title: The effect of high-dose simvastatin on free fatty acid metabolism in patients with type 2 diabetes mellitus.
abstract: 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 (R(a)) 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 micromol/L, P<.05) and 2-hour postprandial (49+/-6 vs 17+/-2 micromol/L, P<.001) palmitate concentrations, as well as increased nocturnal (31.6+/-3.7 vs 19.5+/-3.7 mmol/m(2) over 9 hours, P<.05) and postprandial (11.5+/-3.7 vs 5.5+/-3.7 mmol/m(2) every 4 hours, P<.005) integrated palmitate R(a) compared to normal controls. High-dose simvastatin reduced serum triglycerides by 35% but had no effect on plasma palmitate concentrations or R(a). These results suggest that the triglyceride-lowering effect of statins is not mediated through an effect on FFA metabolism.
authors.affiliation: Endocrine Research Unit, Division of Endocrinology, Nutrition, and Metabolism, Mayo Clinic, Rochester, MN 55905, USA. isley.william@mayo.edu
authors.forename: William L
authors.initials: WL
authors.lastname: Isley
authors.forename: William S
authors.initials: WS
authors.lastname: Harris
authors.forename: John M
authors.initials: JM
authors.lastname: Miles
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010168:Palmitates / Q000097:blood; D019821:Simvastatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016037:Single-Blind Method; D014280:Triglycerides / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D010168:Palmitates; D014280:Triglycerides; D019821:Simvastatin