title: Fenofibrate concomitantly decreases serum proprotein convertase subtilisin/kexin type 9 and very-low-density lipoprotein particle concentrations in statin-treated type 2 diabetic patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Metabolic Research Centre, University of Western Australia, Perth, Australia.
authors.forename: D C
authors.initials: DC
authors.lastname: Chan
authors.forename: S J
authors.initials: SJ
authors.lastname: Hamilton
authors.forename: K A
authors.initials: KA
authors.lastname: Rye
authors.forename: G T
authors.initials: GT
authors.lastname: Chew
authors.forename: A J
authors.initials: AJ
authors.lastname: Jenkins
authors.forename: G
authors.initials: G
authors.lastname: Lambert
authors.forename: G F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000517:prevention & control; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D008079:Lipoproteins, VLDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D011345:Fenofibrate