Plasma free fatty acid uptake and oxidation are already diminished in subjects at high risk for developing type 2 diabetes

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 su bjects at high risk for developing diabetes (i.e., impaired glucose toleran ce [IGT]). Components of fatty acid metabolism were measured in male subjec ts with IGT during postabsorptive conditions and during 60 min of exercise (50% Vo(2max)) with the use of the stable isotope tracer [U-C-13]palmitate in combination with indirect calorimetry, and those values were compared wi th previously published findings in male type 2 diabetic and male obese sub jects. No differences were found between groups in energy expenditure and i n total fat and carbohydrate oxidation. Rate of appearance and rate of disa ppearance of plasma free fatty acid (FFA) were lower in subjects with IGT a nd type 2 diabetes compared with obese subjects (P < 0.05). Plasma FFA oxid ation was lower in subjects with IGT and type 2 diabetes compared with obes e subjects at rest and tended to be lower during exercise (rest: 3.7 +/- 0. 3, 4.4 +/- 0.6, and 6.9 +/- 1.0 mu mol (.) kg fat-free mass [FFM](-1) (.) m in(-1), P < 0.01; exercise: 15.0 +/- 17, 14.1 +/- 1.9, and 19.6 +/- 1.5 mu mol (.) 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 mu mol (.) kg FFM-1 (.) min(-1) fo r 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 diabete s, suggesting that these disturbances may play an important role in the pro gression from IGT to type 2 diabetes.