Clinical features of insulin resistance and beta cell dysfunction and the relationship to type 2 diabetes

Type 2 diabetes mellitus is a heterogeneous disorder characterized by varyi ng degrees of impaired insulin secretion and insulin resistance. The metabo lic manifestations of insulin resistance include (1) reduced insulin-stimul ated glucose uptake, (2) reduced insulin-suppression of endogenous glucose production, and (3) reduced antilipolysis. All of these mechanisms contribu te to the hyperglycemia of T2DM, both post-absorptively and postprandially. In addition, insulin resistance is involved in decreased insulin-induced v asodilation, dyslipidemia, and platelet hyperaggregability. The pathogenesi s of T2DM involves a combination of genetic and environmental factors. Mono genic causes account for only a minority of insulin resistance and beta cel l dysfunction. Among environmental factors the most important are obesity, reduced physical activity, and age. Obesity-associated insulin resistance i s thought to be mediated mainly by FFAs whose clearance is reduced in subje cts with T2DM. A number of clinical tests have been developed to assess ins ulin sensitivity and beta cell function in vivo. The euglycemic hyperinsuli nemic clamp and the hyperglycemic clamp, respectively, represent the gold s tandard procedures. Recently, indices calculated from parameters of the OGT T have been proposed as surrogates for assessing both insulin sensitivity a nd beta cell function in clinical situations and epidemiologic studies.