title: Weight reduction and the impaired plasma-derived free fatty acid oxidation in type 2 diabetic subjects.
abstract: 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-(13)C]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 micromol/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.
authors: Department of Human Biology, Nutrition Research Center, Maastricht University, 6200 MD Maastricht, The Netherlands. e.blaak@hb.unimaas.nl
authors: E E
authors: EE
authors: Blaak
authors: B H
authors: BH
authors: Wolffenbuttel
authors: W H
authors: WH
authors: Saris
authors: M M
authors: MM
authors: Pelsers
authors: A J
authors: AJ
authors: Wagenmakers
mesh_terms: D001158:Arteries; D001823:Body Composition; D002153:Calorimetry, Indirect; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D015431:Weight Loss
chemical_list: D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin