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

Non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diab etes, is characterized by abnormal glucose homeostasis, resulting in hyperg lycemia, and is associated with microvascular, macrovascular, and neuropath ic complications. NIDDM is a complex disease with many causes. Both genetic and environmental factors play important roles in the pathogenesis of NIDD M. Cumulative evidence on the high prevalence of NIDDM in certain ethnic gr oups, the high concordance rate for the disease in monozygotic twins, famil ial aggregation: and familial transmission patterns suggests that the genet ic component plays an important etiological role in the development of NIDD M. In genetically predisposed individuals, then is a slow progression from a normal state to hyperglycemia, largely due to a combination of insulin re sistance and defects in insulin secretion. Although numerous candidate gene s responsible for insulin resistance and for the defects in insulin secreti on have been reported, no specific gene(s) accounting for the majority of c ases of the common type of NIDDM has been identified. Considerable evidence indicates that environmental and other factors, including diet, stress, ph ysical activity, obesity and aging, also play an important role in the deve lopment of the disease. In conclusion, the pathogenic process of NIDDM depe nds on a complex interaction between genetic and environmental factors. (C) 1999 Published by Elsevier Science B.V.