Pathogenesis of non-insulin-dependent (type II) diabetes mellitus (NIDDM) - genetic predisposition and metabolic abnormalities.

Abstract

Non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diabetes, is characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with microvascular, macrovascular, and neuropathic complications. NIDDM is a complex disease with many causes. Both genetic and environmental factors play important roles in the pathogenesis of NIDDM. Cumulative evidence on the high prevalence of NIDDM in certain ethnic groups, the high concordance rate for the disease in monozygotic twins, familial aggregation, and familial transmission patterns suggests that the genetic component plays an important etiological role in the development of NIDDM. In genetically predisposed individuals, there is a slow progression from a normal state to hyperglycemia, largely due to a combination of insulin resistance and defects in insulin secretion. Although numerous candidate genes responsible for insulin resistance and for the defects in insulin secretion have been reported, no specific gene(s) accounting for the majority of cases of the common type of NIDDM has been identified. Considerable evidence indicates that environmental and other factors, including diet, stress, physical activity, obesity and aging, also play an important role in the development of the disease. In conclusion, the pathogenic process of NIDDM depends on a complex interaction between genetic and environmental factors.