Diabetes mellitus type 2 pathophysiology


 * Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [mailto:psingh@perfuse.org];

Pathophysiology
Insulin resistance means that body cells do not respond appropriately when insulin is present.

Other important contributing factors:
 * increased hepatic glucose production (e.g., from glycogen degradation), especially at inappropriate times
 * decreased insulin-mediated glucose transport in (primarily) muscle and adipose tissues (receptor and post-receptor defects)
 * impaired beta-cell function—loss of early phase of insulin release in response to hyperglycemic stimuli
 * Cancer survivors who received allogenic Hematopoeitic Cell Transplantation (HCT) are 3.65 times more likely to report type 2 diabetes than their siblings. Total body irradiation (TBI) is also associated with a higher risk of developing diabetes.

This is a more complex problem than type 1, but is sometimes easier to treat, especially in the initial years when insulin is often still being produced internally. Type 2 may go unnoticed for years in a patient before diagnosis, since the symptoms are typically milder (no ketoacidosis) and can be sporadic. However, severe complications can result from unnoticed type 2 diabetes, including renal failure, blindness, wounds that fail to heal, and coronary artery disease. The onset of the disease is most common in middle age and later life.

Diabetes mellitus type 2 is presently of unknown etiology (i.e., origin). Diabetes mellitus with a known etiology, such as secondary to other diseases, known gene defects, trauma or surgery, or the effects of drugs, is more appropriately called secondary diabetes mellitus. Examples include diabetes mellitus caused by hemochromatosis, pancreatic insufficiency, or certain types of medications (e.g. long-term steroid use).

About 90–95% of all North American cases of diabetes are type 2, and about 20% of the population over the age of 65 has diabetes mellitus type 2. The fraction of type 2 diabetics in other parts of the world varies substantially, almost certainly for environmental and lifestyle reasons, though these are not known in detail. Diabetes affects over 150 million people worldwide with this number expected to double by 2025. There is also a strong inheritable genetic connection in type 2 diabetes: having relatives (especially first degree) with type 2 is a considerable risk factor for developing type 2 diabetes. In addition there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe form of diabetes,. About 55 percent of type 2 are obese —chronic obesity leads to increased insulin resistance that can develop into diabetes, most likely because adipose tissue is a (recently identified) source of chemical signals (hormones and cytokines). Other research shows that type 2 diabetes causes obesity.

Diabetes mellitus type 2 is often associated with obesity and hypertension and elevated cholesterol (combined hyperlipidemia), and with the condition Metabolic syndrome (also known as Syndrome X, Reavan's syndrome, or CHAOS). It is also associated with acromegaly, Cushing's syndrome and a number of otherendocrinological disorders. Additional factors found to increase risk of type 2 diabetes include aging, high-fat diets and a less active lifestyle.