Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia

Merle Myerson, Colleen Ngai, Jeffrey Jones, Steve Holleran, Rajasekhar Ramakrishnan, Lars Berglund, Henry N. Ginsberg

Research output: Contribution to journalArticle

30 Scopus citations

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 receptorα (PPARα). Activation of PPARα could lead to increased hepatic oxidation of fatty acids and less synthesis of TG for VLDL assembly.

Original languageEnglish (US)
Pages (from-to)2735-2744
Number of pages10
JournalJournal of Lipid Research
Volume46
Issue number12
DOIs
StatePublished - Dec 2005
Externally publishedYes

Keywords

  • 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors
  • Diabetes mellitus
  • Hypertriglyceridemia
  • Low density lipoproteins
  • Statins
  • Triglycerides
  • Very low density lipoproteins

ASJC Scopus subject areas

  • Endocrinology

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