Epidemiology and Disease Pathology of Type 2 Diabetes

Type 2 diabetes, or non-insulin-dependent diabetes as it was formerly known, is characterized by insulin resistance; that is, although a sufferer may produce enough insulin, body cells are resistant to its effects. The most common type of diabetes, it is most frequently found in people over the age of 40, although the incidence among youth is rising dramatically.

Epidemiology

Prevalence

In 2002, nearly 18.2 million people in the US were believed to have diabetes (~6.3% of the population). Of this population, ~13 million were diagnosed and ~5.2 million undiagnosed. Furthermore, its prevalence is increasing. It has been predicted that there will be at least 350 million people in the world with type 2 diabetes by the year 2030.[1] Moreover, despite generally being considered as a disease of adulthood, recent reports indicate that type 2 diabetes is becoming more common in children and adolescents.[2,5]

The risk of type 2 diabetes varies among population groups. A study undertaken in 2000 showed that African American men and women had, respectively, 1½ and 2 times the risk of whites of developing type 2 diabetes. The Pima tribe in Arizona has an incidence of type 2 diabetes that is 19 times higher than that of the white population. Other Native American tribes in North America are also at high risk for type 2 diabetes. The rate of type 2 diabetes is also very high among Mexican Americans, approximately double that of whites.[6]

The cost of type 2 diabetes

Type 2 diabetes represents a significant economic burden. In 2002, the total cost of diabetes in the US was nearly US $132 billion in medical expenditures and lost productivity.[1] The US is not alone in shouldering high costs: type 2 diabetes costs Australia AUS $3 billion a year.[7] In Ireland type 2 diabetes now accounts for 6% of the country's annual health care budget, with almost half of this money being spent on hospitalization costs.[8]

Natural history

The development of type 2 diabetes starts with a fully compensated insulin-resistant state, which then progresses to imaired glucose tolerance (IGT) and then to full-blown type 2 diabetes(Figure 1).

            Three metabolic defects characterize type 2 diabetes. These are insulin resistance, β cell dysfunction and increased hepatic glucose production (HGP). Insulin resistance is the primary and earliest defect. The β cells are at first able to compensate by secreting supraphysiological amounts of insulin. Over time, however, the β cells begin to fail and as relative insulin deficiency occurs, fasting hyperglycemia and full-blown type 2 diabetes develop. In addition, as insulin levels fall, the inhibitory effect of insulin on HGP decreases and fasting hyperglycemia is exacerbated. Further progression of the disease is marked by insulin deficiency. Other factors such as obesity, aging, and physical inactivity also affect the natural history of diabetes.[9]

Genetic factors

Although impairment of β-cell function and an abnormal response to insulin are involved in type 2 diabetes, genetic factors also play an important role. For example, a defective fatty acid-binding protein 2 (FABP2) gene may result in higher levels of triglycerides, which may be critical in the link between obesity and insulin resistance in some people with type 2 diabetes. In addition, defects in genes that reduce the activity of β-3-adrenergic receptor, which is found in visceral fat cells, have been found. This defect results in a slowdown in metabolism and an increase in obesity and has a very high incidence in type 2 diabetes and obesity. Additional gene defects considered to be significant include those affecting the FABP2 gene and the lipoprotein lipase. Variations in a gene that regulates the protein calpain-10 have been shown to affect insulin secretion and action and may play a role in type 2 diabetes.[5]

Obesity and its role in type 2 diabetes

Obesity and type 2 diabetes are closely linked; many patients with type 2 diabetes are obese. Even if a patient is not obese as such, type 2 diabetes patients generally have an increased amount of visceral fat. Obesity is thought to exacerbate insulin resistance, and over the last few years it has been suggested that cytokines could play a role in the pathophysiology of obesity and insulin resistance. A recent study showed a positive correlation between circulating interleukin-6 (IL-6) levels and obesity and insulin resistance, suggesting that IL-6 could be involved in insulin resistance(Figure 2).[10]

Related conditions

Diabetic neuropathy

Diabetic neuropathy is a complication of high blood glucose in people who have diabetes. Some evidence of neuropathy is present in 60% of all individuals with the disease.[11]

Foot ulcers

When combined with poor circulation, neuropathy can result in diabetic foot ulcers and leg infections. Diabetic foot ulcers are expected to affect 2.4 million people, or 15% of the 16 million people with diabetes.[12]

Heart disease and stroke

Type 2 diabetes is associated with clustering of coronary risk factors and 60% to 80% of patients have hypertension. Furthermore, people with diabetes are 2 to 4 times more likely than people who do not have diabetes to die from heart and blood vessel diseases.[13,14,15]

Kidney disease

Diabetes accounts for 43% of new cases of end-stage renal disease (ESRD). The risk of ESRD is 12 times as high in people with type 1 diabetes as in those with type 2 diabetes; 10% to 21% of all people with diabetes have nephropathy.[1,16,17]

Blindness

Diabetes is associated with damage to the small blood vessels in the retina leading to vision loss. After 15 years of the disease, 2% of people become blind and about 10% develop severe visual disturbances; people with diabetes are 60% more likely to develop cataracts and 40% more likely to suffer from glaucoma than people without diabetes.[18]

References

1. World Health Organization. Available at: http://www.who.int/diabetes/publications/en/screening_mnc03.pdf. Accessed June 2006.
2. Rosenbloom AL et al. Emerging epidemic of type 2 diabetes in youth. Diabetes Care. 1999;22:345-354.
3. Dabelea D et al. Increasing prevalence of type 2 diabetes in American Indian children. Diabetologia. 1998;41:904-910.
4. Kitagawa T, et al. Increased incidence of non-insulin dependent diabetes mellitus among Japanese school children correlates with an increased intake of animal protein and fat. Clin Paediatr. 1998;37:111-115.
5. Reuters Health. Diabetes: Type 2. Available at: http://www.reutershealth.com/wellconnected/doc60.html. Accessed April 2004.
6. UC Davis Health System. Diabetes Facts. Available at: http://www.ucdmc.ucdavis.edu/matrix/vol7_no5_sep00/html/diabetes1.html. Accessed June 2006.
7. The Australian. Beating diabetes. Available at: http://www.theaustralian.news.com.au/story/0,20867,19191971-23289,00.html. Accessed June 2006.
8. Irish Health. Huge cost of type 2 diabetes highlighted. Available at:
   (http://www.irishhealth.com/?level=4&id=4858&var=print). Accessed April 2004.
9. Diabetes Forum. Prevention of type 2 diabetes with pharmacological agents. Available at: http://www.diabetesforum.net/cgi-bin/display_engine.pl?category_id=15. Accessed April 2004.
10. Bastard JP. Insulin resistance and adipose tissue gene expression in humans. Ann Biol Clin. 2004;62:25-31.
11. Alder AL, Boyko EJ, Ahroni JH, et al. Risk factors for diabetic peripheral sensory neuropathy. Diabetes Care. 1997;20:1162-1167.
12. American Podiatric Medical Association. Facts on diabetes and the foot. Available at: http://www.apma.org/faqsdiab.html. Accessed April 2004.
13. Cruickshank JM. Beta-blockers and diabetes: the bad guys come good. Cardiovasc Drugs Ther. 2002; 16:457-470.
14. Aspirin therapy in diabetes (Clinical Practice Recommendations 2002). Diabetes Care. 2002;25(suppl 1):S78-S79.
15. American Diabetes Association. Diabetes, heart disease and stroke. Available at: http://www.diabetes.org/type-2-diabetes/well-being/heart-disease-and-stroke.jsp. Accessed April 2004.
16. Diabetic Help. Diabetes and kidney disease. Available at: http://www.diabetic-help.com/diabetes_and_kidney_disease.htm. Accessed April 2004.
17. Lawrence J, Robinson A. Screening for diabetes in general practice. Prev Cardiol. 2003;6:78-84.
18. American Diabetes Association. Eye complications. Available at: http://www.diabetes.org/type-2-diabetes/eye-complications.jsp. Accessed April 2004.