Weight reduction and the impaired plasma-derived free fatty acid oxidationin type 2 diabetic subjects

In a previous study the oxidation of plasma free fatty acids (FFA) under ba seline conditions and during exercise was lower in type 2 diabetic subjects compared with weight-matched controls. The present study intended to inves tigate the effect of weight reduction (very low calorie diet) on plasma FFA oxidation in seven type 2 diabetic male subjects (body fat, 37.4 +/- 1.2%; age, 51.3 +/- 3.4 yr; plasma glucose, 7.45 +/- 0.48 mmol/L). Subjects unde rwent a 10-week diet period. Body composition and substrate utilization dur ing rest and during bicycle exercise (50% of maximum aerobic capacity) were determined before and after the diet (during weight-stable conditions). FF A metabolism was studied by means of the tracer [U-C-13]palmitate. Rates of oxidation of plasma FFA were corrected with an acetate recovery factor. Ad ditionally, activities of mitochondrial enzymes and cytosolic fatty acid-bi nding protein were determined in biopsies from the vastus lateralis muscle before and after the diet. The very low calorie diet resulted in a weight loss of 15.3 kg (110.8 +/- 7 .4 vs. 95.5 +/- 5.8 kg; P < 0.01). The basal rates of appearance and disapp earance of FFA decreased as a result of diet. The rates of appearance and d isappearance of FFA during exercise were not different before and after die t. The oxidation of plasma-derived fatty acids tended to decrease after die t during baseline conditions (P = 0.10), whereas the plasma FFA oxidation d uring exercise was not different before and after the diet (14.1 +/- 1.9 vs . 14.8 +/- 1.8 mu mol/kg fat-free mass min). Skeletal muscle cytosolic fatt y acid-binding protein and the activities of muscle oxidative enzymes did n ot significantly change as a result of weight loss. In conclusion, considerable weight reduction did not significantly improve plasma-derived FFA oxidation under baseline conditions and during exercise, suggesting that this impairment reflects a primary defect leading to the d evelopment of type 2 diabetes mellitus rather than resulting from the type 2 diabetic state.