Oxidative and non-oxidative glucose metabolism in non-obese Type 2 (non-insulin-dependent) diabetic patients

Insulin resistance is a common feature of Type 2 (non-insulin-dependent) diabetes mellitus. This defect in insulin-mediated glucose metabolism could result from a defect in either glucose oxidation or non-oxidative glucose disposal. To examine this question, euglycaemic insulin clamp studies were performed in 16 normal weight Type 2 and 11 age-matched control subjects. In Type 2 diabetic patients the fasting plasma glucose concentration, 8.39±0.50 mmol/l, was allowed to decline (over 54±6 min) to 5.33±0.11 mmol/l before starting the insulin clamp. Total body glucose uptake was significantly decreased in Type 2 diabetic patients vs control subjects (148±15 vs 264±25 mg/min · m², p<0.001). Both total glucose oxidation (59±6 vs 89±6 mg/min·m², p<0.005) and non-oxidative glucose disposal (89±15 vs 179±24 mg/min · m², p<0.005) were significantly reduced in the Type 2 diabetic patients. Basal glucose oxidation was also reduced in the Type 2 diabetic patients (22±3 vs 38±5 mg/min·m², p<0.01). In conclusion, during the postabsorptive state and under conditions of euglycaemic hyperinsulinaemia, impairment of glucose oxidation and non-oxidative glucose disposal both contribute to the insulin resistance observed in normal weight Type 2 diabetic patients. Since lipid oxidation was normal in this group of diabetic patients, excessive non-esterified fatty acid oxidation cannot explain the defects in glucose disposal.