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Weight Reduction and the Impaired Plasma-Derived Free Fatty Acid Oxidation in Type 2 Diabetic Subjects¹

Departments of Human Biology, Endocrinology (B.H.R.W.), and Physiology (M.M.A.L.P.), Nutrition Research Center, Maastricht University, 6200 MD Maastricht, The Netherlands

Address all correspondence and requests for reprints to: Dr. E. E. Blaak, Department of Human Biology, Nutrition Research Center, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. E-mail: e.blaak{at}hb.unimaas.nl

In a previous study the oxidation of plasma free fatty acids (FFA) under baseline conditions and during exercise was lower in type 2 diabetic subjects compared with weight-matched controls. The present study intended to investigate 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 underwent a 10-week diet period. Body composition and substrate utilization during rest and during bicycle exercise (50% of maximum aerobic capacity) were determined before and after the diet (during weight-stable conditions). FFA metabolism was studied by means of the tracer [U-¹³C]palmitate. Rates of oxidation of plasma FFA were corrected with an acetate recovery factor. Additionally, activities of mitochondrial enzymes and cytosolic fatty acid-binding 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 disappearance of FFA decreased as a result of diet. The rates of appearance and disappearance of FFA during exercise were not different before and after diet. The oxidation of plasma-derived fatty acids tended to decrease after diet during baseline conditions (P = 0.10), whereas the plasma FFA oxidation during exercise was not different before and after the diet (14.1 ± 1.9 vs. 14.8 ± 1.8 µmol/kg fat-free mass·min). Skeletal muscle cytosolic fatty acid-binding protein and the activities of muscle oxidative enzymes did not 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 development of type 2 diabetes mellitus rather than resulting from the type 2 diabetic state.

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