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Fenofibrate concomitantly decreases serum proprotein convertase subtilisin/kexin type 9 and very‐low‐density lipoprotein particle concentrations in statin‐treated type 2 diabetic patients
Author(s) -
Chan D. C.,
Hamilton S. J.,
Rye K. A.,
Chew G. T.,
Jenkins A. J.,
Lambert G.,
Watts G. F.
Publication year - 2010
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2010.01229.x
Subject(s) - medicine , fenofibrate , very low density lipoprotein , endocrinology , kexin , apolipoprotein b , pcsk9 , lipoprotein , chemistry , lipoprotein particle , cholesterol , ldl receptor
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.