The importance of the beta-cell in the pathogenesis of type 2 diabetes mellitus.

beta-cell dysfunction and insulin resistance are two central, interrelated defects in the pathophysiology of type 2 diabetes. By the time a patient's hyperglycemia is recognized, disruption of the normal relationship between beta-cell function and insulin sensitivity is already well established. The pathophysiology and progression of defects in glucose metabolism from normal glucose tolerance to impaired glucose tolerance to frank type 2 diabetes have been studied extensively. Insulin sensitivity has wide intersubject variability, and many individuals at risk for type 2 diabetes are insulin resistant. beta-cell changes in patients with type 2 diabetes include defects in insulin secretion, proinsulin conversion to insulin, and amyloid deposition in the islet. Studies in several ethnic groups have established that the progression from normal glucose tolerance to frank type 2 diabetes results from a gradual deterioration in beta-cell function in the presence of insulin resistance. Furthermore, the recently completed landmark United Kingdom Prospective Diabetes Study demonstrated that type 2 diabetes is a progressive disease and that this progression is due to declining beta-cell function.