Pathogenesis of impaired glucose tolerance and type II diabetes mellitus--current status

Abstract

The insulin response to glucose taken orally is increased in patients with impaired glucose tolerance (IGT) but decreased in those with type II diabetes mellitus. The insulin response to meals, however, is normal in patients with type II diabetes, although the glucose concentrations are obviously elevated. The acute insulin response to intravenously administered glucose is absent in cases of both IGT and type II diabetes when the fasting plasma glucose level exceeds 115 mg per dl. On the other hand, the response to other intravenously given secretagogues is either normal or nearly so. The absent acute insulin response to intravenously administered glucose can be restored by alpha-adrenergic blockade, prostaglandin synthesis inhibition, dopaminergic blockade and euglycemia. Insulin antagonism characterizes patients with both IGT and type II diabetes. Those with IGT and mild diabetes mellitus (untreated fasting plasma glucose concentrations < 180 mg per dI) have a receptor defect probably due to down regulation. Diabetic patients with more severe type II diabetes show a postreceptor defect. The relation (if any) between receptor and postreceptor defects is unclear.