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

  1. D. C. Chan1,†,
  2. S. J. Hamilton1,†,
  3. K. A. Rye2,3,4,
  4. G. T. Chew1,
  5. A. J. Jenkins4,
  6. G. Lambert2,5,
  7. G. F. Watts1,*

Article first published online: 26 MAR 2010

DOI: 10.1111/j.1463-1326.2010.01229.x

Issue

Diabetes, Obesity and Metabolism

Diabetes, Obesity and Metabolism

Volume 12, Issue 9, pages 752–756, September 2010

Additional Information

How to Cite

Chan, D. C., Hamilton, S. J., Rye, K. A., Chew, G. T., Jenkins, A. J., Lambert, G. and Watts, G. F. (2010), 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, Obesity and Metabolism, 12: 752–756. doi: 10.1111/j.1463-1326.2010.01229.x

Author Information

  1. 1

    Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia

  2. 2

    The Heart Research Institute, Sydney, Australia

  3. 3

    Faculty of Medicine, University of Sydney, Sydney, Australia

  4. 4

    Department of Medicine, University of Melbourne, Fitzroy, Australia

  5. 5

    Université de Nantes, Faculté de Médecine, Nantes, France

  1. †

    These authors contributed equally to this article.

*Prof. Gerald F. Watts, GPO Box X2213, Perth, Western Australia 6847, Australia. E-mail: gerald.watts@uwa.edu.au

Publication History

  1. Issue published online: 23 JUL 2010
  2. Article first published online: 26 MAR 2010
  3. Date submitted 12 October 2009; date of first decision 15 December 2009; date of final acceptance 22 March 2010

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Keywords:

  • fenofibrate;
  • PCSK9;
  • VLDL metabolism;
  • type 2 diabetes

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/m2) 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.

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