Fenofibrate decreases plasma ceramide in type 2 diabetes patients: A novel marker of CVD? - 22/03/18
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<0.001). These changes were strongly associated with those found for plasma sphingomyelin (r=0.80, P<0.001) and, to a lesser extent, for sphingosine-1-phosphate (r=0.34, P<0.001). Ceramide levels decreased in 73.5% of patients. In addition to the expected lipid changes (decreases in triglycerides, total cholesterol and LDL cholesterol, and increase in HDL cholesterol), fenofibrate also lowered plasma apoC-II (−11.1%, P<0.01), apoC-III (−24.6%; P<0.001), apoB100 (−27.0%, P<0.01) and sphingomyelinase (−7.6%, P<0.001), and increased plasma apoA-II (22.4%, P<0.001) as well as adiponectin (11.4%, P<0.001). No significant association was found between ceramide decrease and these modulations except for total cholesterol (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.
Le texte complet de cet article est disponible en PDF.Keywords : Apolipoprotein, Ceramide, Fenofibrate, Lipidomics, Type 2 diabetes
Abbreviations : CVD, LDL-C, TG, HDL-C, PPARα, ESI, LC–HRMS, m/z, RSD, S1P, Cer, SM, IS, apo, TC, S-ASM, PCA, OPLS
Plan
Vol 44 - N° 2
P. 143-149 - mars 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.