Carbohydrate and lipid metabolism of skeletal muscle in type 2 diabetic patients

Peripheral hyperinsulinaemia is the cause of metabolic changes that might contribute to the high incidence of macrovascular disease in patients with diabetes mellitus. In order to test this hypothesis muscle biopsies from 12 Type 2 diabetic patients and 14 age and sex matched non-diabetic patients, undergoing minor surgery, were obtained. The diabetic patients had significantly elevated fasting serum insulin (0.29±0.05 vs 0.6±0.03 nmol-l) and glucose (8.3±1.5 vs 4.6±0.5 mmol-l) and HbA1, levels (8.4±0.4 vs 5.0±0.2 per cent). The fasting and 2-h postprandial C-peptide levels were 0.99±0.25 vs 0.39±0.12 and 3.12±0.75 vs 1.09±0.34 nmol/l, respectively. The diabetic patients showed a marked elevation of triglyceride in the striated muscle biopsies compared to the non-diabetic controls (290±52 vs 48±6 μmol/g wet weight, p<0.001). Moreover, the activities of glucose-6-phosphate dehydrogenase (0,25±0.03 vs 0.13±0.01 U/g wet weight) and malic enzyme (0.15±0.01 vs 0.05±0.01 U/g wet weight), necessary for lipid synthesis, were significantly increased (both p<0.001) in the diabetic patients while the glycolytic enzymes, hexokinase (0.65±0.09 vs 1.82±0.11 U/g wet weight), pyruvate kinase (7.3±0.9 vs 13.2±0.9 U/g wet weight), phosphofructokinase (1.3±0.2 vs 2.6±0.2 U/g wet weight), and α-glycerophosphate dehydrogenase (7.3±0.5 vs 12.5±0.7 U/g wet weight) were decreased (all p<0.001). These data indicate substantial enhancement of lipid synthesis and decreased activity of glucose metabolism in skeletal muscles of peripherally hyperinsulinaemic diabetic patients.