Fenofibrate decreases plasma ceramide in type 2 diabetes patients: A novel marker of CVD?

Abstract Aim The benefit of the lipid-lowering drug fenofibrate on cardiovascular outcomes is controversial. Our aim was to find new circulating markers to identify those patients most likely to benefit from fenofibrate prescription. Methods Analyses were conducted of plasma samples collected from 102 patients with type 2 diabetes, enrolled in the FIELD trial, before and after fenofibrate treatment (200mg/day). Non-targeted and targeted lipid analyses and apolipoprotein measurements were made using mass spectrometry methods. Results Lipidomics revealed a global decrease in ceramide after fenofibrate treatment confirmed by quantitative analysis (−18.2%, P r =0.80, P r =0.34, P P P P P P P r =0.20, P =0.047) and HDL protein components. At baseline, only elevated sphingolipid levels were significantly associated with ceramide reduction after fenofibrate treatment. Conclusion Fenofibrate lowers plasma ceramide independently of the usual lipid parameters. As ceramide is a strong marker of atherosclerosis, our study underpins the need to further evaluate its contribution to cardiovascular events in fenofibrate-treated patients.