Postprandial Muscle Uptake of Free Fatty Acids (FFA) is not Elevated Despite Higher FFA Appearance Rate in Type 2 Diabetes Mellitus.

Excess exposure of non-adipose tissues to fatty acids is a key factor leading to insulin resistance and DM2. However, the underlying mechanism by which excess non-adipose tissue fatty acid exposure occurs and the role of lipotoxicity in human are still poorly understood. We hypothesized that increased postprandial FFA appearance (RaFFA) is associated with increased muscle uptake of FFA independent of plasma glucose level in subjects with DM2. FFA uptake and blood flow were determined by positron emission tomography-computed axial tomography (PET/CT) after intravenous injection of 14(R,S)-fluoro-[T8F]-6-thia-heptadecanoic acid (FTHA) and 11C-acetate in men with T2DM (n=5) and healthy men (n=6) during continuous oral intake of standard liquid meal for 6 hours. RaFFA was determined with intravenous infusion of [U-13C]-palmitate. Plasma glucose level was maintained at ~6 mmo1/1 in all participants with intravenous infusion of insulin and variable intravenous glucose infusion. As expected, FFA level and RaFFA were 28% (P<0.05) and 25% higher (P=NS) respectively in DM2 vs. healthy men. Muscle blood flow was 58% lower (P = 0.005) in DM2. Muscle FFA uptake was similar in DM2 vs. controls (0.051 ± 0.008 vs. 0.062 ± 0.008 μmol g-1 min-1, respectively). We conclude that postprandial muscle uptake of plasma FFA is not elevated in DM2 in face of increase plasma FFA availability and despite acute normalisation of plasma glucose level. Our results suggest that the plasma FFA pool is probably not the main source of excess exposure of non-adipose tissues to fatty acids in subjects with DM2.