Insulin resistance: from benign to type 2 diabetes mellitus

Type 2 diabetes has become the most frequently encountered metabolic disorder in the world, currently affecting 5% to 10% of most populations, and the incidence continues to grow among developing nations. Two fundamental abnormalities are involved in the pathogenesis of type 2 diabetes: Resistance to the biologic activities of insulin in glucose and lipid metabolism and inadequate insulin secretion from the pancreatic B cells. In genetically predisposed individuals, type 2 diabetes is pathogenically linked with progressive obesity, especially adiposity that is visceral or ectopic in distribution. While microvascular complications (retinopathy, nephropathy, neuropathy) continue to plague patients with longstanding type 2 diabetes, cardiovascular disease has assumed particular importance, accounting for more than 80% of adverse outcomes among patients. Since the aggressive management of diabetes and its complications poses a considerable challenge, large trials to prevent the progression to overt diabetes in persons at high risk have recently demonstrated that lifestyle modification and pharmaceutical therapy can be successful approaches. A better understanding of the complex relationship between obesity and both the development of type 2 diabetes and its cardiovascular complications may provide additional treatment targets in the future to prevent the devastating chronic morbidity of this disorder.