title: Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia.
abstract: 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 (PPARalpha). Activation of PPARalpha could lead to increased hepatic oxidation of fatty acids and less synthesis of TG for VLDL assembly.
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Merle
authors.initials: M
authors.lastname: Myerson
authors.forename: Colleen
authors.initials: C
authors.lastname: Ngai
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jones
authors.forename: Steve
authors.initials: S
authors.lastname: Holleran
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: Lars
authors.initials: L
authors.lastname: Berglund
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
mesh_terms: D000368:Aged; D001055:Apolipoproteins B / Q000378:metabolism*; D018592:Cross-Over Studies; D048909:Diabetes Complications / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D001055:Apolipoproteins B; D019821:Simvastatin