OVERNIGHT NORMALIZATION OF GLUCOSE-CONCENTRATIONS IMPROVES HEPATIC BUT NOT EXTRAHEPATIC INSULIN ACTION IN SUBJECTS WITH TYPE-2 DIABETES-MELLITUS

Subjects with poorly controlled type 2 diabetes are both hyperglycemic and insulin resistant. To determine whether short term restoration of normoglycemia improves insulin action, hyperinsulinemic (similar to 3 00 pmol/L) euglycemic clamps were performed in diabetic subjects after either overnight infusion of saline or overnight infusion of insulin in amounts sufficient to maintain euglycemia throughout the night. Fas ting glucose concentrations (5.2 +/- 0.2 vs. 11.9 +/- 1.4 mmol/L; P < 0.01) and rates of endogenous glucose production (13.0 +/- 1.I us. 18. 6 +/- 1.6 mu mol/kg.min; P < 0.05) were both lower after overnight ins ulin than overnight saline. Insulin-induced stimulation of glucose upt ake (to 34.9 +/- 6.8 vs. 28.8 +/- 3.4 mu mol/kg.min; P = 0.2) and inhi bition of free fatty acids (to 0.13 +/- 0.03 vs. 0.12 +/- 0.04 mmol/L; P = 0.6) did not differ after overnight saline and overnight insulin. In contrast, endogenous glucose production during the final hour of t he hyperinsulinemic clamps (i.e. when glucose concentrations were the same) remained higher (P = 0.05) after overnight saline than after ove rnight insulin (5.5 +/- 1.5 us. 0.02 +/- 1.4 mu mol/kg min). Thus, acu te restoration of euglycemia by means of an overnight insulin infusion improves hepatic (and perhaps renal) but not extrahepatic insulin act ion.