The effect of high-dose simvastatin on free fatty acid metabolism in patients with type 2 diabetes mellitus

Statins improve all major lipid fractions, reduce coronary heart disease risk, and may have a minor effect on glucose tolerance. A reduction in free fatty acid flux and concentrations could be partly responsible for these effects. We measured nocturnal and postprandial plasma palmitate concentrations and rate of appearance (Ra) on 2 occasions in 12 obese dyslipidemic subjects with type 2 diabetes mellitus, using a single-blind, crossover format (placebo followed by simvastatin, 80 mg/d), and also on 1 occasion in 6 untreated control subjects. The diabetic subjects had increased average nocturnal (127 ± 13 vs 80 ± 10 μmol/L, P < .05) and 2-hour postprandial (49 ± 6 vs 17 ± 2 μmol/L, P < .001) palmitate concentrations, as well as increased nocturnal (31.6 ± 3.7 vs 19.5 ± 3.7 mmol/m2 over 9 hours, P < .05) and postprandial (11.5 ± 3.7 vs 5.5 ± 3.7 mmol/m2 every 4 hours, P < .005) integrated palmitate Ra compared to normal controls. High-dose simvastatin reduced serum triglycerides by 35% but had no effect on plasma palmitate concentrations or Ra. These results suggest that the triglyceride-lowering effect of statins is not mediated through an effect on FFA metabolism.