Glucose and lipid metabolism in non-insulin-dependent diabetes. Effect of metformin

Abstract

Basal and insulin-mediated glucose and free-fatty acid (FFA) metabolism was evaluated in 6 non-insulin-dependent diabetic patients (NIDDM) previously treated by diet, before and after 4 week metformin treatment (850 mg twice/day). On both occasions, an euglycemic stepwise insulin (20 and 40 mU/m2/min) clamp was performed along with primed-continuous infusion of 3-3H-glucose and 1-14C-palmitate and indirect calorimetry monitoring. FFA oxidation rate was measured from the rate of appearance of 14CO2. After metformin therapy, fasting plasma glucose, FFA, triglyceride, total cholesterol concentrations and HbA1c were all lowered (p less than 0.05-0.01) in the absence of any change in plasma insulin levels. Plasma FFA turnover rate (5.3 +/- 0.5 vs 3.9 +/- 0.8 mumol/kg/min; p less than 0.05) and FFA oxidation (0.93 +/- 0.12 vs 0.70 +/- 0.12 mumol/kg/min; p less than 0.05) were also lower after metformin treatment, while glucose oxidation increased from 0.9 +/- 0.2 vs 1.2 +/- 0.1 mg/kg/min. During the insulin clamp studies, whole body glucose disposal was higher both at the lower (2.1 +/- 0.4 vs 2.8 +/- 0.4 mg/kg/min) and higher insulin plateau (4.8 +/- 0.9 vs 6.3 +/- 0.9 mg/kg/min; p less than 0.01). Since no difference was apparent in glucose oxidation, the increase in glucose disposal was entirely accounted for by an improvement in non-oxidative glucose metabolism. Euglycemic hyperinsulinemia was followed by a reduction in plasma FFA concentration turnover rate that remained the same before and after metformin therapy. In conclusion, metformin treatment induces an improvement in glucose metabolism both in the basal and insulin-stimulated state.(ABSTRACT TRUNCATED AT 250 WORDS)