ASSESSMENT OF INSULIN ACTION AND GLUCOSE EFFECTIVENESS IN DIABETIC AND NONDIABETIC HUMANS

Insulin concentrations in humans continuously change and typically inc rease only when glucose also increases such as with eating. In this se tting, it is not known whether the severity of hepatic and extrahepati c insulin resistance is comparable and whether the ability of glucose to regulate its own uptake and release is defective in non-insulin-dep endent diabetes mellitus (NIDDM). To address this question, NIDDM and nondiabetic subjects were studied when glucose concentrations were cla mped at either 5 mM (euglycemia) or varied so as to mimic the glucose concentrations observed in nondiabetic humans after food ingestion (hy perglycemia). Insulin was infused so as to simulate a ''nondiabetic'' postprandial profile. During euglycemia, insulin increased glucose dis posal in nondiabetic but not diabetic subjects indicating marked extra hepatic resistance. In contrast, insulin-induced suppression of glucos e release was only minimally less (P < 0.05) in diabetic than nondiabe tic subjects (-1.06+/-0.09 vs. -1.47+/-0.21 nmol.kg(-1) per 4 h). Hype rglycemia substantially enhanced disposal in both groups. Glucose effe ctiveness measured as the magnitude of enhancement of disposal (0.59+/ -0.18 vs 0.62+/-0.17 nmol.kg(-1) per 4 h) and suppression of release ( -0.36+/-0.12 vs. -0.14+/-0.12 nmol.kg(-1) per 4 h) did not differ in t he diabetic and nondiabetic subjects. In conclusion, when assessed in the presence of a physiological insulin profile, people with NIDDM dem onstrate: (a) profound extrahepatic insulin resistance, (b) modest hep atic insulin resistance, and (c) normal ability of glucose to stimulat e its own uptake and suppress its own release.