Plasma Insulin Responses to Glucose and Tolbutamide of Normal Weight and Obese Diabetic and Nondiabetic Subjects

Abstract

Plasma insulin responses to oral glucose (100 g) and intravenous tolbutamide (1.0 g) before and after dexamethasone were determined in normal, obese nondlabetic, normal-weight diabetic and obese diabetic subjects. Fasting plasma insulin levels were significantly higher in obese nondiabetic and obese diabetic subjects than in normal-weight nondiabetic and diabetic individuals. Total plasma insulin response to oral glucose in obese nondlabetics was threefold greater, in obese diabetics 2.2-fold greater, and in normal-weight diabetics 1.7-fold greater than that observed in normal individuals. When the plasma insulin responses of obese diabetic and nondlabetic subjects were measured at comparable blood sugar levels, insulin secretion was demonstrated to be significantly impaired in the diabetic group. The initial plasma isulin response (i.e., thirty-minute level) to glucose of diabetic subjects is markedly impaired when compared to normal-weight and obese nondiabetic individuals. Total plasma insulin response to intravenous tolbutamide was fourfold greater in obese nondiabetic and obese diabetic subjects than in normal-weight nondiabetic and diabetic individuals. Following dexamethasone (2 m q.i.d. x 2), plasma insulin response to intravenous tolbutamide was increased fivefold in normal subjects, threefold in obese nondlabetics, 1.6-fold in obese diabetics and twofold in nonobese diabetics. The results of these studies indicate that obesity is associated with hypersecretory insulin response to both tolbutamide and glucose. The presence of overt diabetes mellitus indicates an impairment in isulin response in both obese and nonobese individuals when compared to their appropriate nondiabetic controls. Dexamethasone provokes a marked compensatory insulin response in nondiabetics and makes more apparent the impaired secretory capacity of diabetic subjects. Maturity-onset diabetes in nonobese individuals appears to be a consequence primarily of insulin deficiency. In obese diabetic individuals, however, even though secretory capacity may be significantly greater than observed in nonobese diabetics, impaired carbohydrate tolerance develops because of insulin antagonism associated with obesity perse.