Journal
JOURNAL OF LIPID RESEARCH
Volume 46, Issue 12, Pages 2735-2744Publisher
ELSEVIER
DOI: 10.1194/jlr.M500335-JLR200
Keywords
very low density lipoproteins; low density lipoproteins; triglycerides; 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors statins; diabetes mellitus; hypertriglyceridemia
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HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, crossover design trial to determine the effects of simvastatin, 80 mg/day, on plasma lipid and lipoprotein levels and on the metabolism of apolipoprotein B ( apoB) in VLDL, intermediate density lipoprotein (IDL), and LDL and of triglycerides (TGs) in VLDL. Simvastatin therapy decreased TG, cholesterol, and apoB significantly in VLDL, IDL, and LDL. These effects were associated with reduced production of LDL-apoB, mainly as a result of reduced secretion of apoB-lipoproteins directly into the LDL density range. Statin therapy also reduced hepatic production of VLDL-TG. There were no effects of simvastatin on the fractional catabolic rates of VLDL-apoB or -TG or LDL-apoB. The basis for decreased VLDL-TG secretion during simvastatin treatment is not clear, but recent studies suggest that statins may activate peroxisomal proliferator-activated receptor alpha (PPAR alpha). Activation of PPAR alpha could lead to increased hepatic oxidation of fatty acids and less synthesis of TG for VLDL assembly.
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