Type II diabetes: toward improved understanding and rational therapy.

Still not clearly defined is the fundamental defect or defects involved in the pathogenesis of type II noninsulin-dependent diabetes mellitus. Abnormalities in both insulin secretion and insulin action have been demonstrated, and there has been considerable debate as to which is the predominant lesion. During the 1970s, with the evolution of the concept of two major types of diabetes—type I and type II—a simplistic view developed that type I diabetes involved islet B-cell deficiency and a marked impairment in insulin secretion, while type II diabetes involved an impairment in insulin action, generally attributable to diminished insulin receptors on target cells. This view gained credence by virtue of the observations that insulin receptor concentration increased and insulin action improved in association with the use of many of the therapeutic modalities common in the treatment of type II diabetes: calorie restriction, physical training, and sulfonylurea therapy." Nevertheless, numerous studies have established that patients with type II diabetes have impaired islet B-cell function as well.' Indeed, since simple obesity is associated with impairment of insulin action and diminished insulin receptors in the absence of glucose intolerance, it would seem that impaired islet B-cell function is a universal feature of type II diabetes. Thus, type II diabetes is characterized by defects both in islet B-cell function and in insulin action.