Impaired free fatty acid uptake in skeletal muscle but not in myocardium in patients with impaired glucose tolerance - Studies with PET and 14(R, S)-[F-18]fluoro-6-thia-heptadecanoic acid

Free fatty acids (FFAs) are an important substrate for myocardial and skele tal muscle metabolism, and increased availability and oxidation of FFA are suggested to be associated with insulin resistance. This study was undertak en to assess whether myocardial or muscle uptake of FFA is altered in patie nts with impaired glucose tolerance (IGT). Eight healthy men (control group ; age 48 +/- 1 years, BMI 25 +/- 1 kg/m(2), mean +/- SE) and eight men with IGT (glucose-intolerant group; age 49 +/- 1 years, BMI 29 +/- 1 kg/m2) wer e studied in the fasting state. Myocardial oxygen consumption and blood flo w and myocardial and femoral muscle FFA uptake rates were measured with pos itron emission tomography (PET) and [O-15]O-2, [O-15]H2O, [O-15]CO, and 14( R, S)-[F-18]fluoro-6-thia-heptadecanoic acid ([F-18]FTHA), a fatty acid tra cer trapped into the cell after undergoing initial steps of beta-oxidation. Serum glucose and insulin concentrations were higher in the glucose-intole rant group during the PET study, but FFA concentrations were comparable bet ween the groups. No differences between the groups were observed in the myo cardial blood flow, oxygen consumption, fractional FTHA uptake rates, or FF A uptake indices (5.6 +/- 0.4 vs. 5.2 +/- 0.4 pmol 100 g(-1) min(-1), gluco se-intolerant versus control, NS). In the femoral muscle, fractional FTHA u ptake (0.0062 +/- 0.0003 vs. 0.0072 +/- 0.0003 min(-1), P = 0.044) and FFA uptake indices (0.30 +/- 0.02 vs. 0.43 +/- 0.04 min(-1), P = 0.020) were si gnificantly lower in the gIucose-intolerant group than in the control group . In conclusion, when studied at the fasting state and normal serum FFA con centrations, subjects with IGT FFA uptake. This finding argues against the hypothesis that an increased oxidation of serum FFA, via the competition of glucose and FFA as fuel sources, is the primary cause for impaired periphe ral glucose utilization and insulin resistance commonly observed in IGT.