Fenofibrate concomitantly decreases serum proprotein convertase subtilisin/kexin type 9 and very-low-density lipoprotein particle concentrations in statin-treated type 2 diabetic patients

Diabetes Obes Metab. 2010 Sep;12(9):752-6. doi: 10.1111/j.1463-1326.2010.01229.x.

Abstract

Aim: Diabetic dyslipidaemia, characterized by hypertriglyceridaemia as a result of elevated serum very-low-density lipoprotein (VLDL) concentrations, contributes to the increased risk of cardiovascular disease (CVD) in type 2 diabetes (T2DM). Proprotein convertase subtilisin/kexin type 9 (PCSK9) may play a role in regulating VLDL metabolism. We investigated the effect of fenofibrate on serum PCSK9 and VLDL particle concentrations in T2DM patients already receiving statin therapy.

Methods: In a double-blind randomized crossover study, 15 statin-treated T2DM patients (63 +/- 8 years, body mass index (BMI) 29 +/- 3 kg/m(2)) were treated with fenofibrate (145 mg/day) or matching placebo for 12 weeks. Serum PCSK9 concentrations were measured by immunoassay. VLDL particle concentration and size were determined by nuclear magnetic resonance spectroscopy.

Results: Fenofibrate decreased serum triglycerides (-23%), VLDL-triglycerides (-51%), total cholesterol (-11%), LDL-cholesterol (-16%), apolipoprotein B-100 (-16%), apolipoprotein C-III (-20%) and PCSK9 (-13%) concentrations compared with placebo (p < 0.05). Fenofibrate also decreased serum concentrations of large (-45%), medium (-66%) and small VLDL (-67%) particles (p < 0.05), without altering VLDL particle size. Serum PCSK9 reduction correlated with decreases in total (r = 0.526, p = 0.044) and small (r = 0.629, p = 0.021) VLDL particle concentrations.

Conclusions: Fenofibrate concomitantly decreased serum PCSK9 and VLDL particle concentrations in statin-treated T2DM patients. These findings support a mechanistic link between PCSK9 and VLDL metabolism, possibly through an effect of PSK9 on VLDL receptor degradation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticholesteremic Agents / pharmacology*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / prevention & control
  • Double-Blind Method
  • Dyslipidemias / drug therapy
  • Dyslipidemias / metabolism
  • Female
  • Fenofibrate / pharmacology*
  • Humans
  • Lipoproteins, VLDL / metabolism*
  • Male
  • Middle Aged
  • Proprotein Convertase 9
  • Proprotein Convertases / metabolism
  • Serine Endopeptidases / metabolism*

Substances

  • Anticholesteremic Agents
  • Lipoproteins, VLDL
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases
  • Fenofibrate