ASSESSMENT OF INSULIN ACTION IN NIDDM IN THE PRESENCE OF DYNAMIC CHANGES IN INSULIN AND GLUCOSE-CONCENTRATION

Both glucose and insulin are important regulators of glucose uptake an d hepatic glucose release. Because insulin concentrations rarely if ev er increase under daily living conditions, unless glucose concentratio ns also increase, we sought to determine whether hepatic and extrahepa tic responses to changes in insulin and glucose concentration are impa ired in patients with non-insulin-dependent diabetes mellitus (NIDDM). To address this question, glucose metabolism was measured in diabetic and nondiabetic subjects. A computer-driven infusion system was used to produce a nondiabetic postprandial insulin profile in both groups w hile sufficient exogenous glucose was Infused to mimic nondiabetic pos tprandial glucose concentrations. Although NIDDM was associated with g reater (P < 0.05) hepatic glucose release both before and during the p randial insulin infusion, suppression did not differ in the diabetic a nd nondiabetic subjects (-1.06 +/- 0.20 vs. -0.86 +/- 0.15 mmol/kg eve ry 4 h). In contrast, stimulation of both glucose disappearance (0.77 +/- 0.27 vs. 1.68 +/- 0.27 mmol/kg every 4 h) and forearm glucose upta ke (187 +/- 81 vs. 550 +/- 149 mu mol/dl every 4 h) was lower (P < 0.0 5) in diabetic than in nondiabetic subjects. Thus, despite increased b asal rates of glucose production, obese individuals with NIDDM had dec reased stimulation of glucose disappearance but normal suppression of hepatic glucose release in response to nondiabetic prandial glucose an d insulin concentrations. These data indicate that the increase in glu cose that occurs with carbohydrate ingestion is likely to compensate f or hepatic but not extrahepatic insulin resistance.