Plasma Free Fatty Acid Uptake and Oxidation Are Already Diminished in Subjects at High Risk for Developing Type 2 Diabetes

Plasma Free Fatty Acid Uptake and Oxidation Are Already Diminished in Subjects at High Risk for Developing Type 2 Diabetes Marco Mensink , Ellen E. Blaak , Marleen A. van Baak , Anton J.M. Wagenmakers and Wim H.M. Saris Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands Abstract The objective of this study was to investigate to what extent disturbances in fatty acid metabolism found in type 2 diabetes are already present in subjects at high risk for developing diabetes (i.e., impaired glucose tolerance [IGT]). Components of fatty acid metabolism were measured in male subjects with IGT during postabsorptive conditions and during 60 min of exercise (50% V o 2max ) with the use of the stable isotope tracer [U- 13 C]palmitate in combination with indirect calorimetry, and those values were compared with previously published findings in male type 2 diabetic and male obese subjects. No differences were found between groups in energy expenditure and in total fat and carbohydrate oxidation. Rate of appearance and rate of disappearance of plasma free fatty acid (FFA) were lower in subjects with IGT and type 2 diabetes compared with obese subjects ( P < 0.05). Plasma FFA oxidation was lower in subjects with IGT and type 2 diabetes compared with obese subjects at rest and tended to be lower during exercise (rest: 3.7 ± 0.3, 4.4 ± 0.6, and 6.9 ± 1.0 μmol · kg fat-free mass [FFM] −1 · min −1 , P < 0.01; exercise: 15.0 ± 1.7, 14.1 ± 1.9, and 19.6 ± 1.5 μmol · kg FFM −1 · min −1 for IGT, type 2 diabetic, and obese subjects, respectively, P = 0.07). Triglyceride-derived fatty acid oxidation, however, was elevated in subjects with IGT and type 2 diabetes during exercise (3.6 ± 1.4, 1.4 ± 1.4, and –4.0 ± 2.0 μmol · kg FFM −1 · min −1 for IGT, type 2 diabetic, and obese subjects, respectively; P < 0.05). These data demonstrate that male subjects with a prediabetic condition (IGT) have the same defects in fatty acid utilization as subjects with type 2 diabetes, suggesting that these disturbances may play an important role in the progression from IGT to type 2 diabetes. Footnotes Address correspondence and reprint requests to Dr. Marco Mensink, Department of Human Biology, Nutrition and Toxicology Research Institute (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. E-mail: m.mensink{at}hb.unimaas.nl . Received for publication 16 March 2001 and accepted