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.