiabetic drugs; SUSulfonylureas;
TZDThiazolidinedione
Source: Adapted from Suliman M, Abdu T, Elhadd T, et al. Diabetes and fasting in Ramadan: Can we provide
evidence-based advice to patients? Sudan Med J. 2010:46(1):4-14.
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the usual morning dose with the Iftar. Slow release or extended release metformin
formulations (SR/XR) are usually well tolerated. These may be a better choice in
fasting diabetic patients who are controlled on metformin and can be taken once
daily after the Sehri. For those on AGIs like acarbose or voglibose, it is good enough to
continue with the prescribed doses of these drugs. To lessen the complications faced
by diabetic patients who fast during Ramadan, health professionals should aim to
educate them about safe fasting, not only before and during Ramadan, but also at
follow-up.
REFERENCES
1. Akbani MF, Saleem M, Gadit WU, et al. Fasting and feasting safely during Ramadan in the
patient with diabetes. Practical Diabetes Int. 2005;22(3):100-4.
2. Salti I, Benard E, Detournay B, EPIDIAR study group, et al. A population based study of
diabetes and its characteristics during the fasting month of Ramadan in 13 countries:
results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study.
Diabetes Care. 2004;27:2306-11.
3. Hui E, Bravis V, Hassanein M, et al. Management of people with diabetes wanting to fast
during Ramadan. BMJ. 2010;340:1408-11.
4. Zantar A, Azzoug S, Belhimer F, et al. Diabetes and Ramadan. Presse Med. 2012;
41(11): 1084-8.
5. Loubatires-Mariani MM. The discovery of hypoglycaemic sulfonamides. J Soc Biol. 2007;
201(2):121-5.
6. Dean PM, Matthews EK. Electrical activity in pancreatic islet cells. Nature.
1968;219(5152):389-90.
7. Aguilar-Bryan L, Nichols CG, Wechsler SW, et al. Cloning of the beta-cell high-affinity
sulfonylurea receptor: a regulator of insulin secretion. Science. 1995;268:423-6.
8. Bressler R, Johnson DG. Pharmacological regulation of blood glucose levels in non-insulindependent diabetes mellitus. Arch Intern Med. 1997;157:836-48.
9. McCulloch DK (2013). Sulfonylureas and meglitinides in the treatment of diabetes
mellitus. [online] Available from http://www.uptodate.com. [Accessed May,2013)
10. Shorr RI, Ray WA, Daugherty JR, et al. Incidence and risk factors for serious hypoglycaemia
in older persons using insulin or sulfonylureas. Arch Intern Med. 1997;157:1681-6.
11. Belkhadir J, El-Ghomari H, Klocker N, et al. Muslims with noninsulin-dependent diabetes
fasting during Ramadan: Treatment with glibenclamide. BMJ. 1993;307:292-5.
12. Schernthaner G, Grimaldi A, Di Mario U, et al. GUIDE study: Double-blind comparison
of once-daily gliclazide MR and glimepiride in type 2 diabetic patients. Eur J Clin Invest.
2004;34:535-42.
13. Rendell M. The role of sulphonylureas in the management of type 2 diabetes mellitus.
Drugs. 2004;64:1339-58.
14. Sari R, Balci MK, Akbas SH, et al. The effects of diet, sulfonylurea, and repaglinide therapy
on clinical and metabolic parameters in type 2 diabetic patients during Ramadan. Endocr
Res. 2004;30(2):169-77.
15. Zargar AH, Siraj M, Jawa AA, et al. Maintenance of glycaemic control with the evening
administration of a long acting sulphonylurea in male type 2 diabetic patients undertaking
the Ramadan fast. Int J Clin Pract. 2010;64(8):1090-4.
16. Mguil M, Ragala MA, El Guessabi L, et al. Is Ramadan fasting safe in type 2 diabetic
patients in view of the lack of significant effect of fasting on clinical and biochemical
parameters, blood pressure, and glycemic control? Clin Exp Hypertens. 2008;30(5):339-57.
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17. The Glimperide in Ramadan (GLIRA) Study Group. The efficacy and safety of glimepiride
in the management of type 2 diabetes in Muslim patients during Ramadan. Diabetes Care.
2005;28:421-2.
18. Mafauzy M. Repaglinide versus glibenclamide treatment of type 2 diabetes during
Ramadan fasting. Diabetes Res Clin Pract. 2002;58(1):45-53.
19. Johansen OE, Birkeland KI. Defining the role of repaglinide in the management of type 2
diabetes mellitus: a review. Am J Cardiovasc Drugs. 2007;7(5):319-35.
20. Bakiner O, Ertorer ME, Bozkirli E, et al. Repaglinide plus single-dose insulin glargine: a
safe regimen for low-risk type 2 diabetic patients who insist on fasting in Ramadan. Acta
Diabetol. 2009;46(1):63-5.
21. Schernthaner G, Grimaldi A, Di Mario U, et al. GUIDE study: Double-blind comparison
of once-daily gliclazide MR and glimepiride in type 2 diabetic patients. Eur J Clin Invest.
2004;34:535-42.
22. Anwar A, Azmi KN, Hamidon BB, et al. An open label comparative study of glimepiride
versus repaglinide in type 2 diabetes mellitus Muslim subjects during the month of
Ramadan. Med J Malaysia. 2006;61(1):28-35.
23. Palomba S, Falbo A, Zullo F, et al. Evidence-based and potential benefits of metformin
in the polycystic ovary syndrome: a comprehensive review. Endocrine Reviews. 2009;
30:1-50.
24. Wood AJ. Drug therapy metformin. N Engl J Med. 1996;334:574-9.
25. Musi N, Hirshman MF, Nygren J, et al. Metformin increases AMP-activated protein kinase
activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002;51:2074-81.
26. Salpeter SR, Greyber E, Pasternak GA, et al. Risk of fatal and nonfatal lactic acidosis with
metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010;(4):CD002967.
doi: 10.1002/14651858.CD002967.pub4.
27. Bolen S, Feldman L, Vassy J, et al. Systematic review: Comparative effectiveness and safety
of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147:386-99.
28. Bonakdaran SH, Khajeh-Dalouie M. The effects of fasting during Ramadan on glycemic
excursions detected by continuous glucose monitoring system (CGMS) in patients with
type 2 diabetes. Med J Malaysia. 2011;66(5):447-50.
29. Yki-Jrvinen H. Thiazolidinediones. N Engl J Med. 2004;351(11):1106.
30. Vasan S, Thomas N, Bharani, et al. A double-blind, randomized, multicenter study
evaluating the effects of pioglitazone in fasting Muslim subjects during Ramadan. Int J
Diabetes Dev Ctries. 2006;26:70-6.
31. Meneilly GS, Ryan EA, Radziuk J, et al. Effect of acarbose on insulin sensitivity in elderly
patients with diabetes. Diabetes Care. 2000;23(8):1162-7.
32. Pan C, Yang W, Barona JP, et al. Comparison of vildagliptin and acarbose monotherapy
in patients with type 2 diabetes: A 24-week, double-blind, randomized trial. Diabet Med.
2008;25:435-41.
33. Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes
during Ramadan: update 2010. Diabetes Care. 2010;33(8):1895-902.
34. Suliman M, Abdu T, Elhadd T, et al. Diabetes and fasting in Ramadan: Can we provide
evidence-based advice to patients? Sudan Med J. 2010:46(1):4-14.
35. Salti I, Bnard E, Detournay B, et al. EPIDIAR study group. A population-based study of
diabetes and its characteristics during the fasting month of Ramadan in 13 countries:
Results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study.
Diabetes Care. 2004;27:2306-11.
Chapter
12
Abstract
Incretin hormones are intestinally derived peptides that play major role in the normal regulation of
glucose homeostasis. Incretin effect is impaired in Type 2 diabetes, leading to development of new
therapeutic strategies aimed at redressing this abnormality. These strategies include administration of
inhibitors of dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for of rapid endogenous incretin
degradation, and the use of glucagon-like peptide-1 (GLP-1) receptor analogues. Hypoglycemia is
a well-known risk associated with the daytime fasting required during Ramadan, especially for individuals with Type 2 diabetes. DPP-4 inhibitors and GLP-1 analogues stimulate insulin secretion and
inhibit glucagon secretion in a glucose-dependent manner and carry no intrinsic risk of hypoglycemia.
Therefore, such therapies may be suitable for Type 2 diabetic patients who fast Ramadan. However,
few current data related to the use of DPP-4 inhibitors during Ramadan are available. In addition,
there are no published studies on the use of GLP-1 analogs during Ramadan. Although preliminary
clinical studies provide clear and interesting benefits of the use of incretin-based therapies during
Ramadan, further and larger studies are needed to draw firm conclusions.
INTRODUCTION
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(DPP-4). Thus, the glucose-lowering activity of GLP-1 is relatively short lived, with a
circulating half-life of less than 2 minutes.5
The therapeutic arsenal in Type 2 diabetes has expanded in recent years with the
addition of incretin-based antidiabetic agents. Two approaches have thus emerged
to increase incretin action: administration of injectable GLP-1 mimetics or analogs,
consisting in molecules that are DPP-4 resistant, or administration of inhibitors of
DPP-4, able to enhance endogenous GLP-1 and GIP.6 Major similarities and points
of distinction between the two classes of incretin-based therapies are summarized in
Table 1.7
During the holy month of Ramadan, Muslims observe a daytime fast and abstain
from eating and drinking. Both the act of fasting and the use of antihyperglycemic
therapy may increase the risk of hypoglycemia. The EPIDAR (Epidemiology of
Diabetes and Ramadan) study noted a 7.5-fold increase in the incidence of severe
hypoglycemia during Ramadan in patients with Type 2 diabetes.8 To minimize
GLP-1 analogs
DPP-4 inhibitors
Mode of action
Usage
Administration
Sc injection (pen)
Oral (tablet)
Reduction in HbA1c
~11.5%
~0.51%
Beta-cell function
Possibly improved
Possibly improved
Extraglycemic
efits
Hypoglycemia
Very low-risk
Very low-risk
Weight
Reduction
Neutral
GI adverse effects
Frequent
dependant
limited)
Gastric emptying
Pancreatitis
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Figure 1: Physiological effects of the incretin hormone GLP-1. GLP-1 administration exerts diverse biological actions on a number of human target organs, such as the pancreas, heart, brain, liver, stomach,
muscle and adipose tissue. The actions of GLP-1 in liver, fat, and muscle most likely occur through
indirect mechanisms (dotted arrows)11
Abbreviation: GLP-1Glucagon-like peptide-1
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110
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Figure 2: Mean (SD) glycated hemoglobin (HbA1c) at baseline and following Ramadan fasting in vildagliptin group (n = 20) and SU (n = 32) group. Mean between-group difference (vildagliptin cohort minus SU cohort) in HbA1c change from baseline was - 0.5% (p= 0.02)28.
Abbreviation: SUSulfonylurea
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Figure 3: Proportion of patients reporting symptomatic hypoglycemia during Ramadan overall and
by country29
*Number of patients experiencing event number of patients overall or in each country by treatment (%)
112
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Flow chart 1: Suggested role of incretin-based therapies in the management of type 2 diabetic patients who wish to fast Ramadan
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Exenatide and liraglutide injections have a potential for safe use during Ramadan,
primarily because their reduced risk of hypoglycemia. This low-risk of hypoglycemia
may offer advantages regarding medication adherence during Ramadan; as
hypoglycemia is a major problem for antidiabetic medication adherence. However,
hypoglycemia can still occur when GLP-1 receptor agonist therapy is combined with
an insulin secretagogue such as a SU. Therefore, insulin secretagogue dose should be
adjusted when it is combined with a GLP-1 analog.36
In a head-to-head comparison of liraglutide and exenatide in combination with
metformin and/or SU, liraglutide reduced HbA1c by significantly more than exenatide
(1.12 0.08% vs. 0.79 0.08%, p < 0.0001).37 Others studies have also shown that
liraglutide is associated with less pronounced gastrointestinal side effects compared
with exenatide.38,39 As yet, there are no published reports on the use of GLP-1 analogs
during Ramadan.
CONCLUSION
Current data indicates that incretin-based antidiabetic agents may have a role to play
in the management of Muslim patients with diabetes during Ramadan, particularly
to reduce their risk of hypoglycemia during the long daytime fasting periods.
Furthermore, patients who fasted showed very good adherence to these drugs making
them an attractive therapeutic option for the safe management of fasting. Suggested
role of incretin-based therapies in the management of Type 2 diabetic patients during
Ramadan is provided in Flow chart 1. Further and larger studies are needed to draw
firm conclusions.
ACkNOwLEDGMENTS
We are thankful to Dr Basma Ben Naceur, Mohamed Habib Sfar, Nadia Charfi, Fatma
Mnif, Mohamed Dammak, Nabila Rekik, Mohamed Abid for their contribution in the
preparation of this manuscript.
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with type 2 diabetes treated with sitagliptin or a sulphonylurea during Ramadan: a
randomised trial. Int J Clin Pract. 2011;65:1132-40.
31. Aravind SR, Ismail SB, Balamurugan R, et al. Hypoglycemia in patients with type 2 diabetes
from India and Malaysia treated with sitagliptin or a sulfonylurea during Ramadan: a
randomized, pragmatic study. Curr Med Res Opin. 2012;28:1289-96.
32. Garber AJ. Incretin therapypresent and future. Rev Diabet Stud. 2011;8:307-22.
33. Gallwitz B, Guzman J, Dotta F, et al. Exenatide twice daily versus glimepiride for prevention
of glycaemic deterioration in patients with type 2 diabetes with metformin failure
(EUREXA): an open-label, randomised controlled trial. Lancet. 2012;379:2270-8.
34. Drab SR. Clinical studies of liraglutide, a novel, once-daily human glucagon-like peptide-1
analog for improved management of type 2 diabetes mellitus. Pharmacotherapy.
2009;29:43S-54S.
35. Garber A, Henry R, Ratner R, et al. Liraglutide versus glimepiride monotherapy for type
2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III , double-blind, paralleltreatment trial. Lancet. 2009;373:473-81.
36. Almaatouq MA. Pharmacological approaches to the management of type 2 diabetes in
fasting adults during Ramadan. Diabetes Metab Syndr Obes. 2012;5:109-19.
37. Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day
for type 2 diabetes: a 26-week randomised, parallel group, multinational, openlabel trial
(LEAD-6). Lancet. 2009;374:39-47.
38. Kendall DM, Cuddihy RM, Bergenstal RM. Clinical application of incretin-based therapy:
therapeutic potential, patient selection and clinical use. Am J Med. 2009;122:S37-50.
39. Edwards KL, Stapleton M, Weis J, et al. An update in incretin-based therapy: a focus on
glucagon-like peptide-1 receptor agonists. Diabetes Technol Ther. 2012;14:951-67.
Chapter
13
Abstract
Fasting during Ramadan is fraught with multiple medical problems for patients with T1DM. The risks
of fasting include hypoglycemia, hyperglycemia, DKA, and dehydration. The Ramadan fast typically
consists of a fasting period which can extend up to 12 hours in summer and 89 hours in winter.
Once the fast is broken, it is followed by a heavy evening meal. The meals are also traditionally rich in
fats and carbohydrates. In patients with T1DM, the normal metabolic mechanisms become modified
by various factors like hypoglycemia unawareness and autonomic neuropathy leading to lack of
epinephrine rise during episodes of hypoglycemia and failure of glucagon secretion to increase, during
hypoglycemia. Excessive decrease of insulin dose during fasting can precipitate hyperglycemia and
diabetic ketoacidosis (DKA) and a relatively higher dose can lead to hypoglycemia. However, fasting
during Ramadan for patients with T1DM is feasible, provided good pre-Ramadan glycemic control is
initiated, appropriate education and preparation for the fasting period is imparted and coordination
is maintained between the health care provider and the patient is maintained throughout the fasting
period and also subsequently.
INTRODUCTION
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1995 defined suitable criteria for fasting and exempted people with Type 1 diabetes
from fasting. However, a sense of appreciation of their religious responsibilities and a
desire to fast along with other adherents of the faith has ensured that a large majority
of Muslims with Type 1 diabetes mellitus (T1DM) continue to fast during Ramadan.
COMPLICATIONS OF FASTING
Fasting during Ramadan is fraught with multiple medical problems for patients
with T1DM. The risks of fasting include hypoglycemia, hyperglycemia, DKA and
dehydration.4
Hyperglycemia
Hyperglycemia is one of the most common problems observed during this month.
A fear of hypoglycemia on part of both the doctors and the patients, coupled with
carbohydrate and calorie-rich meals, associated with an abrupt change in meal times
and use of insulin contributes to this hyperglycemia. Water is also proscribed during
the fast throughout this month. While fasting, eating and drinking are exclusively at
night. Further, the management of children with diabetes who choose to fast during
Ramadan, also poses a challenge, as the majority of guidelines and data on safety and
metabolic impact of fasting are based on practice and studies on adult population.
The EPIDIAR (Epidemiology of Diabetes and Ramadan) study1 reported a five-fold
increase in the incidence of severe hyperglycemia (requiring hospitalization) and
an approximate three-fold increase in the incidence of severe hyperglycemia with or
without ketoacidosis in patients with Type 1 diabetes. However, there is no information
linking yearly episodes of a month long fast and diabetes-related complications.
Diabetic Ketoacidosis
Patients with Type 1 diabetes, who fast during Ramadan are at a greater risk for
developing DKA. This is plausible in the setting of pre-fast poor control and compliance,
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carbohydrate-rich meals, the tendency to reduce insulin doses for fear of hypoglycemia
and in the setting of infection. However, data which supports the increased incidence
of DKA during the Ramadan fasting is scarce. In fact, studies by Kadika5, Abusreiwil6
and Rafik7 have reported rates of incidence of DKA during Ramadan fasting, which are
similar to the general population incidence rates. However, given the increased risk
factors for DKA during fasting and the high morbidity and mortality associated with
DKA, appropriate education about recognizing DKA and vigilance for its symptoms
must be strictly enforced during Ramadan fasting.
Dehydration
Multiple factors are responsible for dehydration during fasting, including a restriction
on fluid intake while fasting, osmotic diuresis due to hyperglycemia, fasting during
summer and increased physical activity and associated sweating. Dehydration,
especially when severe, can manifest as postural dizziness, orthostatic hypotension
leading to falls and fractures, especially in the older people, and the most dreaded
complication of thrombosis. Dehydration precipitates a hypercoagulable state due to
contraction of intravascular volume and increase in the viscosity of blood. Diabetes
itself is a prothrombotic state due to decreased fibrinolysis and endogenous anticoagulants and the rise in a few clotting factors. This thrombotic state can manifest
as a cerebrovascular accident, myocardial infarction or even as retinal vein occlusion.
Hypoglycemia
Fasting can precipitate hypoglycemia due to a reduction in oral intake. The impact
of fasting during Ramadan on incidence of hypoglycemia and mortality is not
well known. The EPIDIAR study1 found that the change in eating patterns during
Ramadan increased the risk of severe hypoglycemia 4.7-fold (from 3 to 14 events per
100 people per month) in Type 1 diabetes. Further, severe hypoglycemia was probably
under-reported in this study, because only episodes requiring hospitalization
were considered. Another study by Loke SC et al.8 found that relative risk (RR) of
hypoglycemia of 1.60 during Ramadan fasting, compared with a non-fasting period of
equivalent length. Good metabolic control [glycated hemoglobin (HbA1C) < 8 percent)]
and old age (> 60 years) increased RR more than twice, while taking breakfast prior to
fasting reduces RR to less than half. These RR are lower than what have been reported
by EPIDIAR.1 Hypoglycemia is of special concern in children and adolescents due
to its neurocognitive impact. Some of the factors which can influence the severity of
hypoglycemia while fasting are: the age of patient with T1DM, duration of diabetes,
prior glycemic control, level of diabetes education and the type of insulin being used.
In a study by Kadiri et al.9 when lispro was compared with regular insulin in T1DM
patients on a Ramadan fast incidence of hypoglycemia (15 episodes for lispro vs. 31
for regular insulin), frequency of hypoglycemia (0.7 0.19 episodes for lispro vs. 2.26
0.36 episodes/patient/30 days for regular insulin) and nocturnal hypoglycemia (5
episodes for lispro vs. 27 for regular insulin) were lower with lispro, while compliance
with recommended time of insulin injection was better, thus underlining the
advantages of rapid acting analogs over regular insulin in fasting patients with T1DM.
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119
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120
Exercise
While some physical activity during the day is encouraged, it should not be overdone,
especially in the late afternoon, as it can precipitate hypoglycemia and also lead to
dehydration. Physical activity during the prayers should also be factored into the
quantum of total daily exercise.
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Flow chart 1: Approach to a Type 1 diabetes mellitus patient planning for Ramadan fast
Insulin Regimens
Several insulin regimens have been proposed by various studies and guidelines.
When prescribing a regimen, a balance should be sought between safety, efficacy,
cost of therapy and patient acceptability. Individualization of regimens based on
the pre-Ramadan glycemic record can be helpful. Some of the regimens which can
be used are mentioned in Table 3 and a few caveats regarding insulin therapy in
Table 4.12,13
Insulin Pumps
The increasing availability and rising affordability of insulin pumps have provided
a new option for managing T1DM during Ramadan. While studies about pump
therapy are limited, a few studies have been published in the past 23 years, all of
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Basal-bolus
conventional***/2
Twice daily
regimen***
LA analog +
Regular insulin**
Insulin pump*
Single dose of
long-acting
analog in late
evening with two
doses of prandial
short-acting
analog.
Correcting doses
of short-acting
analog as
required, based
on SMBG
To use
morning dose
of premix /split
mix regimen
before evening
meal and use
only shortacting insulin
at 0.10.2 u/
kg before predawn meal
Single dose of
long-acting
analog in late
evening with two
doses of prandial
regular insulin.
Useful when
early morning
hypoglycemia
is to be avoided
and affordability
precludes short
acting analog
Reduce basal
infusion rate
and increase
bolus dose
prior to
evening and
morning
meals.
Table 4: Caveats regarding insulin therapy and SMBG during Ramadan fast13
Basal insulin should be reduced by up to 20 percent of pre-dose
If using premix, 50/50 can be used instead of 30/70 to avoid post-prandial hyperglycemia
As a starting point, transfer morning pre-meal dose to evening and take half of pre-dinner
dose before the dawn meal. Titrate according to SMBG
Adjust insulin doses every 3 days or more frequently, if required
Insulin therapy should be supported by frequent SMBG
Blood glucose levels should be monitored half an hour before and 2 hours after evening
meal, 2 hours after pre-dawn meal, at mid-day and whenever symptoms suggestive of
hypoglycemia or hyperglycemia occur
End fast if blood glucose < 60 mg/dL or > 300 mg/dL
Avoid fasting on sick days
Use of carbohydrate counting and correction doses of short acting insulin as required
Abbreviation: SMBGSelf-monitoring of blood glucose
which have endorsed the efficacy and safety of insulin pumps during Ramadan. A
pump is very useful in balancing the risk of hypoglycemia while fasting and the
hyperglycemia which can set in after the heavy evening meal, by timely adjustments
of basal and prandial insulin delivery through pump. In a study by Al Baker et al.14
T1DM patients on insulin pump, when compared to patients on multiple daily insulin
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injections (MDII) or premix insulin, were able to fasting period able to complete their
fasting with minimal episodes of mild hypoglycemia (two episodes per patient), no
episodes of hypoglycemia requiring assistance and no emergency room (ER) visits.
They also had better biochemical profiles than patients on premix insulin and profiles
comparable to patients on MDII. In another study by Khalil et al.15 patients on pump
had no change in basal insulin requirements from the pre-fasting period, had very
few episodes of minor hypoglycemia which were easily managed by titration of doses
and no episodes of major hypoglycemia, thus underlining the advantages of pump
therapy. However, to use a pump during Ramadan, the patient needs to be educated
about the pump, motivated to monitor blood glucose frequently and should also be
able to afford pump therapy. If these limitations are overcome, insulin pumps seem to
provide the best possible solution for control of sugars during Ramadan fasting with
minimal complications.
FUTURE PERSPECTIVES
Smart Insulins
These comprise a new type of insulin delivery system, based on nanotechnology. These
glucose-responsive controlled insulin delivery systems are based on the agglomerated
vesicle technology (AVT), which is a chemically cross-linked agglomerate of liposomes
loaded with insulin.16 The break-up of these chemical cross links can be initiated by
high blood glucose levels, thus releasing insulin from the agglomerate and restoration
of blood glucose to normal levels. The quantity of insulin released is proportional to
the blood glucose level and thus, the hypoglycemia generally associated with insulin
use can be avoided. Initially, a lectin, cancavalinA was used as a cross-linker,16 but
due to its toxicity and inflammatory effects, it was discarded and boronic acids are now
being explored. In addition, to being non-toxic and noninflammatory, more so when
conjugated with lipid polyethylene glycol (PEG), boronic acids17 have also been found
to have a basal untriggered release of insulin, a property not found with concavalin-A.
This helps to avoid a build-up of cross-linked insulin in the body and also ensures
a basal insulin release. These insulins are at least a decade away from commercial
development, but have the potential to be useful for treatment while fasting during
Ramadan and in avoiding hypoglycemia.
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REFERENCES
1. Salti I, Benard E, Detournay B, EPIDIAR study group, et al. A population based study of
diabetes and its characteristics during the fasting month of Ramadan in 13 countries:
results of the epidemiology of diabetes and Ramadan.(EPIDIAR) study. Diabetes Care.
2004;27:2306-11.
2. International Meeting on Diabetes and Ramadan Recommendations. Edition of the
Hassan II Foundation for Scientific and Medical Research on Ramadan. Casablanca,
Morocco, FRSMR, 1995.
3. Al-Arouj M, Bouguerra R, Buse J, et al. Recommendations for management of diabetes
during Ramadan. Diabetes Care. 2005;28:2305-11.
4. Ahmad J, Pathan M, Jaleel MA, et al. Diabetic emergencies including hypoglycemia during
Ramadan. Indian J Endocr Metab. 2012;16:512-5.
5. Kadiki OA, Moawad SE, Khan ZA, et al. Diabetes mellitus and Ramadan. Garyounis Med
J. 1989;12:32-4.
6. Abusrewil SS, Turki HM, Osman F, et al. Ramadan fasting and diabetic control in
Adolescent and young Adults. Jamahiriya Med J. 2003;2:49-50.
7. Rafik E, Mohammad E, Hanan E. Incidence of Diabetic Ketoacidosis during Ramadan
Fasting in Benghazi-Libya. Oman Med J. 2009;24:99-102.
8. Loke SC, Rahim KF, Kanesvaran R, et al. A prospective cohort study on the effect of various
risk factors on hypoglycemia in Diabetes who fast during Ramadan. Med J Malayasia.
2010;65:3-6.
9. Kadiri A, Al-Nakhi A, El-Ghazali S, et al. Treatment of type 1 diabetes with insulin lispro
during Ramadan. Diabetes Metab. 2001;27:482-6.
10. Hui E, Bravis V, Hassanein M, et al. Management of people with diabetes wanting to fast
during Ramadan. BMJ. 2010;22:340. c3053. doi: 10.1136/bmj.c3053.
11. Bravis V, Hui E, Salih S, et al. Ramadan Education and Awareness in Diabetes (READ)
programme for Muslims with type 2 diabetes who fast during Ramadan. Diabetic
Medicine. 2010;27:327-31.
12. Pathan MF, Sahay RK, Zargar AH, et al. South Asian Consensus Guideline: Use of insulin in
diabetes during Ramadan. Indian J Endocr Metab. 2012;16:499-502.
13. Azad K, Mohsin F, Zargar AH, et al. Fasting guidelines for diabetic children and adolescents.
Indian J Endocr Metab. 2012;16:516-8.
14. AlBaker WI, Khamis A, Al-Hamayal AA. Efficacy and safety of insulin pump in type 1
diabetes during fasting time (Month of Ramadan). Global Advanced Research Journal of
Microbiology (ISSN: 2315-5116). 2013;2(1):1-6.
125
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15. Khalil AB, Beshyah SA, Abu Awad SM, et al. Ramadan fasting in diabetes patients on
insulin pump therapy augmented by continuous glucose monitoring: an observational
real-life study. Diabetes Technol Ther. 2012;14(9):813-8.
16. Karathanasis E, Bhavane R, Annapragada AV. Glucose-sensing pulmonary delivery of
human insulin to the systemic circulation of rats. Int J Nanomedicine. 2007;2(3):501-13.
17. Dasgupta I, Tanifum EA, Srivastava M, et al. Non inflammatory boronate based glucoseresponsive insulin delivery systems. PLoS One. 2012;7(1):e29585. doi: 10.1371/journal.
pone.0029585. Epub 2012 Jan 17.
18. Hari Kumar KV, Shaikh A, Prusty P. Addition of exenatide or sitagliptin to insulin in
new onset type 1 diabetes: A randomized, open label study. Diabetes Res Clin Pract.
2013;100(2):e55-8. doi: 10.1016/j.diabres.2013.01.020. Epub 2013 Mar 13.
19. Ellis SL, Moser EG, Snell-Bergeon JK, et al. Effect of sitagliptin on glucose control in adult
patients with Type 1 diabetes: a pilot, double-blind, randomized, crossover trial. Diabet
Med. 2011;28(10):1176-81. doi: 10.1111/j.1464-5491.2011.03331.x.
20. Sharifi F, Ghazi Saidi M, Mousavi Nasab N. Effects of Acarbose in Metabolic Control of
Patients. Int J Endocrinol Metab. 2008;1:13-9.
Chapter
14
Insulin in Type 2
Diabetes Mellitus
Altamash Shaikh, Manoj Chadha
Abstract
A significant proportion of diabetes patients fast in Ramadan and are either already on insulin
or may be started (naive), presenting a challenge for the management to the health care providers. This chapter emphasizes on the importance of prerequisite of insulin, its strategies, and role
of insulin in special populations like the pregnant lady and the elderly. Implementing insulin in
management through patients and their family members will provide a successful path towards
the unbroken barriers and complications of diabetes. Prevention of hypoglycemia is mainstay of
diabetes management in Ramadan. Monitoring of blood glucose for dose adjustment and prevention of glycemic excursions are dealt with. Insulin regimens should be tailored to meet individual
needs of a patient in Ramadan.
INTRODUCTION
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High-Risk
Moderate Risk
Well-controlled diabetes treated with short-acting insulin secretagogues.
Low-Risk
Well-controlled diabetes treated with lifestyle therapy, metformin, acarbose,
thiazolidinediones, and/or incretin-based therapies in otherwise healthy patients.
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Insulin initiation
Pre-Ramadan
During Ramadan
Bedtime only
Titrate fasting glucose
If the patient is on two premix insulin dose, 100 percent of the pre-Ramadan
morning dose of 2.33 premixed insulin may be given at Iftar and 50 percent of the
usual evening dose at Suhur, i.e. if patient is on 30 units in morning and 20 units at
dinner then give full 30 units at sunset meal (Iftar) and 10 units at sunrise meal (Suhur)
or If the patient is on basal bolus therapy, and takes two meals only in Ramadan. Then
this can be switched to basal plus regimen. To give one basal at evening meal, and a
short acting post-dawn meal (Suhur). Example: Basal insulin at sunset meal (Iftar)
and short acting at sunrise meal (Suhur).
If the patient is on basal bolus therapy, and takes three meals, i.e. dinner in addition
to above two meals, then an extra shot of rapid acting insulin is a must predinner to
avoid premorning hyperglycemia. Example: 20 percent reduced dose of basal insulin
at 10 pm, three short-acting insulin: First at sunset meal (Iftar), second dose at dinner
and third dose (50% of dinner dose) at sunrise meal (Suhur).
Few patients already on a premixed regimen, who choose to fast, should have their
regimen inversed. This is accomplished by giving the full morning dose at pre-sunset
meal. The usual evening dose in this category of patients can be reduced by half and
given at the pre-sunrise meal. Continuation of insulin this way has given better clinical
outcome in clinical practice (Table 2).
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Insulin continuation
Pre-Ramadan
During Ramadan
On basal insulin
At Iftar
At dinner
Half the dose at Suhur
Insulin optimization
Pre-Ramadan
During Ramadan
RI + 0 + RI
NPH + 0 + NPH
Evening dose
Morning dose
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Another way for optimization for patients on premix 30 twice daily, is to further
increase the sunset meal (Iftar) premix dose to cover the expectant postmeal glucose
excursion. This is due to the fact that sunset meal (Iftar) may be high in carbohydrate
content and may also be larger in quantity in some patients.
This reduces the chances of hypoglycemia and better yields glycated hemoglobin.
Example: Out of the 70 percent of the pre-Ramadan insulin dose: 60 percent as 1 daily
injection of basal insulin in the evening and 40 percent as short-acting insulin given
in 2 doses, 1 at Suhur and 1 at Iftar.
If on split insulin therapy,4 with short-acting and intermediate acting insulin twice
daily then morning doses of both can be given at sunset meal (Iftar) and dinner doses
of both should be made into half and given at sunrise meal (Suhur).
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Insulin Intensification
During Ramadan
Iftar
Dinner
Suhur
RI + RI + RI + NPH
Lunch dose
Evening dose
Basal portion
If patient is on NPH
NNight
During Ramadan
Metformin
During Ramadan
Liraglutide + insulin
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options. Exenatide twice daily dosage can be given pre-sunrise meal (Suhur) and
pre-sunset meal (Iftar). Long-acting exenatide once weekly doses can be given as
usual dose as prior to Ramadan. However, liraglutide once daily should be given at
sunset meal (Iftar) preferably without any change in dose.6 And insulin when basal,
can be given preferably at bedtime, whereas timing of other insulin regimen (twice
daily, basal plus, basal bolus, split-mixed regimen) can remain same, presently till
more evidence on their use is available.
As there are exceedingly rare chances of hypoglycemia with GLP-1 analog
combinations, frequent checking of blood glucose may be relaxed. This class of drug
can be used with renal or hepatic impairment, but gastrointestinal side effects does
exist.
Studies with the aim of investigating the use of GLP-1 analogs during Ramadan
are needed.
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Pre-Ramadan
During Ramadan
Basal plus
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monitoring is required. One limitation is the failure of pump or the infusion site with
resultant loss of glycemic control over just few hours.
Basal rate of pump needs to be adjusted in evening hours, and boluses more at
sunrise meal (Suhur) and sunset meal (Iftar). There is decrease in basal insulin up to
20 percent in day time. Pre-Ramadan evaluation, counseling, monitoring need not be
re-emphasized, even while using pumps.
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All patients should understand that they must always and immediately end their
fast if hypoglycemia (blood glucose of < 60 mg/dL [3.3 mmol/L]) occurs, since there
is no guarantee that their blood glucose will not drop further if they wait or delay
treatment.
The fast should be broken if blood glucose exceeds 300 mg/dL (16.7 mmol/L), and
urine ketones should be checked.4 However, in clinical practice if regular checking is
not done and; as hyperglycemia may be asymptomatic in some patients, this may not
be picked up. Patients should also avoid fasting on sick days.
SUMMARY
Fasting should be encouraged but with medical supervision. More counseling for
patients and more training for healthcare providers should be imparted, to strengthen
Action
2 hours post-Iftar
2 hours post-dinner
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Benefit
2 hours post-Iftar/dinner
DISCLAIMER
The authors received no funding and report no conflict of interest.
REFERENCES
1. Salti I, Benard E, Detournay B, et al. A population-based study of diabetes and its
characteristics during the fasting month of Ramadan in 13 countries. Diabetes Care.
2004;27(10):2306-11.
2. Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes
during Ramadan: update 2010. Diabetes Care. 2013;33(8):1895-902.
3. Fatim J, Karoli R, Chandra A, et al. Attitudinal determinants of fasting in type 2 diabetes
mellitus patients during Ramadan. J Assoc Physicians India. 2011;59:630-4.
4. Pathan MF, Sahay RK, Zargar AH, et al. South Asian Consensus Guideline: Use of
insulin in diabetes during Ramadan. Indian J Endocrinol Metab. 2012;16(4):525-7. doi:
10.4103/2230-8210.98003.
5. Bakiner O, Ertorer ME, Bozkirli E, et al. Repaglinide plus single-dose insulin glargine: a
safe regimen for low-risk type 2 diabetic patients who insist on fasting in Ramadan. Acta
Diabetologica. 2009;46(1):63-5. doi: 10.1007/s00592-008-0062-7. Epub 2008 Sep 30.
6. Pathan MF, Sahay RK, Zargar AH, et al. South Asian Consensus Guideline: Use of GLP-1
analog therapy in diabetes during Ramadan. Indian journal of endocrinology and
metabolism. Indian J Endocrinol Metab. 2012;16(4):525-7. doi: 10.4103/2230-8210.98003.
7. Mattoo V, Milicevic Z, Malone JK, et al. A comparison of insulin lispro Mix25 and human
insulin 30/70 in the treatment of type 2 diabetes during Ramadan. Diabetes research and
clinical practice. Diabetes Res Clin Pract. 2003;59(2):137-43.
8. Ismail NA, Olaide Raji H, Abd Wahab N, et al. Glycemic Control among Pregnant Diabetic
Women on Insulin Who Fasted During Ramadan. Iranian journal of medical sciences.
Iran J Med Sci. 2011;36(4):254-9.
9. Nor Azlin MI, Adam R, Sufian SS, et al. Safety and tolerability of once or twice daily neutral
protamine hagedorn insulin in fasting pregnant women with diabetes during Ramadan.
J Obstet Gynaecol Res. 2011;37:132-7.
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10. Ahmad J, Pathan MF, Jaleel MA, et al. Diabetic emergencies including hypoglycemia
during Ramadan. Indian journal of endocrinology and metabolism. Indian J Endocrinol
Metab. 2012;16(4):512-5. doi: 10.4103/2230-8210.97996.
11. Bravis V, Hui ES, et al. European implications of the READ (Ramadan focused Education
and Awareness in Diabetes) programme. Diabetologia. 2008;51(Suppl):S454.
12. Shaikh A. Family therapy in diabetes mellitus. IJEM. 2013;238:13 (in press).
Section
Special Situation in
Ramadan
CHAPTERS
15.
16.
17.
Chapter
15
Abstract
The holy month of Ramadan is one of the five main pillars of being a Muslim. Many experts have
opined that patients with Type 1 diabetes who fast during Ramadan are at a very high risk of developing complications, if the pattern and amount of their meal and fluid intake are markedly altered.
However, some experienced physicians believe that fasting during Ramadan is safe for patients with
Type 1 diabetes mellitus (T1DM) also, including adolescents and older children, if their glycemic
control is good. The factors which are important for healthy children above 12 years who wish to fast
during Ramadan are individualization, frequent monitoring of blood sugar during fast, nutrition,
exercise, breaking the fast if necessary, pre-Ramadan medical assessment and Ramadan-focused
patient education. Insulin-pump therapy may help in controlling blood glucose during fasting and
continuous insulin infusion can be modified and adjusted instantaneously to avoid hypoglycemia
and the necessity to break the fast.
INTRODUCTION
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Situation
15: in
Ramadan
Ramadan
Fasting in Children and Adolescents
144
PATHOPHYSIOLOGY OF FASTING
Fasting during Ramadan is not meant to cause excessive hardship on Muslims.
Nevertheless, many patients with diabetes insist on fasting during Ramadan. This, in
turn, creates a medical challenge for not only themselves, but also their health care
providers. It is very important for medical professionals to be aware of the potential
risks associated with fasting during Ramadan as well as the approaches to overcome
them.3
Feeding stimulates insulin secretion in healthy individuals and promotes the
storage of glucose in liver and muscle as glycogen. Fasting leads to hypoglycemia
and decreased secretion of insulin. It also leads to increased secretion of counterregulatory hormones like glucagon and catecholamines resulting in glycogenolysis
and gluconeogenesis.6 Prolonged fasting depletes glycogen stores resulting in
hypoinsulinemia, the first defence against hypoglycemia. This releases fatty acids
from adipocytes, which are oxidized to ketones. These can be used as fuel by the liver,
kidney, skeletal muscle, cardiac muscle, and adipose tissue. This is a vital step as it
ensures that brain and erythrocytes continue to get glucose for their metabolism.
In nondiabetic patients, the above processes are regulated by a delicate balance
between circulating levels of insulin and counter regulatory hormones that help to
maintain glucose concentrations in the physiological range. However, in diabetic
patients, insulin secretion is altered by the underlying pathophysiology and the
various antidiabetic drugs, to enhance or supplement insulin secretion.
Box 1: Risks associated with fasting in diabetic patients
Hypoglycemia
Hyperglycemia
Diabetic ketoacidosis
Dehydration and thrombosis
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In patients with Type 1 diabetes, the secretions of both glucagon and epinephrine
are defective in response to hypoglycemia, due to a combination of autonomic
neuropathy and defects associated with recurrent hypoglycemia.6
In patients with severe insulin deficiency, a prolonged fast in the absence of
adequate insulin can lead to excessive glycogenolysis and increased gluconeogenesis
and ketogenesis, resulting in hyperglycemia and ketoacidosis. Similar problems may
ensue in patients with Type 2 diabetes also in response to a prolonged fast; however,
ketoacidosis is uncommon, and the severity of hyperglycemia depends on the extent
of insulin resistance and/or deficiency.6
The transition from a fed state to a fasted state may be divided into three stages:7
1. The postabsorptive phase, 624 hours after beginning fasting
2. The gluconeogenic phase, from 210 days of fasting
3. The protein conservation phase, beyond 10 days of fasting.
Although Ramadan fasts do not exceed 24 hours, the variability of the duration of
every phase may lead to different physiological responses to fasting. This variability
may explain the feasibility of prolonged fast even in subjects with Type 1 diabetes in
some studies.8
The average rate of glucose utilization by a healthy man is about 7 g/hour after an
overnight fast. The liver of a normal person contains about 80 g of glycogen which can
supply glucose to the brain and peripheral tissues for about 12 hours.9
Diabetic patients who fast during Ramadan are prone to develop various
complications, if they have the following risk factors and should avoid fasting since
they are at high risk of complications.
Type 1 diabetes mellitus especially brittle
Ketoacidosis, severe hypoglycemia or hyperosmolar hyperglycemic coma within
the 3 months prior to Ramadan
A history of recurrent hypoglycemia
Hypoglycemia unawareness
Sustained poor glycemic control: Glycated hemoglobin [HbA1C (7.59%)]
Any acute illness
Performing intense physical labor
Pregnancy
Chronic dialysis
The following factors are important for healthy children above 12 years who wish
to fast during Ramadan.
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NUTRITIONAL ADVICE
PHYSICAL ACTIVITY
There is a wrong notion amongst some Muslims that blood tests and administration
of parenteral drugs including insulin are forbidden during Ramadan fasting.
Muslim scholars are of the opinion that blood tests for glucose monitoring and
insulin injection do not invalidate Ramadan fasting.
The importance of frequent home monitoring of glycemic status should be stressed
to patients and their parents.
If blood glucose is more than 270 mg/dL (15 mmol/L), urine should be checked for
ketone bodies.
It should be stressed that all patients should immediately end their fast if
hypoglycemia occurs (blood glucose of 60 mg/dL or 3.3 mmol/L), since there is
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no guarantee that their blood glucose will not drop further if they wait or delay
treatment. The fast should also be broken if blood glucose reaches 70 mg/dL
(3.9 mmol/L) in the first few hours after the start of the fast, especially if insulin,
sulfonylurea drugs or meglitinide are taken at predawn. Finally, the fast should
also be broken if blood glucose exceeds 300 mg/dL (16.7 mmol/L).
Fast should be terminated if child develops clinical features suggestive of
hypoglycemia.
A child who is sick should not be allowed to fast.
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REFERENCES
1. Miller T (Ed). Mapping the Global Muslim Population: A Report on the Size and
Distribution of the Worlds Muslim Population. [online] Washington, DC, Pew Research
Center. Available from http:// pewforum.
org/newassets/images/reports/Muslim
population/Muslim population. [Accessed June, 2013]
2. Salti I, Benard E, Detournay B, et al. The EPIDIAR Study Group: A population-based study
of diabetes and its characteristics during the fasting month of Ramadan in 13 countries:
results of the Epidemiology of Diabetes and Ramadan 1422/2001 (EPIDIAR) study.
Diabetes Care. 2004;27:2306-11.
3. Arouj MA, Khalil SA, Buse J, et al. Recommendations for management of diabetes during
Ramadan. Diabetes Care. 2010;33:1895-1902.
4. Mohamad GA, Car N, Muacevic-Katanec. Fasting of persons with diabetes during
Ramadan. Diabetologia-Croatica. 2002.pp.31-2.
5. Al-Khawari M, Al-Ruwayeh A, Al-Doub K, et al. Adolescents on basal-bolus insulin can
fast during Ramadan. Pediatric Diabetes. 2010;11:96-100.
6. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes (Review). Diabetes Care.
2003;26:1902-12.
7. Felig P. Starvation. In: Endocrinology. De- Groot LJ (Ed). New York: Grune & Stratton;
1979. pp. 1927-40.
8. Reiter J, Wexler ID, Shehadeh N, et al. Type 1 diabetes and prolonged fasting. Diabet Med.
2007;24:436-9.
9. Cahill GF. Starvation in man. N Engl J Med. 1970;282:668-75.
10. Kadiri A, Al-Nakhi A, El-Ghazali S, et al. Treatment of type 1 diabetes with insulin lispro
during Ramadan. Diabetes Metab. 2001;27:482-6.
11. Jaleel MA, Raza SA, Fathima FN, et al. Ramadan and diabetes: As-Saum (The fasting).
Indian J Endocrinol Metab. 2011;15:268-73.
12. Al Arouj M, Bouguerra R, Buse J, et al. Recommendations for management of diabetes
during Ramadan. Diabetes Care. 2005;28:2305-11.
13. Salman H, Abdullah MA, Abanamy MA, et al. Ramadan fasting in diabetic children in
Riyadh. Diabet Med.1992;9:583-4.
14. Bin-Abbas BS, Sakati N, Raef H, et al. Continuous subcutaneous insulin infusion in
type 1 diabetic Saudi children: A comparison with conventional insulin therapy. Saudi
Med J. 2005;26:918-22.
15. Bin-Abbas BS, Sakati N, Al-Ashwal AA. Continuous subcutaneous insulin infusion in type
1 diabetic Saudi children. A comparison with multiple daily insulin injection therapy.
Ann of Saudi Med. 2006;26:327-8.
Chapter
16
Abstract
Ramadan is one of the five main pillars of Islam. Muslims are obliged to abstain from food and drink
from dawn to sunset during the month of Ramadan. Although the sick, menstruating, pregnant and
nursing women may be exempted, many still choose to fast while others are more careful in practicing it. The research to date regarding effects of Ramadan fasting in pregnancy and lactation seems
generally reassuring. However, there is inadequate evidence to conclude fasting during these periods
is completely safe. Many of the existing studies are small or methodologically flawed. Imbedded in
the clinical and medical implications of fasting in these women is a very complex social, religious
and spiritual context that influences the health beliefs and practices of Muslim women, especially
in Ramadan. Doctors and health workers need to understand the religious obligations of a Muslim
towards fasting during Ramadan and strike a balance between the religious and health concerns of
women. Only through this can a healthcare provider adequately counsel Muslim patients and allow
informed decision with regards to fasting.
INTRODUCTION
150
150
than 50 miles, menstruating women, pregnant and nursing women who are worried
about their health and/or pregnancy, and those with learning difficulties or mental
retardation such that they are unable to comprehend the nature and purpose of the
fast.2 This flexibility offered by the religion may not be reflected in the attitudes of
observers of Islam. It has been shown that a significant proportion of those who are ill
and/or on special diets will fast, thereby not taking their medication or stopping their
diets.3
The holy month of Ramadan is an important time for Muslim women, but
healthcare providers taking care of Muslim women face the difficult task of advising
them about the safety of fasting during pregnancy and breastfeeding. Providing this
advice and counsel requires that the healthcare providers understand and respect
beliefs and practices during this time to be able to provide appropriate and sensitive
care. This article discusses health beliefs and practices of Muslim women during
the fasting month of Ramadan as well as provides recommendations to healthcare
providers.4
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Ramadan fasting in the second or third trimester of gestation has been associated
with reduced mean placental weight and a reduced ratio of placental weight to
birthweight. However birthweight does not seem to be affected, which suggests
that the placentas are able to maintain levels of activity despite their reduced size.
Changes in placental growth during Ramadan could be associated with altered fetal
programming, and may therefore have long-term implications for the health of the
next generation.15
Although the research to date is generally reassuring, there is inadequate evidence
to conclude that prenatal fasting is safe. Hence, healthcare givers face the daunting
task of providing accurate and appropriate medical advice to women who wish to fast
during their pregnancies (Table 1). On the one hand, the doctor has to determine the
Diet:
Stop caffeine and cigarettes gradually in
advance
Get up for Suhur (AM meal)
Eat high fiber, whole grains, fruits,
vegetables, nuts
Avoid excess salt, sugar and caffeine
Drink water, milk and juice just before
dawn
Breakfast with water and dates (this is a
tradition)
Balanced, nutritious evening meal and
plenty of fluids
Bedtime snack including water or juice,
protein and fruit
Contd
152
152
Contd
Source: Adapted from Robinson T, Raisler J. Each one is a doctor for herself. Ramadan fasting among Muslim
women in the United States. Ethn Dis. 2005;15(Suppl 1):S1-99-103.
general good health of the mother, the unborn baby, and the pregnancy prior to and
during the fast. In the presence of coexisting medical conditions, the doctor also has to
ensure that the medical condition and medication schedule will not be compromised
by the fast. On the other hand, the doctor has to be sensitive to the patients wish to
fulfill her religious obligation. It is far better that the patient fasts with the knowledge
of her doctor and hence, closer monitoring by her doctor may be instituted than if
she fasts against medical advice and returns to consult the doctor only when the
whole Ramadan is over. Therefore, it is important that the doctor provides a careful
153
153
explanation and counseling which will allow a Muslim woman to make an informed
decision whether to start and/or continue her fast during pregnancy.2
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154
Fasting, especially among patients with Type 1 diabetes with poor glycemic control,
is associated with multiple risks. The major potential risks associated with fasting
in patients with diabetes are hypoglycemia, hyperglycemia, diabetic ketoacidosis
and dehydration and thrombosis. Fasting for patients with diabetes represents an
important personal decision that should be made in light of guidelines for religious
exemptions and after careful consideration of the associated risks following ample
discussion with the treating physician.
In general, women with pregestational or gestational diabetes should be strongly
advised to not fast during Ramadan. However, if they insist on fasting, then special
attention should be given to their care. Pre-Ramadan evaluation of their medical
condition is essential. This includes preconception care with emphasis on achieving
near-normal blood glucose and A1C values, counseling about maternal and fetal
complications associated with poor glycemic control, and education focused on
self-management skills. Ideally, patients should be managed in high-risk clinics.
The management of pregnant patients during Ramadan is based on an appropriate
diet and intensive insulin therapy with more frequent monitoring and insulin dose
adjustment.22
Medication noncompliance has been related to fasting; some Muslims believe
that using oral medications, injections, or inhalers during the fasting hours breaks
their fast. Others believe that using only oral and intravenous medications would
break their fast. Nose drops, creams and ointments, suppositories, and patches are
considered religiously proper to use during the fasting hours. As a result, depending
on type of medication being used during Ramadan, patients may change the way they
take their medication arbitrarily, which could lead to serious medication interaction
and adverse outcomes.4
CONCLUSION
The religion of Islam values life. Although fasting during Ramadan is one of the
obligations of the religion, flexibility exists. Islam has enabled the sick, pregnant and
nursing mothers not to fast during Ramadan, and states that one is permitted not to
fast or to break fast to save a life. Furthermore, those who may harm others by fasting
may stop fasting. Health care providers need to be knowledgeable about religious and
cultural phenomena, conduct research to investigate the effects of Ramadan fasting,
and form links with the teachings of Islam to find religiously and culturally acceptable
methods to combat the possible unfavorable effects for women, infants and children.16
REFERENCES
1. Lamri-Senhadji MY, El Kebir B, Belleville J, et al. Assessment of dietary consumption and
time-course of changes in serum lipids and lipoproteins before, during and after Ramadan
in young Algerian adults. Singapore Med J. 2009;50 (3):288-94.
2. Josooph J, Abu J, Yu SL. A survey of fasting during pregnancy. Singapore Med J.
2004;45(12):583-6.
3. Ertem IO, Kaynak G, Kaynak C, et al. Attitudes and practices of breastfeeding mothers
regarding fasting in Ramadan. Child Care, Health and Dev. 2001;27:545-54.
155
155
4. Kridli SA. Health beliefs and practices of Muslim women during Ramadan. MCN: Am J
Matern Child Nurs. 2011;36:216-21.
5. Cross JH, Eminson J, Wharton BA. Ramadan and birth weight at full term in Asian Moslem
pregnant women in Birmingham. Arch Dis Child. 1990;65:1053-6.
6. Ozturk E, Balat O, Ugur MG, et al. Effect of Ramadan fasting on maternal oxidative stress
during the second trimester: A preliminary study. J Obstet Gynaecol. 2011;37:729-33.
7. Moradi M. The effect of Ramadan fasting on fetal growth and Doppler indices of pregnancy.
J Res Med Sci. 2011;16:165-9.
8. Kavehmanesh Z, Abolghasemi H. Maternal fasting and neonatal health. J Perinatol.
2004;24:748-50.
9. Arab M, Nasrollahi S. Interrelation of Ramadan fasting and birth weight. Medical Journal
of Islamic Academy of Sciences. 2001;14:91-5.
10. Robinson T, Raisler J. Each one is a doctor for herself. Ramadan fasting among Muslim
women in the United States. Ethn Dis. 2005;15(Suppl 1):S1-99-103.
11. Opaneye AA, Villegas DD, Azeim AA. Islamic festivals and low birth weight infants. J R Soc
Health. 1990;110:106-7.
12. Sulimani R, Anani M, Khatib O, et al. Should diabetic pregnant mothers fast during
Ramadan? Saudi Med J. 1997;19(1):50-1.
13. Malhotra A, Scott PH, Scott J, et al. Metabolic changes in Asian Muslim pregnant mothers
observing the Ramadan fast. Br J Nutr. 1989;61:663-72.
14. Leiper JB, Molla AM, Molla AM. Effects on health of fluid restriction during fasting in
Ramadan. Eur J Clin Nutr. 2003;57:S30-8.
15. Alwasel SH, Abotalib Z, Aljarallah JS, et al. Changes in Placental Size during Ramadan.
Placenta. 2010;31:607-10.
16. Ertem IO, Kaynak G, Kaynak C, et al. Attitudes and practices of breastfeeding mothers
regarding fasting in Ramadan. Child Care Health Dev. 2001;27:545-54.
17. Perez-Escamilla R. Breastfeeding in Africa and the Latin American and Caribbean Region:
the potential for urbanization. J Trop Paediatr. 1994;40:137-43.
18. Prentice AM, Lamb WH, Prentice A, et al. The effect of water abstention on milk synthesis
in lactating women. Clin Sci. 1984;66:291-8.
19. Bener A, Galadari S, Gillet M, et al. Fasting during the holy month of Ramadan does not
change the composition of breast milk. Nutr Res. 2001;21:859-64.
20. Khoshdel A, Najafi M, Kheiri S, et al. Impact of Maternal Ramadan Fasting on Growth
Parameters in Exclusively Breast-fed Infants. Iran J Pediatr. 2007;17:345-52.
21. Salti I, Bnard E, Detournay B, et al. Results of the Epidemiology of Diabetes and Ramadan
14222001 (EPIDIAR) study. Diabetes Care. 2004;27:2306-11.
22. Al-Arouj M, Bouguerra R, Buse R, et al. Recommendations for management of diabetes
during Ramadan. Diabetes Care. 2005;28:2305-11.
Chapter
17
Abstract
The holy month of Ramadan is one of the five pillars of being a Muslim. Although the Quran exempts
sick people, the elderly and the travelers from the duty of fasting, many Muslims with diabetes may
not perceive themselves as sick and are keen to fast. Further, the elderly patients often have multiple
co-morbid conditions putting them at increased risk of hypoglycemia, hyperglycemia, dehydration
and thrombosis. No specific recommendations for the management of diabetes in elderly individuals
have been published because of lack of clinical trials. The incretin mimetics are potentially safer
during Ramadan and provide effective and safe therapeutic options, administered either alone or
in combination with metformin or sulfonylurea. Among the sulfonylurea, gliclazide MR (modified
release) and glimepiride can be safely used during Ramadan, but glibenclamide should be avoided
particularly in elderly due to the associated risk of hypoglycemia. In selected patients with Type 2
diabetes mellitus (T2DM), the long-acting insulin analogs glargine and detemir, as well as the premixed insulin analogs, can be used with minimal risk of metabolic derangement or hypoglycemia.
Pre-Ramadan assessment, counseling, meal planning, frequent glucose monitoring, appropriate
physical activity, dosages and time of medication should be provided at least 3060 days before
Ramadan to the elderly patients who insist on fasting. Further, clinical trials are needed to evaluate
the safety and efficacy of new antidiabetic agents and new diabetes-related technologies in elderly
patients during Ramadan.
INTRODUCTION
157
157
and Ramadan (EPIDIAR) Study conducted in 13 Islamic countries showed that about
43 percent and 79 percent respectively of Muslims with Type 1 and Type 2 diabetes
fast during Ramadan meaning that more than 50 million individuals with diabetes
fast during Ramadan.2
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158
management have been described among some health care professionals.5 Special
classes may need to consider enhancing self-management during this month.6 Expert
doctors should take the time to give interviews preferably jointly with Imams to offer
clear and authoritative views and respond to all commonly asked questions. In the
clinical settings, doctors should have a clear understanding of the religious ruling on
fasting to give their advice with confidence.
Education Counseling
Each individual needs to be counseled about the essential elements necessary to
render fasting safer. These include the importance of glucose monitoring during fasting
and nonfasting hours, when to stop the fast, meal planning to avoid hypoglycemia
and dehydration during prolonged fasting hours, and the appropriate meal choice to
avoid postprandial hyperglycemia. The educational program should include advice
on the timing and intensity of physical activity during fasting as well.
Diet-controlled Patients
The risk associated with fasting is low. However, there is still a potential risk for
occurrence of postprandial hyperglycemia after the predawn and sunset meals in
patients over-indulge in eating. Distribution of calories over two to three smaller
meals during the nonfasting interval may help prevent excessive postprandial
hyperglycemia.
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159
160
160
Incretin-based Therapy
Gliptins or dipeptidyl peptidase-IV (DPP IV) inhibitors are new oral hypoglycemic
agents which act as selective inhibitors of enzyme DPP-IV to enhance endogenous
incretin activity by preventing the rapid degradation of the incretin hormones,
glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide
(GIP). These classes of agents are not independently associated with hypoglycemia,
though they can increase the hypoglycemic effects of sulfonylurea, glinides and
insulin. Gliptins are important addition to the currently available management
options for patients with Type 2 diabetes and are among the best tolerated drugs
for the treatment of T2DM. They can cause modest A1C reduction and are weight
neutral. Many consider DPP-IV as a substitute to sulfonylurea. DPP-IV Is among the
best tolerated drugs for the treatment of drugs and importantly vis-a-vis treatment
during Ramadan, do not require titration. However, there are no specific studies of
these agents during periods of fasting in Ramadan among elderly patients available.
Alpha-Glucosidase Inhibitors
This group of antidiabetic agents inhibits the action of intestinal brush border
enzyme, -glucosidase, and retards the absorption of carbohydrate when taken with
meal. Because they are not associated with an independent risk of hypoglycemia,
particularly in the fasting state, they may be particularly useful during Ramadan.
As a group, these drugs are only moderately effective and do not exert much effect
on fasting glucose levels and hence are mostly used in combinations with other
anti-diabetic agents. -glucosidase inhibitors are associated with frequent mild to
moderate gastrointestinal effects, particularly flatulence however, no studies of these
agents during period of fasting in Ramadan among elderly patients are available.
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hyperglycemia. An effective strategy would be judicious use of intermediate or longacting insulin preparations plus short-acting insulin administered before meals.
Although hypoglycemia tends to be less frequent, it is still a risk especially in patients
who have required insulin therapy for a number of years or in whom insulin deficiency
predominates in the pathophysiology. Very elderly patients with Type 2 diabetes may
be at high-risk.
Insulin can be safely used in Type 2 diabetic individuals twice daily premixed
insulin such as lispro mix (25/75) and human insulin (30/70) have been used safely
during Ramadan.14 It is recommended that the usual morning dose of this regimen be
used with the sunset meal and half the usual evening dose be used with the predawn
meal.15 Insulin Glargine is also effective and safe during Ramadan and can be given as
single injection at 10 pm with or without mealtime short-acting analogs or other oral
antidiabetic medications.16
CONCLUSION
Fasting during Ramadan for patients with diabetes, particularly elderly, individuals
carries a risk of an assortment of complications. Elderly patients with Type 2 diabetes
additionally will have multiple comorbid conditions that put them at increased risk
of hypoglycemia, dehydration and other diabetes related complications. In general,
patients with Type 1 diabetes are at very high-risk of life-threatening complications.
Hypo- and hyperglycemia may also occur with Type 2 diabetes, but is generally less
frequent and has less severe consequences. Patients who insist on fasting should
undergo Pre-Ramadan assessment and receive appropriate education, counseling
and instructions related to physical activity, meal planning, glucose monitoring, and
dosage and timing of medication.
Newer pharmacological agents have lesser hypoglycemic potential and may have
specific advantages during Ramadan, but in general these challenging therapeutic
situations have not been adequately addressed in clinical trials particularly elderly
patients of T2DM who insist on fasting.
REFERENCES
1. Miller T, Edi. Mapping the global Muslims populations: A case report on the size
and distribution of the Worlds Populations [online] C2009-Washington, DC, Peu
Research Centre. Available from http//peuforum.org/newassests/images/reports/
muslimspopulations /pdf. [Assessed October, 2009].
2. Salti I, Benard E, Detournay B, et al. EPIDIAR study group. A population based study of
diabetes and its characteristics during the fasting monthe of Ramadan in 13 countries:
Results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study.
Diabetes Care. 2004;27:2306-11.
3. The Holy Quran. Sura 2: verses 183-5.
4. Al-Amouli A, Al-Ulagi N, Bashir M, et al. Education for diabetic patients for fasting of
Ramadan a questionnare study. Endocrine Abstract. 2006;11:277.
5. Barrow L. Ramadan and diabetes: helping to ensure safe fasting. J Diabetes Nursing.
2004;8(6):277-323.
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Section
5
Management of
Complications
CHAPTERS
18.
Hypoglycemic Emergencies
19.
20.
Dyselectrolytemia in Ramadan
21.
Chapter
18
Hypoglycemic Emergencies
Intekhab Ahmed
Abstract
Hypoglycemia is potentially a life-threatening complication of diabetes management. In a diabetic
person, it is commonly the result of inadvertent over treatment of hyperglycemia or due to mismatch
between diabetic medication and food intake, lack of food intake, or excessive physical exertion
in the absence of adequate medication adjustment. Patients especially elderly are more prone to
hypoglycemia during the month of Ramadan if no appropriate adjustment is made in their diabetic
medications.
In this chapter, a brief description of definition of hypoglycemia, its symptoms and signs, predisposing factors, and measures how to prevent hypoglycemia and its management is discussed.
A thorough understanding of the diabetic disease process, its medications and their side effects
especially secretagogues and insulin, and a close interaction between patient and physician is of
paramount importance to avoid hypoglycemia.
INTRODUCTION
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CLINICAL MANIFESTATIONS
Symptoms
The symptoms of hypoglycemia in patients with diabetes are nonspecific.
Hypoglycemia causes neurogenic (autonomic) and neuroglycopenic symptoms.
The neurogenic symptoms: It includes tremor, palpitations, and anxiety/arousal
(catecholamine-mediated, adrenergic) and sweating, hunger, and paresthesias
(acetylcholine-mediated, cholinergic). They are largely caused by sympathetic
neural, rather than adrenomedullary, activation.4-5
The neuroglycopenic symptoms: It includes cognitive impairment, behavioral
changes, psychomotor abnormalities and, at lower plasma glucose concentrations,
seizure and coma. Although profound prolonged hypoglycemia can cause brain
death in the unobserved patient with diabetes, the vast majority of episodes are
reversed after the glucose level is raised to normal and the rare fatal episodes are
generally thought to be the result of ventricular arrhythmia.5-6
It is important to remember that not all the patients experience symptoms of
hypoglycemia and the patient may not recognize the symptoms, even though they are
evident to an observer.7 Furthermore, many patients cannot describe their episodes
in any detail because of amnesia, so that information should be obtained from a close
family member or friend whenever possible.
The symptoms may also be absent because of hypoglycemia unawareness, which
is thought to be the result of reduced sympathoadrenal, predominantly sympathetic
neural, responses to a given degree of hypoglycemia caused by recent antecedent
hypoglycemia, prior exercise or sleep in patients with diabetes.
Signs
Diaphoresis and pallor are common signs of hypoglycemia. Heart rate and systolic
blood pressure are raised, but not greatly. Neuroglycopenic manifestations are
often observable. Occasionally, transient neurological deficits occur. Permanent
neurological damage is rare and, should it occur, it would be more likely in a patient
with diabetes and prolonged severe hypoglycemia.8
Clinical Classification
The ADA workgroup on hypoglycemia recommends the following classification of
hypoglycemia in diabetes:9
Severe hypoglycemia: An event requiring the assistance of another person to
actively administer carbohydrate/glucagon or other resuscitative actions is
classified as a severe hypoglycemic event. Plasma glucose measurements may
not be available during such an event, but neurological recovery attributable to
restoration of plasma glucose to normal is considered sufficient evidence that the
event was induced by a low plasma glucose concentration.
Documented symptomatic hypoglycemia: An event during which typical symptoms
of hypoglycemia are accompanied by a measured (typically with a monitor
or with a validated glucose sensor) plasma glucose concentration less than
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Type 1 Diabetes
Hypoglycemia occurs frequently in patients with Type 1 diabetes. The average patient
suffers up to two episodes of symptomatic hypoglycemia per week, and one episode
of temporarily disabling hypoglycemia per year.10 Severe hypoglycemia events, the
most reliable values albeit representing only a small fraction of the total hypoglycemic
experience, have been reported to range from 62170 episodes per 100 patient years
in Type 1 diabetes. In the Diabetes Control and Complications Trial (DCCT), a greater
proportion of patients in the intensively treated group had at least one episode of
severe hypoglycemia (65 vs 35% of patients in the control group), with overall rates of
61 and 19 per 100 patient-years, respectively.11
Type 2 Diabetes
Hypoglycemia is less common in Type 2 diabetes. However, because there are a
greater number of individuals with Type 2 than Type 1 diabetes, and because most
people with Type 2 diabetes ultimately require treatment with insulin, most episodes
of iatrogenic hypoglycemia occur in people with Type 2 diabetes.
Among the commonly used insulin secretagogues (sulfonylureas, meglitinides),
hypoglycemia is most often reported in patients taking long-acting drugs, such as
glyburide (glibenclamide).12
Hypoglycemia is relatively uncommon during treatment with insulin early
in the course of Type 2 diabetes. However, its frequency increases, approaching
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Type 1 diabetes, as patients approach the insulin deficient end of the spectrum of
Type 2 diabetes. In contrast to insulin and insulin secretagogues, agents that do not
cause unregulated hyperinsulinemia, such as metformin, alpha glucosidase inhibitors
(acarbose, miglitol, voglibose), TZDs (pioglitazone, rosiglitazone), glucagonlike peptide-1(GLP-1) receptor agonists (exenatide, liraglutide), and dipeptidyl
peptidase-4 (DPP-4) inhibitors (sitagliptin, saxagliptin, vildagliptin) probably do not
cause hypoglycemia. However, they increase the risk if used with insulin or an insulin
secretagogue.13
Nocturnal Hypoglycemia
A particular problem is nocturnal hypoglycemia, which can lead to disruption of
sleep and delays in correction of the hypoglycemia. Night-time is typically the longest
period between self-monitoring of plasma glucose, between food ingestion, and the
time of maximum sensitivity to insulin. Nocturnal hypoglycemia is less common in
individuals using rapid acting insulin analogs (lispro, aspart, glulisine) rather than
regular insulin before meals and in individuals using long-acting insulin analogs
(glargine, detemir) rather than NPH as the basal insulin.
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Insulin Excess
Absolute or relative insulin excess occurs in the following settings:
Insulin (or insulin secretagogue) doses are excessive, ill-timed or of the wrong type
Exogenous glucose influx is reduced (e.g. during an overnight fast or following
missed meals)
Insulin-independent glucose utilization is increased (e.g. during and shortly after
exercise)
Sensitivity to insulin is increased (e.g. hours after exercise, in the middle of the
night, following improved glycemic control or weight loss)
Endogenous glucose production is reduced (e.g. following alcohol ingestion)
Insulin clearance is reduced (e.g. with renal failure).
Elderly Patients
The risk of hypoglycemia is related to the duration of diabetes and appears to be
increased in the elderly. Older adults may have more neuroglycopenic manifestations
of hypoglycemia (dizziness, weakness, delirium, confusion) compared with adrenergic
manifestations (tremors, sweating).1-4,15
Severe hypoglycemia has been associated with an increased risk of dementia,
even mild episodes of hypoglycemia may result in adverse outcomes in frail elderly;
episodes of dizziness or weakness increase the risk of falls and fracture.
Other Risks
Although insulin secretagogues and insulin are the most common drugs associated
with hypoglycemia, other drugs that are often prescribed for people with diabetes and
that possibly increase the risk of hypoglycemia are angiotensin-converting enzyme
(ACE) inhibitors, angiotensin II antagonists, and nonselective beta-2-adrenergic
antagonists.16
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Glycemic Targets
Target A1C levels in patients with Type 1 and 2 diabetes should be tailored to the
individual, balancing the improvement in microvascular complications with the risk
of hypoglycemia. Less stringent treatment goals may be appropriate for the month of
Ramadan and in patients with a history of severe hypoglycemia, patients with limited
life expectancies, very young children or older adults, and individuals with comorbid
conditions.
Insulin Regimens
In patients with Type 1 or Type 2 diabetes who use insulin, the use of long-acting
insulin analogs (e.g. glargine, detemir) as the basal insulin can be replaced with
NPH twice a day and rapid-acting insulin analogs (e.g. lispro, aspart, glulisine) as
the pre-meal bolus insulin at Sehar and Iftar can reduce the risk of hypoglycemia,
particularly nocturnal hypoglycemia. Patients on insulin pump should adjust their
basal rate to keep their blood sugar between 100 mg dL and 140 mg/dL.14-17
Oral Hypoglycemics
All the long acting sulfonylureas (glipizide, gluburide) should be avoided during the
fasting month and be replaced with either prandin or DPP 4 inhibitors. Metformin
and TZDs use is not known to cause hypoglycemia and are safe choice during the
month of Ramadan, provided no contraindications exists.
Other Medications
It is important that patient and physicians are aware of all the medications that can
mask the symptoms or signs of hypoglycemia (beta blockers) and others that can
precipitate hypoglycemia like ACE-inhibitors.
Strong advice about avoidance of strenuous exercise or activity during fasting is a
necessity to prevent hypoglycemia.
Behavioral Approaches
Avoidance of severe hypoglycemia requires the recognition of early symptoms and
signs by the patient (and by those around them). Using a variety of well-validated
behavioral approaches, people can be trained to improve their ability to recognize
hypoglycemia. Furthermore, this increase in recognition may be associated with
long-term improvement in A1C values and a reduction in the number of severe
hypoglycemic events. Blood glucose awareness training involves techniques in which
patients are asked to guess their blood glucose concentration, record their symptoms,
and then verify the blood glucose values with a glucose meter.17-20
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Hypoglycemia Unawareness
If there is a history of hypoglycemia unawareness, a 23 weeks period of avoidance
of hypoglycemia is advisable since that often restores awareness.21-22 That can be
accomplished by more intensive professional involvement (e.g. by telephone); in
practice, it may require higher glycemic goals for the month of Ramadan.
TREATMENT OF HYPOGLYCEMIA
Asymptomatic
When SMBG reveals a blood glucose of less than or equal to 70 mg/dL (3.9 mmol/L),
it is reasonable for a person with drug-treated diabetes to consider defensive actions.
The options include repeating the measurement in the near term, avoiding critical
tasks such as driving, ingesting carbohydrates, and adjusting the treatment regimen.23
Symptomatic
In order to treat early symptoms of hypoglycemia, patients should be certain that fastacting carbohydrate (such as glucose tablets, hard candy, or sweetened fruit juice) is
available at all times. Fifteen to twenty grams is usually sufficient to raise the blood
glucose into a safe range without inducing hyperglycemia. This can be followed by
long-acting carbohydrate to prevent recurrent symptoms.
In patients taking insulin or an insulin secretagogue in combination with an alphaglucosidase inhibitor (acarbose, miglitol, voglibose), only pure glucose (dextrose)
should be used to treat symptomatic hypoglycemia.24 Other forms of carbohydrates,
such as table sugar (sucrose), will be less effective in raising blood sugar as alphaglucosidase inhibitors slow digestion of other carbohydrates.
Severe
When the patient is unconscious or unable to ingest carbohydrate, it is necessary that
close friends or relatives be trained to recognize and treat this complication. Dealing
with a loved one who is pale, sweaty, acting in a bizarre fashion, or unconscious and
convulsing is often a terrifying situation, yet one that can be reversed with an injection
of glucagon. Successful glucagon therapy requires that the glucagon kit can be located
and that the relative or friend is able to remain calm, and able to inject prefilled
glucagon injection. The glucagon kit should be checked regularly and replaced when
it is beyond its expiration date.
A subcutaneous or intramuscular injection of 0.51.0 mg of glucagon will usually
lead to recovery of consciousness within 1015 minutes, although it may be
followed by marked nausea or even vomiting.25
Patients brought to the hospital can be treated more quickly by giving 25 g of
50 percent glucose (dextrose) intravenously. A subsequent glucose infusion (or
food, if patient is able to eat) is often needed, depending upon the cause of the
hypoglycemia.26
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CONCLUSION
Hypoglycemia in a diabetic person, if unrecognized can be a frightening and fatal
event. Most common cause of hypoglycemia in diabetics is a mismatch in insulin
and food intake, which is especially common in the setting of fasting. A complete
understanding of the diabetes, risk factors for hypoglycemia, its recognition are of
utmost importance for the patient in general and particularly in a diabetic patient
who is planning to observe the month of Ramadan with full religious vigor. A close
communication between patient and physician, frequent evaluation of blood sugar
readings, and timely adjustments in medications are the corner stone of preventing
hypoglycemia. A mild hyperglycemia in the month of Ramadan is much better than
any episode of hypoglycemia.
REFERENCES
1. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes
Association Workgroup on Hypoglycemia, American Diabetes Association. Diabetes Care.
2005;28(5):1245-9.
2. Cryer PE. Hypoglycemia in Diabetes. Pathophysiology, Prevalence and Prevention.
American Diabetes Association, Alexandria, VA, 2009.
3. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol
Metab. 2009;94(3):709-28.
4. Hepburn DA, Deary IJ, Frier BM, et al. Symptoms of acute insulin-induced hypoglycemia
in humans with and without IDDM. Factor-analysis approach. Diabetes Care.
1991;14(11):949-57.
5. DeRosa MA, Cryer PE. Hypoglycemia and the sympathoadrenal system: neurogenic
symptoms are largely the result of sympathetic neural, rather than adrenomedullary,
activation. Am J Physiol Endocrinol Metab. 2004;287(1):E32-41.
6. Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest.
2007;117(4):868-70.
7. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and Diabetes: A Report of a
Workgroup of the American Diabetes Association and the Endocrine Society. Diabetes
Care. 2013;36:1384-95.
8. Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008;57:3169-76.
9. Cryer PE, Axelrod L, Grossman AB, et al. Endocrine Society. Evaluation and management
of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin
Endocrinol Metab. 2009;94:709-28.
10. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects
of treatment modalities and their duration. Diabetologia. 2007;50(6):1140-7.
11. Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and
Complications Trial Research Group. Diabetes. 1997;46(2):271-86.
12. Donnelly LA, Morris AD, Frier BM, et al. Collaboratio Frequency and predictors of
hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study.
Diabet Med. 2005;22(6):749-55.
13. Holstein A, Plaschke A, Egberts EH. Clinical characterisation of severe hypoglycaemiaa
prospective population-based study. Exp Clin Endocrinol Diabetes. 2003;111(6):364-9.
14. Ertl AC, Davis SN. Evidence for a vicious cycle of exercise and hypoglycemia in type 1
diabetes mellitus. Diabetes Metab Res Rev. 2004;20(2):124-30.
173
173
15. Gangji AS, Cukierman T, Gerstein HC, et al. A systematic review and meta-analysis
of hypoglycemia and cardiovascular events: a comparison of glyburide with other
secretagogues and with insulin. Diabetes Care. 2007;30(2):389-94.
16. Phung OJ, Scholle JM, Talwar M, et al. Effect of noninsulin antidiabetic drugs added to
metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes.
JAMA. 2010;303(14):1410-8.
17. Murad MH, Coto-Yglesias F, Wang AT, et al. Clinical review: Drug-induced hypoglycemia:
a systematic review. J Clin Endocrinol Metab. 2009;94(3):741-5.
18. Cox DJ, Gonder-Frederick L, Ritterband L, et al. Prediction of severe hypoglycemia.
Diabetes Care. 2007;30(6):1370-3.
19. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care. 2003;26(6):190212.
20. Pogach L, Aron D. Balancing hypoglycemia and glycemic control: a public health approach
for insulin safety. JAMA. 2010;303(20):2076-7.
21. Cryer PE. Elimination of hypoglycemia from the lives of people affected by diabetes.
Diabetes. 2011;60(1):24-7.
22. Yudkin JS, Richter B, Gale EA. Intensified glucose lowering in type 2 diabetes: time for a
reappraisal. Diabetologia. 2010;53(10):2079-85.
23. Cox DJ, Kovatchev B, Dachev S, et al. Hypoglycemia anticipation, awareness and treatment
training (HAATT) reduces occurrence of severe hypoglycemia among adults with type 1
diabetes mellitus. Int J Behav Med. 2004;11(4): 212-8.
24. Cox DJ, Gonder-Frederick L, Antoun B, et al. Perceived symptoms in the recognition of
hypoglycemia. Diabetes Care. 1993;16(2):519-27.
25. Shipp JC, Delcher HK, Munroe JF. Treatment of Insulin Hypoglycemia in Diabetic
Campers: A Comparison of Glucagon (1 and 2 mg) and Glucose. Diabetes November/
December 1964;13:645-8.
26. Barennes H, Valea I, Nagot N, et al. Sublingual sugar administration as an alternative
to intravenous dextrose administration to correct hypoglycemia among children in the
tropics. Pediatrics. 2005;116(5):e648-53.
Chapter
19
Hyperglycemic
Emergencies in Ramadan
Intekhab Ahmed
Abstract
The two most acute and serious hyperglycemic emergencies are diabetic ketoacidosis (DKA),
and hyperglycemic hyperosmolar, nonketotic state (HHNK). They are part of the spectrum of
hyperglycemia and each represents an extreme in the spectrum. DKA can affect both Type 1 and
Type 2 diabetics while HHNK is limited to Type 2 diabetics. Diabetic patients who observe Ramadan
have to be extremely careful about their diabetic treatment and hydration status (water intake)
especially when Ramadan falls in summer months to avoid these hyperglycemic events especially
elderly Type 2 diabetics as the mortality is up to 520 percent with HHNK.
In this chapter, a brief review of etiology, pathophysiology, treatment and steps to avoid DKA
and HHNK in general and especially in the month of Ramadan are discussed.
INTRODUCTION
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DKA
Mild
Plasma glucose (mg/dL)
Arterial pH
Serum bicarbonate
Urine ketones
Moderate
Severe
> 250
> 250
> 250
600
7.257.30
7.07.24
< 7.00
> 7.30
1518
1015
< 10
> 18
Positive
Positive
Positive
Small
Serum ketones
Positive
Positive
Positive
Small
Serum osmolality
Variable
Variable
Variable
> 320
Anion gap
> 10
> 12
> 12
Variable
Mental status
Alert
Alert/drowsy
Stupor/coma
Stupor/coma
osmolality may reach 380 mosmol/kg and neurologic abnormalities are frequently
present especially comatose state. Most patients with HHNK have an admission
pH greater than 7.30, a serum bicarbonate greater than 20 mEq/L, a serum glucose
greater than 600 mg/dL (33.3 mmol/L), and test negative for ketones in serum and
urine, although mild ketonemia may be present.
There is significant overlap between DKA and HHS has been reported in more
than one-third of patients.4,5 The typical total body deficits of water and electrolytes in
DKA and HHS are compared in a table (Table 2).6
Diabetic ketoacidosis is more common in young (< 65 years) diabetic patients and
in women compared to men.7 Mortality in DKA is primarily due to the underlying
precipitating illness and only rarely to the metabolic complications of hyperglycemia
or ketoacidosis. The prognosis of DKA is substantially worse at the extremes of age
and in the presence of coma and hypotension.8,9 HHNK is the most commonly seen in
individuals older than 65 years with Type 2 diabetes.10 Mortality attributed to HHNK is
higher than that of DKA, with rates ranging from 5 to 20 percent; as in DKA, mortality
is most often due to the underlying illness or comorbidity.
PATHOGENESIS
Two hormonal abnormalities are largely responsible for the development of
hyperglycemia and ketoacidosis in patients with uncontrolled diabetes:11
1. Insulin deficiency and/or resistance.
2. Glucagon excess, which may result from removal of the normal suppressive effect
of insulin.12,13 There is no evidence for defective pancreatic alpha cell function in
diabetes, since there is a normal glucagon response to nonhypoglycemic stimuli.14
Although glucagon excess contributes to the development of DKA, it is not
required. As an example, patients with complete pancreatectomies and who have no
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Table 2: Typical total body deficits of water and electrolytes in diabetic ketoacidosis and
hyperosmolar hyperglycemic state6
DKA
HHNK
Water (mL/kg)
100
100200
Na+ (mEq/kg)
710
513
Cl
(mEq/kg)
35
515
K+
(mEq/L)
35
46
PO4 (mmol/kg)
57
37
Mg+
12
12
(mEq/kg)
pancreatic glucagon will develop DKA if insulin is withheld; however, it takes longer
for DKA to develop compared with patients with Type 1 diabetes. In addition to these
primary factors, increased secretion of catecholamines and cortisol can contribute to
the increases in glucose and ketoacid production.
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Hyperglycemia
Hormonal alterations in DKA and HHNK result in hyperglycemia by their impact on
three fundamental processes in glucose metabolism:18
Impaired glucose utilization in peripheral tissues
Increased gluconeogenesis (both hepatic and renal)
Increased glycogenolysis.
Insulin deficiency and/or resistance in diabetic patients impair peripheral glucose
utilization in skeletal muscle. However, decreased glucose utilization alone will
produce only postprandial hyperglycemia; increased gluconeogenesis is required for
the often severe fasting hyperglycemia seen in DKA and HHNK.
Insulin deficiency and/or resistance promote hepatic gluconeogenesis by two
mechanisms: increased delivery of gluconeogenetic precursors (glycerol and alanine)
to the liver due to increased fat and muscle breakdown;19 and increased secretion of
glucagon by removal of the inhibitory effect of insulin on glucagon secretion and the
glucagon gene.20
The glucosuria associated with DKA and HHNK initially minimizes the rise in
serum glucose. However, the osmotic diuresis caused by glucosuria leads to volume
depletion and a reduction in glomerular filtration rate that limits further glucose
excretion. This effect is more pronounced in HHNK which, as noted above, is usually
associated with a higher serum glucose than seen in DKA.
Ketoacidosis
Both insulin deficiency and glucagon excess contribute to the genesis of DKA.21,22 As
noted above, however, glucagon is not required for DKA to occur.
Acetoacetic acid is the initial ketone formed; it may then be reduced to betahydroxybutyric acid, which is also an organic acid, or nonenzymatically decarboxylated
to acetone, which is chemically neutral.2 Ketones provide an alternate source of energy
when glucose utilization is impaired.
Insulin deficiency and increased catecholamine lead to enhanced lipolysis,
thereby increasing free fatty acid delivery to the liver. Normal subjects will convert
these free fatty acids primarily into triglycerides. The development of ketoacidosis
requires a specific alteration in hepatic metabolism so that free fatty acyl CoA can
enter the mitochondria, where conversion to ketones occurs.22,23
Mitochondrial entry is regulated by the cytosolic enzyme carnitine
palmitoyltransferase I (CPT I), the activity of which varies inversely with malonyl CoA.
Glucagon decreases the production of malonyl CoA, thereby increasing CPT I activity
and ketogenesis. A concurrent increase in hepatic carnitine content contributes to
this process. Insulin does not appear to directly affect hepatic ketogenesis.24
In states of insulin deficiency, the combination of increased free fatty acid delivery
and glucagon excess promotes ketogenesis.
The factors responsible for the general absence of ketoacidosis in HHNK are
incompletely understood. One important factor may be the differential sensitivity of
fat and glucose to the effects of insulin. Studies in humans have demonstrated that
the concentration of insulin required to suppress lipolysis is only one-tenth that
required to promoting glucose utilization. Thus, moderate insulin deficiency, as seen
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in HHNK, might be associated with sufficient insulin to block lipolysis (and therefore
ketoacid formation) but not enough to promote glucose utilization and prevent the
development of hyperglycemia. More severe insulin deficiency will also be associated
with ketoacidosis.25
Precipitating Factors
Multiple factors can precipitate onset and progression of DKA and HHNK. The most
common cause of DKA in Type 1 diabetics is lack of or insufficient insulin action while
the most common cause of HHNK is compromised water intake due to underlying
medical conditions in the elderly. Most of the times, more than one factor contributes
to the onset of these emergencies.
Lack of insulin: Insufficient amount of insulin or its lack especially in Type 1 diabetic
will initiate the cascade resulting in hyperglycemia and ketosis in diabetics.
Infection: Most commonly urinary tract infection or pneumonia can precipitate
DKA and HHNK.
Infarction/Ischemia: Ischemia or any infarction of any organ (heart, brain,
intestine, etc.) will cause a stress on the body in the form of an inflammatory state
and can precipitate DKA or HHNK.
Medications: Drugs that affect carbohydrate metabolism, including glucocorticoids,
higher dose thiazide diuretics, sympathomimetic agents (e.g. dobutamine and
terbutaline),26 and second-generation antipsychotic agents.27 Use of cocaine has
been associated with recurrent DKA.
Psychological problems associated with eating disorders and purposeful insulin
omission, particularly in young patients with Type 1 diabetes.28 Factors that may
lead to insulin omission in younger patients include fear of weight gain, fear of
hypoglycemia, and the stress of chronic disease.
CLINICAL PRESENTATION
Diabetic ketoacidosis usually evolves rapidly, over a 24-hour period while symptoms
of HHNK develop more insidiously with polyuria, polydipsia, and weight loss, often
persisting for several days before hospital admission.
The earliest symptoms of marked hyperglycemia are polyuria, polydipsia, and
weight loss. As the degree or duration of hyperglycemia progresses, neurologic
symptoms, including lethargy, focal signs, and obtundation, which can progress to
coma in later stages, can be seen. Neurological symptoms are the most common in
HHS, while hyperventilation and abdominal pain are primarily limited to patients
with DKA.
Initial Evaluation
Both DKA and HHNK are medical emergencies that require prompt recognition and
management. An initial history and rapid but careful physical examination should
focus on:
Airway, breathing and circulation (ABC) status
Mental status
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by the metabolic acidosis and associated electrolyte abnormalities. Other causes for
abdominal pain should be sought when it occurs in the absence of severe metabolic
acidosis and when it persists after the resolution of ketoacidosis.30
Physical Examination
Signs of volume depletion are common in both DKA and HHNK, including decreased
skin turgor, dry axillae and oral mucosa, low jugular venous pressure and, if severe,
hypotension. Neurologic findings, noted above, also may be seen, particularly in
patients with HHS. Patients with DKA may have a fruity odor (due to exhaled acetone
and similar to the odor of nail polish remover), and deep respirations reflecting the
compensatory hyperventilation (called Kussmaul respirations).
Fever is rare even in the presence of infection, because of peripheral
vasoconstriction due to hypovolemia.
LABORATORY FINDINGS
Hyperglycemia and hyperosmolality are the two primary laboratory findings in
patients with DKA or HHNK; patients with DKA also have a high anion gap metabolic
acidosis. Most patients also have acute elevations in the blood urea nitrogen (BUN)
and serum creatinine concentration, which reflect the reduction in glomerular
filtration rate induced by hypovolemia.
The initial laboratory evaluation of a patient with suspected DKA or HHNK should
include determination of:
Serum glucose
Serum electrolytes (with calculation of the anion gap), BUN and serum creatinine
Complete blood count with differential
Urinalysis, and urine ketones by dipstick
Plasma osmolality
Serum ketones (if urine ketones are present)
Arterial blood gas (if urine ketones or anion gap are present)
Electrocardiogram
Additional testing, such as cultures of urine, sputum, and blood, serum lipase and
amylase, and chest X-ray, should be performed on a case-by-case basis.
Measurement of A1C may be useful in determining whether the acute episode
is the culmination of an evolutionary process in previously undiagnosed or poorly
controlled diabetes or a truly acute episode in an otherwise well-controlled patient.
Serum Ketones
Three ketone bodies are produced in DKA: acetoacetic acid, which is the only true
ketoacid; beta-hydroxybutyric acid, a hydroxyacid formed from the reduction of
acetoacetic acid; and acetone, which is derived from the decarboxylation of acetic
acid. Acetone is a true ketone but is chemically neutral and therefore not an acid.
Urine ketone bodies are detected by a dipstick. Testing for serum ketones is performed
if urine testing is positive, using nitroprusside (Acetest) tablets or reagent sticks. A 4+
reaction with serum diluted 1:1 is strongly suggestive of ketoacidosis.
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Serum Sodium
The measured serum sodium concentration in uncontrolled diabetes mellitus is
variable, as factors are present that can both lower and raise the measured value. The
final serum sodium concentration will reflect the balance between dilution of sodium
due to osmotic water movement out of the cells, and concentration of sodium due to
glucosuria-induced osmotic diuresis resulting in water loss in excess of sodium.
Physiologic calculations suggest that the serum sodium concentration should
fall by 1 mEq/L for every 62 mg/dL (3.5 mmol/L) rise in the serum concentration of
glucose. However, this standard correction factor was not verified experimentally and
in the setting of DKA and HHNK, a ratio of 2.4 mEq/L for every 100 mg/dL of glucose
rise is more appropriate.32
Remember, some patients with uncontrolled diabetes have marked hyperlipidemia
and lactescent serum. In this setting, each liter of serum contains less water and
therefore less sodium and the measured serum sodium concentration will fall, even
though the physiologically important serum water sodium concentration and plasma
osmolality are not affected.
Serum Potassium
Patients with DKA or HHNK, at presentation, have a potassium deficit that averages
35 mg/kg. A number of factors contribute to this deficit, particularly increased
urinary losses due both to the glucose osmotic diuresis and to the need to maintain
electroneutrality as ketoacid anions are excreted. Gastrointestinal losses and the loss
of potassium from the cells due to glycogenolysis and proteolysis also may play a
contributory role.33
Despite these potassium losses, the serum potassium concentration is usually
normal or, in one-third of patients, elevated on admission. It is thought that
hyperosmolality and insulin deficiency are primarily responsible for the relative
rise in the serum potassium concentration in this setting. Insulin therapy lowers the
potassium concentration and may cause severe hypokalemia, particularly in patients
with a normal or low serum potassium concentration at presentation.34 Thus, careful
monitoring and timely administration of potassium supplementation are essential.
Serum Phosphate
Patients with uncontrolled hyperglycemia are typically in negative phosphate balance
because of decreased phosphate intake and phosphaturia caused by osmotic diuresis.
Despite phosphate depletion, the serum phosphate concentration at presentation is
usually normal or even high because both insulin deficiency and metabolic acidosis
cause a shift of phosphate out of the cells.35
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be based upon clinical findings and imaging. The mechanisms for hyperamylasemia
and hyperlipasemia in DKA are not well defined.36
Leukocytosis
The majority of patients with hyperglycemic emergencies present with leukocytosis,
which is proportional to the degree of ketonemia. Leukocytosis unrelated to infection
may occur as a result of hypercortisolemia and increased catecholamine secretion.
However, a white blood cell count greater than 25,000/microL or a band count greater
than 10 percent may designate infection and indicates a need for further work-up.37
Lipids
Patients with DKA or HHS may present with marked hyperlipidemia and lactescent
serum. In a study of 13 patients with DKA, the mean plasma triglyceride and
cholesterol levels on admission were 574 mg/dL (6.5 mol/L) and 212 mg/dL (5.5
mmol/L), respectively. Triglycerides fell below 150 mg/dL (1.7 mmol/L) in 24 hours
with insulin therapy.38
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of metabolic acidosis should include high fat intake, lactic
acidosis, alcoholic acidosis, salicylate poisoning and the most important in the month
of fastingfasting ketoacidosis.
Fasting Ketoacidosis
This is the major differential diagnosis to rule out in the fasting patient in Ramadan.
Mostly ketoacid levels in fasting ketoacidosis do not exceed 10 mEq/L with prolonged
fasting alone, which means that the serum bicarbonate concentration is typically
above 14 mEq/L.39
TREATMENT
Once the diagnosis of DKA and HHNK is established on the basis of history, physical
examination, and laboratory work-up, treatment should be undertaken promptly and
in an organized fashion. A flow chart should be made in order to keep track of all
treatment steps, blood sugars, and electrolyte balance as under or over treatment can
result in devastating consequences.
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Give several liters of isotonic (0.9%) saline as rapidly as possible to patients with
signs of shock.
Give isotonic saline at 1520 mL/kg/hour, in the absence of cardiac compromise,
for the first few hours to hypovolemic patients without shock.
After intravascular volume is restored, give one-half isotonic (0.45%) saline at 4
to 14 mL/kg/hour if the corrected serum sodium is normal or elevated; isotonic
saline is continued if the corrected serum sodium is reduced.
Add dextrose to the saline solution when the serum glucose reaches 200 mg/dL
(11.1 mmol/L).
Regardless of the initial measured serum potassium, patients with DKA have a
large total body potassium deficit.
If initial serum K+ is below 3.3 mEq/L, hold insulin and give K+ 2030 mEq/hour IV
until K+ concentration is above 3.3 mEq/L.
If initial serum K+ is between 3.3 and 5.3 mEq/L, give K+ 2030 mEq/liter IV fluid;
maintain K+ between 4 and 5 mEq/L.
If initial serum K+ is above 5.3 mEq/L do not give K+; check K+ every 2 hours.
Give Insulin
Do not give insulin if initial serum K+ is below 3.3 mEq/L; replete K+ first.
Give all patients without a serum K+ below 3.3 mEq/L regular insulin. Either of two
regimens can be used: 0.1 units/kg IV bolus, then start a continuous IV infusion 0.1
units/kg/hour; or do not give bolus and start a continuous IV infusion at a rate of
0.14 units/kg/hour.
Continue insulin infusion until ketoacidosis is resolved, serum glucose is below
200 mg/dL (11.1 mmol/L), and subcutaneous insulin is begun.
If the arterial pH is between 6.90 and 7.00, give 50 mEq of sodium bicarbonate plus
10 mEq of potassium chloride in 200 mL of sterile water over 2 hours.
If the arterial pH is below 6.90, give 100 mEq of sodium bicarbonate plus 20 mEq
of potassium chloride in 400 mL sterile water over two hours.
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PREVENTIVE MEASURES
All diabetics who are planning to observe the fasting in the month of Ramadan should
be comprehensively educated about the possibility of developing DKA and HHNK.
Their medications should be evaluated and all the necessary changes should be made
before the onset of Ramadan mostly decrease in the dose of insulin, type of insulinlong acting versus premix, decrease in the dose of sulfonylureas. Especial emphasis
should be placed on hydration status and early recognition of any signs or symptoms
of DKA and HHNK.
CONCLUSION
Diabetic ketoacidosis and HHNK can be avoided in the month of Ramadan with
proper education of the patient, their relatives, and a close communication between
patient and their physicians. Sometimes, it is necessary to avoid fasting or break a
fast to avoid unacceptable consequences that can result from these complications.
Patients should be informed that their God is more interested in their being alive than
dead.
REFERENCES
1. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with
diabetes: a consensus statement from the American Diabetes Association. Diabetes Care.
2006;29(12):2739-48.
2. Kitabchi, AE, Umpierrez, GE, Miles, JM, Fisher, JN. Hyperglycemic crises in adult patients
with diabetes. Diabetes Care 2009;32:1335-43.
3. Arieff AI, Carroll HJ. Nonketotic hyperosmolar coma with hyperglycemia: clinical features,
pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria
and the effects of therapy in 37 cases. Medicine (Baltimore). 1972;51(2):73-94.
4. Kitabchi AE, Young R, Sacks H, et al. Diabetic ketoacidosis: reappraisal of therapeutic
approach. Annu Rev Med. 1979;30:339-57.
5. Wachtel TJ. The diabetic hyperosmolar state. Clin Geriatr Med. 1990;6(4):797-806.
6. Abbas E. Kitabchi, Guillermo E. Umpierrez, Mary Beth Murphy RN, Robert A. Kreisberg.
Hyperglycemic Crises in Adult Patients with Diabetes. Diabetes Care 2006;29(12):2739-48.
7. Kitabchi AE, Razavi L. Hyperglycemic crises: diabetic ketoacidosis (DKA), and
hyperglycemic hyperosmolar state (HHS). [online] Available from http://www.endotext.
org/diabetes/diabetes24/diabetesframe24.htm (Accessed on January, 2013).
8. Kitabchi AE, Umpierrez GE, Murphy MB. Diabetic ketoacidosis and hyperglycemic
hypersmolar state. In: DeFronzo RA, Ferrannini E, Keen H, Zimmet P (Eds). International
Textbook of Diabetes Mellitus, 3rd edition. Chichester, UK: John Wiley & Sons; 2004.
p.1101.
9. Wachtel TJ, Silliman RA, Lamberton P. Prognostic factors in the diabetic hyperosmolar
state. J Am Geriatr Soc. 1987;35(8):737-41.
10. Fishbein HA, Palumbo PJ. Acute metabolic complications in diabetes. In: Diabetes in
America. National Diabetes Data Group, National Institutes of Health; 1995. p. 283 (NIH
publ. no: 95-1468).
11. Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders, 5th edition,
New York: McGraw-Hill; 2001. p. 794.
186
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186
12. Unger RH, Orci L. Glucagon and the A cell: physiology and pathophysiology (first two
parts). N Engl J Med. 1981;304(25):1518-24.
13. Diamond MP, Hallarman L, Starick-Zych K, et al. Suppression of counterregulatory
hormone response to hypoglycemia by insulin per se. J Clin Endocrinol Metab.
1991;72(6):1388-90.
14. Josefsberg Z, Laron Z, Doron M, et al. Plasma glucagon response to arginine infusion in
children and adolescents with diabetes mellitus. Clin Endocrinol (Oxf ). 1975;4(5):487-92.
15. DeFronzo RA, Matzuda M, Barret E. Diabetic ketoacidosis: a combined metabolicnephrologic approach to therapy. Diabetes Rev. 1994;2:209.
16. Wachtel TJ, Tetu-Mouradjian LM, Goldman DL, et al. Hyperosmolarity and acidosis
in diabetes mellitus: a three-year experience in Rhode Island. J Gen Intern Med.
1991;6(6):495-502.
17. Chupin M, Charbonnel B, Chupin F. C-peptide blood levels in keto-acidosis and in
hyperosmolar non-ketotic diabetic coma. Acta Diabetol Lat. 1981;18(2):123-8.
18. Hillman K. Fluid resuscitation in diabetic emergenciesa reappraisal. Intensive Care
Med. 1987;13(1):4-8.
19. Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders, 5th edition,
New York: McGraw-Hill; 2001. p. 794.
20. Foster DW. Banting lecture 1984. From glycogen to ketones--and back. Diabetes.
1984;33(12):1188-99.
21. SaccL, Orofino G, Petrone A, et al. Differential roles of splanchnic and peripheral tissues
in the pathogenesis of impaired glucose tolerance. J Clin Invest. 1984;73(6):1683-7.
22. Miles JM, Haymond MW, Nissen SL, et al. Effects of free fatty acid availability, glucagon
excess, and insulin deficiency on ketone body production in postabsorptive man. J Clin
Invest. 1983;71(6):1554-61.
23. Owen OE, Trapp VE, Skutches CL, et al. Acetone metabolism during diabetic ketoacidosis.
Diabetes. 1982;31(3):242-8.
24. Cook GA, Nielsen RC, Hawkins RA, et al. Effect of glucagon on hepatic malonyl coenzyme
A concentration and on lipid synthesis. J Biol Chem. 1977;252(12):4421-4.
25. Zierler KL, Rabinowitzd D. Effect of very small concentrations of insulin on forearm
metabolism. Persistance of its action on potassium and free fatty acids without its effect
on glucose. J Clin Invest. 1964;43:950-62.
26. Kitabchi AE, Murphy MB. Consequences of insulin deficiency. In: Skyler J (Ed). Atlas of
Diabetes, 4th edition, New York: Springer US 2012. p. 39.
27. Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a
comprehensive literature review. CNS Drugs. 2005;19(Suppl 1):1-93.
28. Polonsky WH, Anderson BJ, Lohrer PA, et al. Insulin omission in women with IDDM.
Diabetes Care. 1994;17(10):1178-85.
29. Popli S, Leehey DJ, Daugirdas JT, et al. Asymptomatic, nonketotic, severe hyperglycemia
with hyponatremia. Arch Intern Med. 1990;150(9):1962-4.
30. Malone ML, Gennis V, Goodwin JS. Characteristics of diabetic ketoacidosis in older versus
younger adults. J Am Geriatr Soc. 1992;40(11):1100-4.
31. Adrogu HJ, Wilson H, Boyd AE, et al. Plasma acid-base patterns in diabetic ketoacidosis.
N Engl J Med. 1982;307(26):1603-10.
32. Katz MA. Hyperglycemia-induced hyponatremiacalculation of expected serum sodium
depression. N Engl J Med. 1973;289(16):843-4.
33. Adrogu HJ, Lederer ED, Suki WN, et al. Determinants of plasma potassium levels in
diabetic ketoacidosis. Medicine (Baltimore). 1986;65(3):163-72.
34. Fulop M. Serum potassium in lactic acidosis and ketoacidosis. N Engl J Med.
1979;300(19):1087-9.
187
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Chapter
20
Dyselectrolytemia in Ramadan
Bashir Ahmad Laway, Nazir Ahmad Pala
Abstract
Ramadan fasting occurs at different seasons of the year because it depends upon the lunar calander.
Because of heat and humid conditions, many abnormalities in fluid, blood concentration and urinary
excretion of electrolytes have been reported in people with diabetes mellitus and diabetes insipidus,
though these may be within the normal limits. Sodium excretion declines throughout Ramadan and
increases in the 1st week after Ramadan. However, serum sodium does not change beyond normal
limits. Similarly there is some decline in potassium excretion during Ramadan and reverts back to prefasting level after. Some changes in serum concentration of calcium have been reported, some have
reported decrease while others have reported a minor increase. People with chronic kidney disease
(CKD) are predisposed to severe hyperkalemia because of uncontrolled diabetes and consumption of
high carbohydrate meal. People with diabetes insipidus are predisposed to severe dehydration and
hypernatremia during the month of Ramadan fasting.
INTRODUCTION
189
189
190
190
Diabetes Insipidus
Conservation of body fluid resources and balancing outer-cell liquid with intertissue spaces is crucial. Osmolality, which is the sign of osmosis activity of all plasma
particles, is between 280 mOsm/kg and 295 mOsm/kg. Changes in the body fluid
status and the amount of outer cell sodium can lead to many changes in plasma
osmolality.20 Changes in plasma osmolality of about 12% stimulate osmoreceptors
which cause the discharge of antidiuretic hormones and stimulation of thirst.21
Because thirst is preserved in patients with diabetes insipidus, plasma osmolality is
usually maintained within the normal range, and hypernatremia usually indicates
poor fluid intake than severe renal water loss.22 During Ramadan fasting, Muslims
abstain from food and drink for about 1218 hours which may lead to increase in
plasma osmolality, sodium and uric acid because of dehydration.12 This effect will be
more pronounced in athletes, manual laborers, in individuals who fast during summer
and is more pronounced in tropical areas. With fluid restriction during the day, in
Ramadan, coupled with continuing polyuria in patients with diabetes insipidus,
severe dehydration and hypernatremia can occur which has devastating effects on
central nervous system.23
Diabetes Mellitus
There are no major problems encountered with Type 2 diabetes (T2D) and even
controlled Type 1 diabetes(T1D) patients during Ramadan fasting.24,25 Some
abnormalities in fluid and electrolyte balance are common biochemical findings
in diabetes mellitus and have been attributed to increased losses, reduced intake/
absorption or alterations in metabolism.26,27 In diabetes mellitus, increased urinary
loss due to osmotic diuresis may be a common and most important cause of reduced
electrolytes, although intracellular shift also plays a role.26 The extensive EPIDIAR
191
191
CONCLUDING REMARKS
192
192
Patients with T2D and controlled T1D have no major problems with fasting.
However, patients with poor glycemic control are at increased risk of development
of hyperkalemia, hyponatremia and hypomagnesemia.
Patients with uncontrolled diabetes mellitus and CKD are at risk of life-threatening
hyperkalemia.
Patients of diabetes insipidus, with large volumes of polyuria, can develop
profound dehydration with severe hypernatremia which can be fatal.
RECOMMENDATIONS
Patients with diabetes mellitus should avoid the practice of consumption of large
quantities of carbohydrates and fruit juices in the non-fasting hours. Calories
should be distributed in two to three meals to prevent postprandial hyperglycemia
and subsequent risk of electrolyte disturbances.
Fasting should be interrupted if blood glucose exceeds more than 300 mg/dL and
avoided on sick days.
Fluid intake (water) should be increased during non-fasting hours
Normal levels of physical activity may be maintained, multiple prayers should be
considered as a part of exercise program.
Renal transplant recipients with normal allograft function can observe fast without
additional risks
Patients with CKD should be cautioned about the potential risk of developing
hyperkalemia and their renal function and electrolytes should be monitored and
should stop fasting if deterioration occurs.
Diabetic patients on dialysis with uncontrolled glycemia should not fast because
of increased risk of life threatening hyperkalemia.
Patients with mild polyuria can fast without significant electrolyte abnormalities.
Patients with large volume of polyuria should not fast and if they insist, should be
monitored closely. If they lose more than 3% of body weight or if serum sodium
rises above normal, should break their fast.
REFERENCES
1. Sakr AH. Fasting in Islam. J Am Diet Assoc. 1975;67:17-21.
2. Azizi F. Medical aspects of Islamic fasting. Medical J Islamic Rep Iran.1996;10:241-6.
3. Cheah SH, Chng SL, Hussein R, et al. Effects of fasting during Ramadan on urinary
excretion in Malaysian Muslims. Br J Nutr. 1990;63:329-37.
4. Atlas SA, Laragh JH. Atrial natriuretic peptide: a new factor in hormonal control of blood
pressure and electrolyte homeostasis. Annual Review of Medicine. 1986;37:397-414.
5. Carey RM, Sen S. Recent progress in the control of aldosterone secretion. Recent Progress
in Hormone Research. 1986;42:251-96.
6. Azizi F, Rasouli HA. Serum glucose, bilirubin, calcium, phosphorus, protein and albumin
concentrations during Ramadan. Med J Islamic Rep Iran. 1987;1:38-41.
7. El-Hazmi MA, Al-Faleh FZ, Al-Mofleh IB. Effect of Ramadan fasting on the values of
hematological and biochemical parameters. Saudi Med J. 1987;8:171-6.
8. Chill GF. Starvation in man. N Engl J Med. 1970;282:668-75.
9. Heber D. Starvation and nutrition therapy. In: DeGroot LJ, Jameson JL (Eds). Endocrinology,
4th edition, Vol. 1. Philadelphia: WB Saunders; 2001 pp. 642-5.
193
193
10. Kerndt PR, Naughton JL, Driscoll CE, et al. Fasting: The history, pathophysiology and
complications (Medical Progress). West J Med. 1982;137:379-99.
11. Miladipour AH, Shakhssalim N, Parvin M, et al. Effect of Ramadan fasting on urinary risk
factors for calculus formation. Iran J Kidney Dis. 2012;6(1):33-8.
12. Prentice AM, Lamb WH, Prentice A, et al. The effect of water abstention on milk synthesis
in lactating women. Clin Sci (Lond.) 1984;66:291-8.
13. Bernieh B, Al-Hakim MR, Boobes Y, et al. Fasting Ramadan in chronic kidney disease
patients: Clinical and biochemical effects.
14. El-Wakil H, Desoky I, Lotfy N, et al. Fasting the month of Ramadan by Muslims: Could it be
injurious to their kidneys? Saudi J Kidney Dis Transpl. 2007;18:349-54.
15. Eknoyan G, Lameire N, Barsoum R, et al. The burden of kidney disease: improving global
outcomes. Kidney Int. 2004;66:1310-4.
16. Al-khader A, Al-Hsani M, Dhar J, et al. Effect of diet during Ramadan on chronic
hemodialysis. Saudi Med J. 1991;12:30-1.
17. Montoliu J, Revert L. Lethal hyperkalemia associated with severe hyperglycemia in
diabetic patients with renal failure. Am J Kidney Dis.1985;5:47-8.
18. Gifford JD, Rutsky EA, Kirk KA, et al. Control of serum potassium during fasting in patient
with end stage renal disease. Kidney Int. 1989;35:90-4.
19. Abdalla AH, Shaheen FA, Rassoul Z. Effect of Ramadan fasting on Muslim kidney
transplant recipients. Am J Nephrol. 1998;18:101-4.
20. Grimshaw P. Sport and exercise biomechanics. 4th edition. New York: Taylor & Francis
Group: BIOS instant notes; 2006.
21. Baylis PH, Thompson CJ. Osmoregulation of vasopressin secretion and thirst in health and
disease. Clin Endocrinol (Oxf ) 1988;29:549-76.
22. MIXES, M. (1984) Clinical and laboratory features of central and nephrogenic diabetes
insipidus and primary polydipsia. In: The Neurohypophysis. Reichlin S (Ed.). New York:
Plenum Press; pp.115-38.
23. Robinson AG, Verbalis JG, Diabetes Insipidus. Melmed S, Polonsky KS, Larsen PR,
Kronenberg HM eds. In: Williams Textbook of Endocrinology; 12th Edition, Elsevier;
Philadelphia: p.291-323.
24. Ramadan fasting and its effect on the metabolic control of diabetes. Pract Diabetes.
1987;4:287-90.
25. Sulimani RA, Laajam M, Al-Attas O, et al. The effect of Ramadan fasting on diabetes control
in type II diabetic patients. Nutr Res. 1991;11:261-4.
26. Hebden RA, Gardiner SM, Bennett T, et al. The influence of streptozotocin-induced diabetes
mellitus on fluid and electrolyte handling in rats. Clin Sci (London). 1986;70(1):111-7.
27. Macallan DC. Wasting in HIV infection and AIDS. J Nutr. 1999;129:238S-242S.
28. Salti I, Benard E, Detournay B, EPIDIAR study group, et al. A population based study
of diabetes and its characteristics during the fasting month of Ramadan in 13 countries:
results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study.
Diabetes Care. 2004;27:2306-11.
29. Goldfarb S, Cox M, Singer I, et al. Acute hyperkalemia induced by hyperglycemia:
Hormonal mechanisms. Ann Intern Med. 1976;84:426-32.
30. Ammon R, May W, Nightingale S. Glucose-induced hyperkalemia with normal aldosterone
levels-Studies in a patient with diabetes mellitus. Ann Intern Med. 1978;89:349-35.
31. Zierler KL. Effect of insulin on potassium efflux from muscle in the presence and absence
of glucose. Is J Physio. 1966;198:1066-70.
32. McNair P, Madsbad S, Christiansen C, et al. Hyponatremia and hyperkalemia in relation to
hyperglycemia in insulin-treated diabetic out-patients. Clin Chim Acta. 1982;120:243-50.
33. Perez GO, Lespier L, Jacobi J, et al. Hyporeninemia and hypoaldosteronism in diabetes
mellitus. Arch InternMed. 1977;137:652-7.
194
194
34. Makoff DL, Da Silva JA, Rosenbaum BJ. On the mechanism of hyperkalemia due to
hyperosmotic expansion with saline or mannitol. Clin Sci (London). 1971;41:383-93.
35. Androgue HJ, Madias NE. Changes in plasma potassium concentration during acid-base
disturbances. AmJ Med. 1981;71:456-67.
36. Rose BD. Hyperosmolal states-hyperglycemia. In: Rose BD, Post TW (Eds). Clinical
physiology of acid-base and electrolyte disorders. 5th edition. New York: MacGraw Hill;
2001:794-821.
37. Lorber D. Nonketotic hypertonicity in diabetes mellitus. Med Clin North Am. 1995;79:
39-52.
38. Djurhuus MS, Skott P, Vagg A, et al. Hyperglycemia enhances renal magnesium excretion
in type 1 diabetic patients. Scand J Clin Lab Inves. 2000;60:403-9.
39. Resnick LM, Gupta RK, Bhargava KK, et al. Cellular ions in hypertension, diabetes and
obesity: a nuclear magnetic resonance spectroscopic study. Hypertension. 1999;17:951-7.
Chapter
21
Management of Diabetic
Patients with Co-morbid
Conditions during Ramadan
Mahdi Kamoun, Ines Slim, Mouna Feki Mnif
Abstract
Patients with chronic diseases often insist on fasting even though they are permitted not to by Islamic
rules. Recent studies corroborate safety of Ramadan fasting in diabetic patients with stable comorbidities; especially if they had a pre-Ramadan medical assessment and educational counseling. In such
patients, medical advices regarding medications schedules, drug interactions and nonpharmacological
measures should be provided. Sustained release formulations may be of particular interest during
Ramadan. However, fasting may lead to severe alterations in patients with more serious cardiovascular
and renal diseases.
The aim of this chapter is to provide a comprehensive review of the Ramadan management of
diabetic patients with selected co-morbid conditions (hypertension, dyslipidemia, cardiovascular
disease and kidney disease). The effects of fasting during Ramadan on this specific population are
also briefly described.
INTRODUCTION
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Fasting Safety
Fasting that endangers health is not in accordance with Islamic jurisprudence. The
Quran states exemption from fasting for patients with chronic diseases if fasting
worsens ones illness or delays recovery. Physicians play a key role in the safety
assessment of Ramadan fasting in diabetic patients with comorbidities. In this
vulnerable population, fasting should have no deleterious impacts on both the
diabetes and its associated comorbidities. It is important to know whether fasting will
increase mortality risk, cause a significant morbidity (organ failure, complications),
or lead to excessive pain and difficulty. In addition, physicians need to determine
whether or not it is safe to fast during periods of stability of the chronic illness of their
patients.
Overall; diabetic patients with comorbidities could be divided into three categories
(Flow chart 1):
1. Patients who are not harmed by fasting (such as well-controlled Type 2 diabetic
patients with stable comorbidities). Such patients could be advised to fast in
Ramadan.
2. Patients who are not harmed by fasting but their treatment could be adjusted for
proper control (such as antihypertensive medications).
3. Patients who are harmed by fasting or their treatment cannot be given with fasting
(such as acute myocardial infarction). Such patients should avoid Ramadan fasting.
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fasting, hence their efficacy and tolerance is decreased. This is especially relevant for
drugs with a narrow therapeutic index such as digoxin.1
Drug Interactions
Physicians should be aware of drug interactions during Ramadan. There is a high
risk of such interactions in diabetic patients with comorbidities who often take
simultaneously their daily medicines either at sunset (Iftar) or at sunrise (Suhur). As
examples, amiodarone and spironolactone can increase digoxin levels and the risk
of toxicity. The co-administration of digoxin and beta-blockers or calcium-channel
blockers (verapamil), which also reduces heart rate, can cause serious slowing of the
heart rate. Diuretic-induced reduction in blood potassium or magnesium levels may
predispose patients to digoxin-induced abnormal heart rhythms.1
Dosing Schedule
Since drug doses can be taken only between sunset and dawn during fasting, and
the time span between them is shorter than outside Ramadan, most medications
schedules should be altered. Two different types of dosage schedule are commonly
used during Ramadan.1
Drug-Food Interactions
Drug-food interactions may result in reduced, delayed, or increased systemic
availability of a drug. Risk of such interactions may be also increased during Ramadan.
For example, grapefruit juice may reduce the breakdown of amiodarone in the
stomach leading to increased amiodarone blood levels. Differently, the bioavailability
of celiprolol diminishes when taken along with orange juice by possible mechanisms
related to pH variations and changes in the function of the transporters in the
intestine.4
The degree of interaction, and whether it positively or negatively affects drug
absorption, depends on several factors, including the physical and chemical nature of
the drug, the formulation, the type of meal, and the time interval between eating and
dosing. Particular care should be taken in using drugs that have to be administered on
an empty stomach.1
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Figure 1: Twenty-four hours blood pressure monitoring in 45 patients with grade 23 hypertension.
Measurements were taken in the month of Ramadan (solid lines) and in the following month (dotted
line). Vertical axis: blood pressure as mm Hg, horizontal axis: time as hours. No statistically significant
difference was found between 24-hour mean blood pressures in the two monitoring periods, except
for a small rise before dawn while having a morning meal6
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Patients should be encouraged to seek medical advice before fasting to adjust the doses
of their medications
Patients should be advised and educated about the importance of strict compliance with
nonpharmacological measures and antihypertensive therapy
Where diuretic therapy is necessary, the drug should be reduced and administered after
the evening meal
Patients with difficult to control hypertension should be advised not to fast until their
blood pressure is reasonably controlled
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Therefore, such regimen (drug intake twice: before fasting and after the breaking
fast) seems to be a suitable alternative in patients with grade 23 hypertension
using combination drug therapy.6
Nonpharmacological measures.
Dietary salt restriction should be advised for patients with hypertension. Drinks
in Ramadan have become part of the months traditions. Licorice, a popular drink
in many Arab countries during Ramadan, has been associated with an elevation in
BP and or exacerbation of hypertension.10 It inhibits the enzyme 11--hydroxysteroid
dehydrogenase enzyme type 2 with a resultant cortisol-induced mineralocorticoid
effect and the tendency towards the elevation of sodium and reduction of potassium
levels. Therefore, avoiding or at least reducing licorice consumption is recommended.11
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Pharmacological measures
Anti-ischemic drugs: Anti-ischemic drugs include oral nitrates, calcium
channel blockers, and -Adrenoceptor antagonist. Both pharmacokinetics and
pharmacodynamics of these medications have been shown to be influenced by the
circadian time of their administration. For examples, plasma peak concentrations
of nifedipine, oral nitrates and propranolol are twice as high and time to reach
peak concentrations are shorter after morning dosing compared with evening
dosing. Such a variation was not detected when extended release dosage forms of
nifedipine and isosorbide mononitrate were used. The underlying mechanisms of
their chronopharmacokinetic pattern may involve a faster gastric emptying time
and higher gastrointestinal perfusion in the morning.18
Shiga et al. documented that atenolol, in contrast to propranolol, is not
absorbed more rapidly after morning administration compared with post-evening
administration. This confirms that most lipophilic, but not hydrophilic, drugs
seem to be absorbed faster in the morning as compared to evening.19
Antiarrhythmic drugs: Amiodarone is the most widely prescribed antiarrhythmic
medication. It may be administered once daily or given twice daily with meals to
minimize stomach upset which is seen more frequently with higher doses. During
Ramadan, amiodarone can be taken either at Iftar or at Suhur. There are a number
of important drug interactions with amiodarone. For examples, amiodarone may
interact with beta blockers or certain calcium-channel blockers, such as verapamil
and diltiazem resulting in a very slow heart rate or a block in the hearts electrical
conduction system. Amiodarone increases also the blood levels of digoxin when
the two drugs are given together. Patients fasting Ramadan are at particularly
high risk for the amiodarone drug interactions, as they tend to take their drugs
simultaneously.
Heart failure drugs: Cardiac glycosides (digoxin and digitoxin) have a
narrow therapeutic range and changes in their pharmacokinetics and/or
pharmacodynamics due to drug-interactions can result in toxicity (see above).
There are no significant changes in the pharmacokinetics of digoxin when ingested
in the morning versus evening. When digoxin tablets are taken after meals, the
rate of absorption is slowed, but the total amount of digoxin absorbed is usually
unchanged.20 Consequently, during Ramadan, this drug can be taken either at
Suhur or at Iftar. Heart failure patients should use diuretics after Iftar and those
with severe CHF requiring high doses of diuretics should be counselled against
fasting.
Anticoagulation drugs: Ramadan fasting has been shown to have some
hematological effects such as a reduction in the hematocrit and a decrease
response of platelets to different aggregating agents [adenosine diphosphate
(ADP), collagen and adrenaline]. These effects are associated with the prolongation
of bleeding and coagulation times. However, in a study in patients with
cardiovascular disease, fasting did not appear to influence the dose or the effect of
warfarin anti-coagulation. Shifting from daytime to night-time administration of
a long-acting anti-coagulant does not adversely affect the anticoagulant process
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and does not increase the incidence of thromboembolic events and hemorrhagic
complications.21
Nonpharmacological measures: Adequate dietary habits and weight loss should
be advised for appropriately selected patients with cardio-metabolic diseases.
Fluid restriction (1.5002.000 mL) as well as the control of sodium intake
(< 2 g) are relevant in patients with advanced heart failure. It should also be
advised that salt substitutes must be used with caution, as they may contain
potassium. In large quantities, in combination with an ACE-inhibitor, they may
lead to hyperkalemia.22,23
Food may affect the bioavailability of some cardiovascular drugs and in some
specific cases, such as dairy products and rich-inprotein diets, this should be
carefully considered during Ramadan month. Grapefruit may enhance drug toxicity
for antiarrhythmic agents such as amiodarone.24 Therefore, patients taking oral
amiodarone should avoid grapefruit juice. Regular exercise should be advocated in
stable patients with CVD. The congregational night prayers of the month of Ramadan
constitute appropriate level of physical activity equivalent to moderate physical
activity.25
Cigarette smoking should be strongly discouraged in patients with CVD. Ramadan
provides an excellent opportunity to give up smoking.
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Such beneficial effect may be explained by the favorable impact of Ramadan fasting
on stress oxidative parameters.29 However, these patients should be advised to reduce
their protein intake, as high protein intake may promote renal damage by chronically
increasing glomerular filtration rate.30 Ramadan fasting may have unfavorable impact
on patients with more advanced stage of kidney disease. A prospective observational
study evaluated the effect of Ramadan fasting in 36 patients with moderate to severe
renal insufficiency during and 2 weeks after the fasting event. There was a significant
deterioration of renal function parameters which persisted for 2 weeks after the end
of Ramadan. In nine patients, there was also a progressive fluid retention, weight
gain, lower limb edema, and poor control of BP, requiring frequent adjustment of
management. These findings suggest that, in patients with moderate to severe renal
impairment, Ramadan fasting may be associated with further deterioration in renal
function which may become irreversible and cause adverse serious health problems.31
Only one single study of 40 patients receiving hemodialysis treatment for more
than 6 months examined the effect of fasting during Ramadan. Patients fasted on
nondialysis days. An interdialytic weight gain and a significant rise in serum K+ levels
occurred, but with no change in BP. However, no hospitalization for pulmonary edema
or for the adverse effects hyperkalemia was required. Based on these observations,
the authors recommended that fasting on nondialysis days is probably safe and that
dietary advice in fasting patients assumes increasing importance.32 Further studies
may be required to draw firm conclusions.
Ramadan fasting appears to be safe and not associated with adverse reactions
in renal transplant recipients with stable normal or stable impaired renal allograft
function.33,34 Boobes et al. studied 22 kidney transplant patients with stable kidney
functions, who were transplanted for more than one year, and voluntarily chose to fast
during Ramadan. Body weight, BP, renal and metabolic parameters and cyclosporine
levels remained stable after Ramadan fasting. The authors concluded that Ramadan
fasting is safe for kidney transplant recipients of more than one year with stable graft
function.35 Based on these preliminary findings, there is general agreement from
medical professionals that kidney transplant patients are allowed to fast in Ramadan
when the transplanted kidney graft is functioning well for at least 1 year.36
There is no enough evidence in favor of increased risks of calculus formation during
Ramadan fasting.37 Previous studies demonstrated significant correlations between
the occurrence of urinary renal colic and the hot seasons but not with Ramadan.38,39
Thus, it is important to emphasize adequate hydration between sunset and sunrise for
patients with previous history of renal calculus.
CONCLUSION
Diabetic patients with stable comorbidities may be allowed to fast in Ramadan under
proper medical supervision. In such patients, medical advices regarding medications
schedules, drug interactions and nonpharmacological measures should be provided.
Sustained release formulations may be of particular interest during Ramadan. However,
fasting may lead to severe alterations in patients with more serious cardiovascular and
renal diseases. Further studies should be carried out to provide more guidelines about
the management of diabetic patients with co-morbid conditions in Ramadan.
Section21:
5: Management
Management of
of Diabetic
Complications
Patients with Co-morbid Conditions ...
205 Chapter
205
ACKNOWLEDGMENTS
We are thankful to Dr Basma Ben Naceur, Nadia Charfi, Fatma Mnif, Mohamed
Dammak, Nabila Rekik, Mohamed Habib Sfar, Larbi Chaieb, Mohamed Abid for their
contribution in the preparation of this manuscript.
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Index
Page numbers followed by f refer to figure and t refer to table
Causes of stress in Ramadan 86
A
Caveats regarding insulin therapy 122
Abdominal pain 72
Chlorpropamide 97
in diabetic ketoacidosis 179
Chronic
Acarbose 97
dialysis 41, 43, 128, 145
Activated protein kinase 54
kidney disease 190, 195, 197, 203
Acute
Circumstances of fasting 23
cardiovascular events 49
Complications of fasting 117
diabetic complications 46
Congestive heart failure 197, 201
illness 41, 43, 127
Continuous subcutaneous infusion 77
peptic ulcer 41
Adenosine diphosphate 202
Advanced glycation endproducts 47
D
Agglomerated vesicle technology 123
Dehydration 118
Airway, breathing and circulation status
and Ramadan 83
178, 184
and thrombosis 9, 40, 72, 144
Alpha-glucosidase inhibitors 101, 123, 160
Diabetes
American Diabetes Association 80, 159, 165, 174
and fasting during Ramadan 68
Angiotensin
insipidus 190
converting-enzyme inhibitors 200
mellitus 22, 190
receptor blockers 200
Diabetic ketoacidosis 9, 40, 72, 117, 121, 144, 176
Anion gap
Dietary stress 90
acidosis 183
Digestive system 51
metabolic acidosis 181
Dipeptidyl peptidase-4 inhibitors 108, 123
Anthropometric parameters 46, 47
Dry
Antiarrhythmic drugs 202
mouth 72
Anticoagulation drugs 202
tongue and skin 72
Anti-ischemic drugs 202
Dyselectrolytemia in Ramadan 188
Dyslipidemia and Ramadan fasting 201
B
Biguanides 96, 97, 99
Blood
glucose monitoring 169
pressure 48, 106
Body weight 69
Brain-derived neurotrophic factor 30, 50, 52, 53
Breaking fast 18, 158
C
Calcium-channel blockers 200
Cancer 41
Carbohydrate 25
Cardiovascular disease 195, 197
and Ramadan fasting 201
E
Endocrine glands 25
Endocrinology of fasting 22
in diabetic patient 32f, 33f
Engorgement of veins 73
Epidemiology of diabetes and Ramadan
23, 68, 106
Exercise
dehydration and Ramadan 82
diet controlled diabetes and Ramadan 81
hyperglycemia and Ramadan 81
hypoglycemia and Ramadan 81
physical labor and Ramadan 82
sportsmanship and Ramadan 80
208
F
Family counseling 15
Fasting
blood glucose 48
ketoacidosis 183
safety 196
Fatigue 72
Feeding roster 15
First generation SU 97
Follicular-stimulating hormone 28
Frequent
blood sugar monitoring 75
micturition 72
urination 72
Fructosamine 64
G
Gliclazide 97
Glimepiride 97
Glipizide 97
Glitazones 159
Glucagon-like peptide 1 106, 132
Glyburide 97, 167
Glycated hemoglobin 119
Glycemic
excursion response 18
targets 170
Glycosylated hemoglobin 64
Growth hormone 28
H
Headache 72
Heat shock proteins 49
Hemodialysis 203
Hepatic dysfunction 41
High density lipoprotein 70, 106
History of
recurrent hypoglycemia 43
religious fasting 23
Hyperglycemia 9, 18, 40, 41, 71, 72, 117, 144, 177
Hyperglycemic
emergencies in Ramadan 174
hyperosmolar
nonketotic state 175, 176
syndrome 174
Hyperosmolar hyperglycemic coma 43
Hypertension 195
and Ramadan fasting 199
Hypoglycemia 9, 18, 40, 41, 71, 118, 127, 144, 168
associated autonomic failure 168
unawareness 41, 43, 171
I
Importance of
osmotic diuresis 179
self-monitoring of blood glucose 120
Incretin-based therapy 160
Inflammation and oxidative stress 48
Insulin
and blood glucose monitoring during
Ramadan 137
and oral antidiabetic drugs in Ramadan
132, 133
continuation and Ramadan 129, 131t
counseling and Ramadan 128
excess 169
family therapy and Ramadan 137
glucagon-like peptide-1 and Ramadan 132
hyperglycemia and Ramadan 136
hypoglycemia and Ramadan 136
in Type 2 diabetes mellitus 126, 147
initiation and Ramadan 130t
intensification and Ramadan 133t
like growth factor 1 54
optimization and Ramadan 130, 131
pregnancy and Ramadan 134, 135
pump 121
and Ramadan 135
therapy 147
receptor substrate 54
regimens 121, 170
weight and Ramadan 136
International Diabetes Federation Guidelines 62
Itchy skin 73
K
Ketoacidosis 177
Kidney disease and Ramadan fasting 203
Kussmauls breathing 72
L
Lactation and Ramadan 153
Lethargy 72
Leukocytosis 183
Loss of
concentration 72
consciousness and coma 72
Low-density lipoprotein 106, 170
cholesterol 47
Luteinizing hormone 28
Index
M
Management of
cardiovascular diseases during Ramadan 202
diabetic
during Ramadan 73
patients with co-morbid conditions
during Ramadan 195, 199
hypertension during Ramadan fasting
200, 200t
Mean
amplitude of glycemic excursion 79
post-prandial glycemic excursion 79
Meglitinides 97, 98
Metformin 97, 159
Micro- and macrovascular diabetic
complications 47f
Modernization stress 90
Monitoring glucose values in Ramadan 17t
Muscle cramps 72
Myocardial ischemia 184
N
Nateglinide 97
Nausea 72
and vomiting 72
Neuroendocrine effects of Ramadan fasting 30
Nitric oxide 50
Nocturnal hypoglycemia 168
Nonketotic hyperosmolar hyperglycemia 62
R
Renal
function 51
insufficiency 43
stone disease 203
transplantation recipients 203
Replete
fluid deficit 184
potassium deficits 184
Risk of
hyperglycemia 33f
hypoglycemia 32f
O
Oral
antidiabetic drugs 97, 102
hypoglycemic 170
Overt cardiovascular diseases 41
P
Pathophysiology of fasting in diabetes 69f
Phosphatidylinositol 3-kinase 54
Physical activity in Ramadan 54, 79
Pioglitazone 97
Pneumonia 184
Pre-exercise evaluation and Ramadan 80
Pregnancy and
lactation 19, 44
Ramadan 19, 150
Pre-Ramadan
considerations in diabetics 70
counseling 12
and stress 87
medical assessment 119, 146, 158
209
Prominent veins 73
Psychosocial advantages of Ramadan fasting 86
Pulmonary tuberculosis 41
Ramadan 4
education and awareness in diabetes
program 62
fasting and
brain health 52 cancer
risk 52 cardiovascular
health 49 fertility 52
immunity 52
nutritional status 53
fasting in
children and adolescents 143
elderly 156
women 149
logbook 64f
stress rejuvenation 19
S
Second generation SU 97
Self-monitored blood glucose 165
Self-monitoring of blood glucose 61, 122
Serum
ketones 180
phosphate 182
potassium 182
sodium 182
Severe
bronchial asthma 41
hyperglycemia 34
hypoglycemia 34, 43, 127, 166
infections 41
ketoacidosis 34
Sitagliptin and Ramadan fasting 109
Sleep stress 90
Sodium 189
Spectrum of hyperglycemic crises 176
210
Stress management
and diabetes in Ramadan 85
in diabetics during Ramadan 90t
Structured diabetes education 120
Sulfonylurea 32, 43, 96-98, 102, 106, 110, 112
Sunken eyes 72
T
Thiazolidinedione 96, 97, 100, 102, 106
Three dose insulin regimen 77
Thyroid-stimulating hormone 28, 29
Thyrotropin-releasing hormone 30
Tolbutamide 97
Traditional oral antidiabetic drugs 95, 96, 97t
Treatment of hypoglycemia 171
Triglycerides 106
Two dose insulin regimen 77, 174
Type
1 diabetes mellitus 15, 32, 42, 117, 119, 121
2 diabetes mellitus 32, 81, 96
U
Uric acid 70
Urinary infection 184
Use of
metformin in Ramadan 100
pioglitazone in Ramadan 101
V
Vascular endothelial growth factor 50
Very-low-density lipoprotein cholesterol 47
Vomiting 72
W
Warm skin 73
Warning signs 20
Weight loss 72