Diabetes is a metabolic disease characterized by hyperglycemia (raised blood glucose) resulting from defects in insulin secretion, insulin action, or both [1]. Insulin, produced by the beta cells of the pancreatic islets of Langerhans, is the main hormone regulating blood glucose levels, and is released in response to rising blood glucose following eating or drinking. Insulin has wide-ranging metabolic effects, which include the stimulation of glucose uptake into skeletal muscle and liver, and key roles in lipid and protein metabolism.

The diagnosis of diabetes has traditionally been based on blood glucose levels, but in the last few years glycated haemoglobin (HbA1c) has been accepted as an alternative. The ‘gold standard’ diagnostic test or reference method has been taken to be the oral glucose tolerance test (OGTT). In brief, an OGTT involves the measurement of fasting glucose, followed by a drink containing a fixed quantity of glucose, and the measurement of blood glucose 2 hours after that drink. Undertaking an OGTT is time consuming and relatively expensive (compared to fasting glucose alone). Largely for these pragmatic reasons, the ADA recommends using fasting glucose alone as the main diagnostic test. Unfortunately, however, around one-third of individuals who have diabetes will have an abnormal result after an OGTT but fasting glucose below the diabetes threshold [2]. 

In other words, using fasting glucose alone misses about one-third of individuals with diabetes. Similarly, with fasting glucose, it is impossible to identify those who fall into the category of intermediate hyperglycaemia based on the post-glucose challenge result (impaired glucose tolerance (IGT)), and much of the evidence on preventing type 2 diabetes is in individuals with IGT. It is for all these reasons that the WHO continues to recommend using an OGTT as the main diagnostic test.    

Incidence, Prevalence and Trends

The International Diabetes Federation (IDF) produces global estimates of the number of people with diabetes and how their numbers are expected to increase in the future. These estimates are mainly based on studies in which   blood glucose   was tested and thus include people with diagnosed and undiagnosed diabetes. This is important because in many populations more than half the people with diabetes, sometimes as many as 80 or 90 per cent, have not been diagnosed. The prevalence of diabetes rises steeply with age, but tends to plateau or even fall slightly in those aged 70 years and above [3].

Risk Factors and Social Determinants

There are strong genetic and environmental (in its broadest sense) influences on the risk of both type 1 and type 2 diabetes, and it is the interaction between the two that results in the onset of the disease. The environmental influences on the risk of type 2 diabetes include low levels of physical activity, diets high in saturated fat, salt, and refined carbohydrate, and low in whole grains, fresh fruit, vegetables, and fibre, calorie excess and obesity, and tobacco exposure. The environmental influences on type 1 diabetes remain frustratingly elusive.

Risk Factors for Type 1 Diabetes

Familial and Genetic: The lifetime risk of type 1 diabetes is roughly 6 per cent if a first-degree relative has the condition, such as a sibling, compared to roughly 0.4 per cent (depending on the population) if a first-degree relative is not affected. If a monozygotic twin has type 1 diabetes, the lifetime risk in the other twin is around 50 percent [4].

Environmental Factors

The importance of environmental factors is indicated by the changing incidence of type 1 diabetes (described earlier) at a rate that is far too rapid to be due to changes in the gene pool [5].

Risk Factors for Type 2 Diabetes

Unmodifiable Risk Factors for Type 2 Diabetes

Age and sex: The risk of type 2 diabetes increases steeply with age. Most UK-based studies of previously diagnosed diabetes have found a slightly higher prevalence in men, whereas studies in which glucose is measured either find no sex difference or a slightly higher prevalence in women.

Familial and Genetic

The strong familial clustering of type 2 diabetes, suggestive of important genetic influences, has been known for many years [6]. For example, the presence of type 2 diabetes in a parent or sibling approximately doubles the risk of type 2 diabetes. However, identifying genetic markers for type 2 diabetes has proved difficult, and the markers identified to date account for only a few per cent of the genetic risk [7].

The reasons for the current lack of success in accounting for the heritability of type 2 diabetes and other chronic diseases are debated. They are likely in part to reflect the(unmeasured) contribution of epigenetic changes to diabetes risk [8].

Previous Gestational Diabetes

Women with gestational diabetes tend to be older, more overweight, have a family history of diabetes, and be from an ethnic group with high prevalence of diabetes. Following delivery, glucose levels return to normal in around 90 per cent of women, but over the next 10 years, as many as 70 per cent go on to develop diabetes [9].

Ethnicity

As described previously, there are marked differences in the prevalence of type 2 diabetes by ethnic group. It remains far from clear what underlies these differences, how much is related to differences in environment (including behaviours), and how much to differences in genetic susceptibility [10].

Modifiable Risk Factors for Type 2 Diabetes

Obesity, Physical Inactivity, Aspects of Diet, and Alcohol: The relationship between overweight and obesity and the risk of type 2 diabetes is continuous, very strong, and is apparent below conventional cut-points for overweight. There is good evidence that physical activity lowers the risk of type 2 diabetes independently of obesity level. Regular moderate or vigorous activity has been associated with a 30–50 per cent reduction in the risk of developing type 2 diabetes. There is also evidence that the composition of the diet, over and above its calorific value, influences the risk of type 2 diabetes.

Increased risk has been associated with diets low in fiber and high in saturated fat [11], and conversely intervention studies support the hypothesis that high-fiber, low-saturated-fat diets can help to prevent diabetes. 

Smoking

Smoking is associated with a dose-dependent increased risk of type 2 diabetes, with former, light, and heavy smokers having a risk of incident type 2 diabetes that is roughly 20, 30, and 60 per cent higher respectively than in those who have never smoked.

Diabetes-Related Complications

Diabetes affects multiple organ systems, and complications typically are divided into those affecting large arteries (macrovascular) including those supplying the heart, brain, and lower limbs, and those affecting small vessels (microvascular), including those of the kidney and eye and those supplying the peripheral nervous system. In addition, diabetes is associated with depression, and with liver dysfunction. As noted in later subsections there are some differences in the rate of complications by ethnic group, particularly for coronary heart disease, end-stage renal disease, and lower extremity amputation. The relative contributions to these ethnic group differences of differential healthcare access, behaviors and genetic susceptibility remains incompletely understood [12].

Cardiovascular Disease

The risk of cardiovascular disease in people with diabetes is two- to fourfold higher than in people without diabetes [13] and this accounts for much of the increased mortality associated with diabetes [14]. In most populations, well over 50 per cent of deaths in people with diabetes are from cardiovascular disease. In the United States, people with diabetes of African, Asian (Chinese and Japanese), and Hispanic origin have substantially lower rates of myocardial infarction than those of European origin, and those of the latter two groups lower rates of stroke. Similar findings exist in for people of African origin the United Kingdom [15].

People with diabetes of South Asian (Indian Asian) origin are at similar or higher risk of cardiovascular disease than those of European origin [16]. These differences are not explained by differences in conventional risk factors.

Diabetic Eye Disease

In developed countries, diabetes is the leading cause of blindness in people aged over 25 years [17].

Twenty years after diagnosis, virtually 100 per cent of people with type 1 diabetes have diabetic retinopathy [18] and when blood pressure and blood glucose control are poor, it is estimated that 75 per cent will develop proliferative retinopathy, the most severe form. In type 2 diabetes, between 40 and 60 per cent are expected to develop retinopathy during their lifetime, with around 10 per cent developing proliferative retinopathy. Diabetes also increases the risk of cataracts and open-angle glaucoma.

Diabetic Renal Disease

Diabetes is the leading cause of renal failure in developed countries, responsible for 40–50 per cent of all new patients requiring dialysis in North America, and 15–33 per cent in Europe and

Australia [19] In cross-sectional surveys in Europe, around one in ten people with type 1 diabetes, and one in seven with type 2 diabetes, have evidence of overt nephropathy. Approximately, 30 per cent of people with diabetes with overt nephropathy will progress to end-stage renal failure. There are marked differences by ethnic group in the risk of end-stage renal disease, with people of African and Asian origin in particular being at greater risk compared to those of European origin [20]. A high risk of diabetic renal disease has also been described from studies within Asia [21].

Neuropathy and diabetic foot problems

The nerve damage associated with diabetes can affect both peripheral and autonomic nerves. Diabetic foot problems are a result of peripheral neuropathy or peripheral vascular disease or a combination of the two [22]. In cross-sectional studies, peripheral neuropathy is found in one in five to more than a third of people with diabetes. During their lifetime, roughly 15 per cent of people with diabetes develop a foot ulcer and of these 5–15 per cent go on to amputation. In developed countries, diabetes is the single most important cause of non-traumatic lower limb amputation, accounting for 40–60 per cent of all amputations, and people with diabetes have a 15-fold risk of amputation compared to people without diabetes.

Differences exist in the risk of lower extremity amputation by ethnic group, with, for example, people of Asian origin in the United States and United Kingdom having a markedly lower risk than the European origin population.

Erectile Dysfunction

Diabetes increases the risk of erectile dysfunction in men. A large US cohort study [23] found that type 1 diabetes increased the risk threefold, and type 2 diabetes increased the risk by a third. The same study found that the prevalence of erectile dysfunction in men with diabetes was around 50 per cent.

Other Co-Morbidities

Depressive illness is up to twice as common in people with diabetes than those without [24]. Depressive symptoms are also a risk factor for type 2 diabetes, associated with roughly a 50 per cent increase in risk [25].

Depression in people with diabetes is associated with more complications and poorer self-care [26]. Non-alcoholic fatty liver disease is found in the majority of people with type 2 diabetes [27].

It is also a risk factor for its development, with some arguing that it is a key part of the pathogenesis [28].  In people with diabetes, it is strongly associated with the risk of complications, including macrovascular disease and, of course, chronic liver disease [29]. Finally, there is consistent evidence that diabetes is associated with a 30–40 per cent increased risk of several cancers including of the breast, endometrium, liver, and colon.

1. American Diabetes Association. "Diagnosis and classification of diabetes mellitus." Diabetes Care, vol. 27, 2004, pp. 5S–10.

2. Decode Study Group. "Is fasting glucose sufficient to define diabetes? Epidemiological data from 20 European studies." Diabetologia, vol. 42, 1999, pp. 647–54.

3. Whiting, D.R. et al "IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030." Diabetes Research and Clinical Practice, vol. 94, 2011, pp. 311–21.

4. Hirschhorn, J.N. "Genetic epidemiology of type 1 diabetes." Pediatric Diabetes, vol. 4, 2003, pp. 87–100.

5. Vehik, K. and Dabelea, D. "The changing epidemiology of type 1 diabetes: why is it going through the roof?" Diabetes/Metabolism Research and Reviews, vol. 27, 2011, pp. 3–13.

6. Zimmet, P.Z. "Kelly West lecture 1991. Challenges in diabetes epidemiology— from West to the rest." Diabetes Care, vol. 15, 1992, pp. 232–52.

7. Permutt, M.A. et al "Genetic epidemiology of diabetes." Journal of Clinical Investigation, vol. 115, 2005, pp. 1431–9.

8. Drong, A.W. et al "The genetic and epigenetic basis of type 2 diabetes and obesity." Clinical Pharmacology & Therapeutics, vol. 92, 2012, pp. 707–15.

9. Buchanan, T.A. and Xiang, A.H. "Gestational diabetes mellitus." Journal of Clinical Investigation, vol. 115, 2005, pp. 485–91.

10. Oldroyd, J. et al "Diabetes and ethnic minorities." Postgraduate Medical Journal, vol. 81, 2005, pp. 486–90.

11. Parillo, M. and Riccardi, G. "Diet composition and the risk of type 2 diabetes: epidemiological and clinical evidence." British Journal of Nutrition, vol. 92, 2004, pp. 7–19.

12. Karter, A.J. et al "Ethnic disparities in diabetic complications in an insured population." Journal of the American Medical Association, vol. 287, 2002, pp. 2519–27.

13. Stamler, J. et al "Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the multiple risk factor intervention trial." Diabetes Care, vol. 16, 1993, pp. 434–44.

14. Roglic, G. and Unwin, N. "Mortality attributable to diabetes: estimates for the year 2010." Diabetes Research and Clinical Practice, vol. 87, 2010, pp. 15–19.

15. Davis, T.M. "Ethnic diversity in type 2 diabetes." Diabetic Medicine, vol. 25, 2008, pp. 52–6.

16. Gholap, N. et al "Type 2 diabetes and cardiovascular disease in South Asians." Primary Care Diabetes, vol. 5, 2011, pp. 45–56.

17. Klein, R. and Klein, B.E. "Vision disorders in diabetes." In National Diabetes Data Group. Diabetes in America (2nd ed.), 1995, pp. 293–338.

18. Roy, M.S. et al "The prevalence of diabetic retinopathy among adult type 1 diabetic persons in the United States." Archives of Ophthalmology, vol. 122, 2004, pp. 546–51.

19. Atkins, R.C. "The epidemiology of chronic kidney disease." Kidney International, vol. 67, 2005, pp. S14–18.

20. Lanting, L.C. et al "Ethnic differences in mortality, end-stage complications, and quality of care among diabetic patients: a review." Diabetes Care, vol. 28, 2005, pp. 2280–8.

21. Chan, J.C. et al "Diabetes in Asia: epidemiology, risk factors, and pathophysiology." Journal of the American Medical Association, vol. 301, 2009, pp. 2129–40.

22. Edmonds, M. et al "Report of the diabetic foot and amputation group." Diabetic Medicine, vol. 13, 1996, pp. S27–S42.

23. Bacon, C.G. et al "Association of type and duration of diabetes with erectile dysfunction in a large cohort of men." Diabetes Care, vol. 25, 2002, pp. 1458–63.

24. Egede, L.E. and Ellis, C. "Diabetes and depression: global perspectives." Diabetes Research and Clinical Practice, vol. 87, 2010, pp. 302–12.

25. Demakakos, P. et al "Depressive symptoms and risk of type 2 diabetes in a national sample of middle-aged and older adults." Diabetes Care, vol. 33, 2010, pp. 792–7.

26. Lin, E.H.B. et al "Relationship of depression and diabetes self-care, medication adherence, and preventive care." Diabetes Care, vol. 27, 2004, pp. 2154–60.

27. Targher, G. and Byrne, C.D. "Clinical review: nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications." Journal of Clinical Endocrinology and Metabolism, vol. 98, 2013, pp. 483–95.

28. Taylor, R. "Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause." Diabetologia, vol. 51, 2008, pp. 1781–9.