Pre-diabetes

About Pre-diabetes
Pre-diabetes, also known as impaired glucose tolerance (IGT) is a term used to describe people who are at increased risk of developing type 2 diabetes... More... Pre-diabetes, also known as impaired glucose tolerance (IGT) is a term used to describe people who are at increased risk of developing type 2 diabetes.1 These people have elevated blood glucose levels that are not high enough to fulfil the criteria for diabetes, yet are too high to be considered normal. Such a condition is characterised by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). IFG is defined as a fasting plasma glucose of 100-126 mg/dl (5.6-7.0 mmol/L) and IGT is defined as a plasma glucose level of >140 mg/dl (7.8 mmol/L) 2 hrs following a 75 g oral glucose challenge test.2,3 HbA1c levels are increasingly used for diagnosis of diabetes and it is also reasonable to consider an HbA1c range of 5.7-6.4% to be indicative of pre-diabetes.3 IFG and IGT should not be viewed as clinical entities in their own right, but rather as risk factors for the development of type 2 diabetes as well as cardiovascular disease and stroke.3 While individuals with pre-diabetes have a high risk of developing type 2 diabetes, the progression is not inevitable.1 Changes to diet and increases in the level of physical activity have been shown to prevent or delay diabetes and normalise blood glucose levels.3,4,5

Risk Factors for Pre-diabetes

Known risk factors for pre-diabetes include:3,4

Weight gain/obesity (particularly abdominal or visceral obesity) Inactivity Dyslipidemia (with high triglycerides and/or low HDL cholesterol) Hypertension Age The risk increases with age, especially after age 45 years, but the incidence of type 2 diabetes is increasing dramatically among children, adolescents, and younger adult Family history of type 2 diabetes in a first-degree relative Race History of gestational diabetes Polycystic ovary syndrome or other conditions associated with insulin resistance Inadequate sleep Several recent studies have linked lack of sleep to an increased risk of insulin resistance

Preventative Measures
The Diabetes Prevention Program conclusively showed that an alteration in diet coupled with an increase in physical activity can prevent the development of type 2 diabetes. In some cases, individuals with elevated blood glucose were even able to return blood glucose to within normal range.5,6,7

Challenges of Pre-diabetes

Population aging, sedentary patterns, and obesity are contributing to the marked increase in the prevalence of pre-diabetes

Under-utilisation of HbA1c screening or risk stratification Lack of sufficient data to accurately define normal glucose levels or IGT8

Type 1 Diabetes
About Type 1 Diabetes
Type 1 diabetes, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, accounts for approximately 5-10% of all diagnosed cases of diabetes... More... Type 1 diabetes, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, accounts for approximately 5-10% of all diagnosed cases of diabetes.1 Type 1 diabetes is an autoimmune disease characterised by insulin deficiency resulting from destruction of betacells in the pancreas. This form of diabetes usually affects children and young adults, but it can occur at any age.1 The incidence of type 1 diabetes appears to be increasing among children, but this is not the case in young adults.9 The exact cause of type 1 diabetes is unknown. The presence of certain genes can indicate an increased risk of developing type 1 diabetes; however, environmental factors may also be responsible for initiating or accelerating the ongoing autoimmune destruction of beta-cells.10

Risk Factors for Type 1 Diabetes

Known risk factors for type 1 diabetes include:

Family history Anyone with a parent or sibling with type 1 diabetes has a slightly increased risk11 Genetics Approximately 20 different genes have been identified which influence risk of developing type 1 diabetes.12 The most intensively studied are several genes located within the human leukocyte antigen (HLA) region of chromosome 6. At least two genes within the HLA region (HLA-DR and HLA-DQ) account for 40-50% of inherited diabetes risk.12 The presence of certain inherited variations of these two genes determines a persons overall risk of type 1 diabetes11 Early foetal events 10 o Blood incompatibility 10 o Maternal viral infections during pregnancy 10 o Early exposure to cows milk and other nutritional factors o Weight and growth Increased height, weight, weight for height, and BMI correlate with childhood onset diabetes10 o Lifestyle Habits related to improved welfare have been correlated with the incidence of childhood diabetes. It is well known that wealth can be a determinant of birth weight and childhood growth and therefore may be closely linked to diabetes onset10 o Geography The greatest incidence of type 1 diabetes is observed in southeast Asia where 24% of the estimated 480,000 children suffering from type 1 diabetes are located. European incidence is similar, reporting 23% of global type 1 paediatric cases. Complete global data however, are incomplete and in certain regions, such as sub-Saharan Africa, determining true incidence data is extremely difficult13

Preventative Measures
There is currently no known way to prevent type 1 diabetes.

Challenges of Type 1 Diabetes

Some of the challenges associated with type 1 diabetes include:

Defining type 1 diabetes Childhood diabetes is no longer restricted to type 1 diabetes. The incidence of type 2 diabetes in children is increasing14,15 and consequently differentiating diabetes type can be a challenge. Differentiation is crucial as treatment regimens may differ markedly Treating type 1 diabetes There is less clinical trial evidence supporting treatment recommendations for children and young adults with diabetes, so healthcare providers may need to rely more heavily upon empirical clinical experience to guide therapy. Physical growth and the onset of puberty may also result in changes in insulin sensitivity which can affect glycaemic control13 Treatment costs Treating type 1 diabetes in developing countries presents unique challenges to governments in terms of costs (e.g., insulin storage, needle supply, monitoring, etc.) Treatment access In less privileged families access to self-care tools and also insulin can be limited which can ultimately lead to severe handicap and early death 13 Psychosocial aspects Children and adolescents can find coping with diabetes emotionally difficult. The condition may cause embarrassment, discrimination, and affect social relationships. These factors combined may ultimately impact upon educational performance and family harmony13 Hypoglycaemic unawareness Up to 25% of those with type 1 diabetes experience hypoglycaemic unawareness.9 Both children and the elderly are at risk for not being able to recognise and respond to their hypoglycaemic symptoms3,17

Type 2 Diabetes
About Type 2 Diabetes
Type 2 diabetes, previously called non-insulin-dependent diabetes mellitus (NIDDM) or adultonset diabetes, accounts for approximately 85-95% of all diagnosed cases of diabetes... More... Type 2 diabetes, previously called non-insulin-dependent diabetes mellitus (NIDDM) or adultonset diabetes, accounts for approximately 85-95% of all diagnosed cases of diabetes.1,18 Once thought to be an adult disease, type 2 diabetes is increasingly being diagnosed in children and adolescents14,15 and is rapidly becoming a global public health issue.19 Type 2 diabetes is not a discreet entity, but is instead a heterogeneous, chronic, progressive disease characterised by insulin resistance, along with relatively impaired beta-cell function.1 While the course of the disease is variable; it usually follows a predictable course. In the early stages, individuals with type 2 diabetes have sufficient pancreatic reserves to compensate for insulin resistance and can maintain relatively normal blood glucose levels.20 However, over time, the need for insulin increases and the pancreas gradually loses its ability to produce insulin.1

Risk Factors for Type 2 Diabetes

Known risk factors for type 2 diabetes include:

Weight Increased weight contributes to the risk of diabetes. In particular, the increasing prevalence of childhood obesity has led to a rise in the incidence of type 2 diabetes among children3 Sedentary lifestyle, i.e., inactivity and lack of exercise3 Smoking3,21,22 Family history - Although no major susceptibility genes have been identified,23 around 20 genetic variants are reportedly associated with type 2 diabetes24 Race Blacks, Hispanics, American Indians, and Asian-Americans are more likely to develop type 2 diabetes25 Age The risk of developing type 2 diabetes increases with age, especially after 45 years of age, but incidence is increasing dramatically among children, adolescents, and younger adults Pre-diabetes Gestational diabetes mellitus (GDM) While GDM is an independent risk factor for type 2 diabetes, having a baby weighing more than 4.1 kilograms can also contribute to risk of developing type 2 diabetes

Preventative Measures
There is strong evidence that preventive measures have substantial positive effects throughout the course of type 2 diabetes. Primary prevention preventing or delaying the onset of type 2 diabetes involves encouraging and enabling healthy lifestyle choices including a balanced diet and moderate-intensity physical activity. The Diabetes Prevention Program, conducted at 27 sites throughout the United States and involving 3,000 overweight patients, showed that lifestyle modification can reduce the development of diabetes by up to 58% over 3 years in people with pre-diabetes.5

Challenges of Type 2 Diabetes

Some of the challenges associated with type 2 diabetes include:

The ultimate goal of diabetes therapy is to prevent complications. Most of the decisions which affect the risk of complications are made by the individuals with diabetes. Therefore, structured and tailored education for both patients and carers is crucial for adequate management of the condition3 Type 2 diabetes has a long asymptomatic phase which, although frequently undetected, is a period during which complications may be developing.3 Many people already have at least one complication at the time of diagnosis26 Rising incidence of type 2 diabetes at a younger age often makes the distinction from type 1 diabetes difficult. Treatment regimens, educational approaches, and dietary counsel will differ markedly between the two conditions and so appropriate diagnosis is crucial3 Increasing urbanisation in countries such as India and China has led to adoption of Western-style diets and sedentary patterns that have dramatically increased the number of people with type 2 diabetes18

The urgent need for early diagnosis and treatment has been intensified by the dramatic rise in diabetes prevalence, but guidelines for screening are unresolved and not welldefined27

Optimal diabetes care may be limited by the availability of healthcare resources, including trained personnel, medicines, and monitoring

Gestational Diabetes
About Gestational Diabetes
Gestational diabetes mellitus (GDM) is a glucose intolerance which is first diagnosed during pregnancy... Gestational diabetes mellitus (GDM) is a glucose intolerance which is first diagnosed during pregnancy. It appears with varying degrees of severity and can affect both the health of the mother and her unborn child.1,24 GDM can often be controlled through proper diet and regular exercise, but may also require insulin treatment. Optimal maternal glycaemic control is important to reduce complications in the child such as increased size and trauma at birth, hypoglycaemia, and jaundice.24 While GDM does not normally persist after birth, 5-10% of women with GDM are found to have type 2 diabetes following pregnancy. Furthermore, in women diagnosed with GDM the incidence of type 2 diabetes was observed to increase markedly in the first five years following delivery, reaching a plateau after 10 years.28 GDM is also associated with an increased risk to the offspring of obesity and abnormal glucose metabolism during childhood and adult life.24

Risk Factors for Gestational Diabetes

Known risk factors for gestational diabetes include:29

Family history of diabetes among first-degree relatives Race African-Americans, American Indians, Asian-Americans, Hispanic/Latino, or Pacific Islanders are more likely to develop gestational diabetes Increasing maternal age and weight Personal history of gestational diabetes Women with gestational diabetes in a previous pregnancy have a 30-50% probability of developing it in a subsequent pregnancy Having given birth to at least one baby weighing more than 4.1 kilograms Pre-diabetes

Preventative Measures
Weight loss, increased levels of physical activity, reduction in fat intake, and avoidance of cigarette smoking or other behaviours that might increase insulin resistance are likely to reduce the risk of developing type 2 diabetes among women with a history of GDM.30

Challenges of Gestational Diabetes

Some challenges associated with Gestational Diabetes include:

As with type 2 diabetes, the incidence of gestational diabetes is increasing18and the subsequent risk of developing type 2 diabetes is high18,31

Lack of sufficient guidance on diagnosis and management. In 2009, the International Diabetes Federation (IDF) issued its first-ever Global Guideline on Pregnancy and Diabetes29

Lack of consensus regarding screening guidelines, including guidance on whom should undergo oral glucose tolerance testing and whether screening is a one- or two-stage procedure.29 The American Diabetes Association (ADA) and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) currently recommend screening for all pregnant women between 24-28 weeks3,3

Other Diabetes Types

Diabetes resulting from other aetiologies, including specific genetic conditions, surgery, drugs, malnutrition, infections, and other illnesses... Diabetes resulting from other aetiologies, including specific genetic conditions, surgery, drugs, malnutrition, infections, and other illnesses may account for 1-5% of all diagnosed cases of diabetes.1

Maturity onset diabetes of the young

Maturity onset diabetes of the young (MODY), a group of disorders characterised by beta-cell dysfunction, affects an estimated 1-5% of people with diabetes in the United States and other industrialised countries.32 MODY occurs in children, adolescents, and young adults and is inherited as an autosomal dominant trait.32 Unlike type 2 diabetes, which likely affects multiple genes, each type of MODY is caused by a single gene mutation.32 The severity of MODY varies depending on the gene affected. MODY 3 causes progressive diabetes and may lead to microvascular complications. MODY 2 causes a mild diabetes that can often be treated with diet modification alone and rarely causes complications.32

Challenges in managing MODY

Some of the challenges associated with managing this disease include:

MODY is often not recognised and may be mistakenly treated as type 1 or type 2 diabetes Delays in diagnosis due to the absence of symptoms associated with mild hyperglycaemia
33

The existence of MODY variants between racial or ethnic groups, e.g., a variant called atypical diabetes mellitus that occurs in young blacks which initially presents as an acuteonset form of diabetes, but later reverts to a non-insulin requiring course similar to MODY in whites33

Other types of diabetes

Alternative forms of diabetes are cited in the wider literature and the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, in its aetiologic classification of diabetes mellitus, also refers to several other types of diabetes:34

Latent autoimmune diabetes mellitus in adults (LADA) A slowly progressive type 1 autoimmune diabetes35,36

Type 3 diabetes A neuroendocrine disorder related to Alzheimers Disease37,38 Ketosis-prone Diabetes (KPD)39 Genetic defects in beta-cell function (e.g., maternally inherited diabetes and deafness [MIDD]) Genetic defects in insulin action (e.g., type A insulin action and lipoatrophic diabetes) Disease of the exocrine pancreas Endocrinopathies (e.g., Cushings syndrome, glucagonoma, and phaeochromocytoma) Drug- or chemical-induced (e.g., glucocorticoids, beta-adrenergic agonists, and alphainterferon) Infections (e.g., congenital rubella and cytomegalovirus) Uncommon forms of immune-mediated diabetes (e.g., stiff-man syndrome and antiinsulin receptor antibodies) Other genetic syndromes associated with diabetes (e.g., Down syndrome, Klinefelter syndrome, Turner syndrome, etc.) Diabetes Insipidus (DI) This condition is very different to diabetes mellitus and significantly less prevalent. It is caused by the bodys inability to retain water through the dysregulation of anti-diuretic hormone (ADH). ADH functions to slow down the production of urine from the kidneys, however, in DI a reduced quantity of ADH or the inability of the kidney to respond to it results in the production of large quantities of dilute urine and hence loss of water4