The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus

William L. Isley, John M. Miles, Bruce W. Patterson, William Harris

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Statins decrease triglycerides (TGs) in addition to decreasing low density lipoprotein-cholesterol. Although the mechanism for the latter effect is well understood, it is still unclear how TG decrease is achieved with statin therapy. Because hypertriglyceridemia is common in obese patients with type 2 diabetes mellitus, we studied triglyceride-rich lipoprotein triglyceride (TRL-TG) turnover in 12 such subjects using stable isotopically labeled glycerol. The diabetic subjects were studied after 12 weeks of placebo and after a similar course of therapy with simvastatin (80 mg daily) in a single-blind design. The results were compared with those from six nonobese nondiabetic control subjects. Simvastatin therapy reduced serum TGs by 35% in the diabetic subjects. Compared with the control subjects, TRL-TG secretion was almost 2-fold higher in the diabetic subjects (45.4 ± 4.9 vs. 24.4 ± 1.9 μmol/min; P <0.002) and was unaffected by simvastatin therapy. However, TRL-TG clearance was significantly increased in the diabetic subjects during simvastatin treatment compared with placebo (0.25 ± 0.03 vs. 0.16 ± 0.02 pools/h; P <0.002). This change was accompanied by a 49% increase in preheparin plasma lipase activity (P <0.03) and a 21% increase in postheparin LPL activity (P <0.01). Together, these findings provide strong evidence that the effect of statins on serum TGs is related to an increase in LPL activity, resulting in accelerated delipidation of TRL particles. The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)193-200
Number of pages8
JournalJournal of Lipid Research
Volume47
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Fingerprint

Simvastatin
Medical problems
Metabolism
Type 2 Diabetes Mellitus
Lipoproteins
Triglycerides
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Placebos
Therapeutics
Hypertriglyceridemia
Serum
Lipase
LDL Cholesterol
Glycerol
Plasmas

Keywords

  • Lipoprotein kinetics
  • Statin
  • Very low density lipoprotein

ASJC Scopus subject areas

  • Endocrinology

Cite this

The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus. / Isley, William L.; Miles, John M.; Patterson, Bruce W.; Harris, William.

In: Journal of Lipid Research, Vol. 47, No. 1, 01.2006, p. 193-200.

Research output: Contribution to journalArticle

Isley, William L. ; Miles, John M. ; Patterson, Bruce W. ; Harris, William. / The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus. In: Journal of Lipid Research. 2006 ; Vol. 47, No. 1. pp. 193-200.
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