Apolipoprotein B-48 as a determinant of endothelial function in obese subjects with type 2 diabetes mellitus: effect of fenofibrate treatment.
Objective: Elevated triglyceride-rich lipoproteins may contribute to endothelial dysfunction in obese diabetic subjects. We investigated the association between plasma concentrations of chylomicron-related particles and endothelial function, and the corresponding responses to fenofibrate treatment.
Methods: Plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol concentrations were measured in 28 obese subjects with T2DM. Flow-mediated endothelium-dependent dilation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) in the brachial artery during reactive hyperaemia were examined by high-resolution ultrasound technique.
Results: In univariate analysis, plasma apoB-48 and RLP-cholesterol concentrations were inversely associated with brachial artery FMD (r = -0.425 and -0.423, respectively, P<0.05), but not with GTNMD. In regression models including BMI and HOMA score, plasma apoB-48 was an independent predictors (P<0.05) of brachial artery FMD (β coefficient = -0.384). Replacing HOMA-IR score with plasma triglyceride, adiponectin or CRP concentrations did not alter the findings. The subjects were then randomized to a 12-week treatment period of either 200mg micronized fenofibrate or matching placebo. Compared with the placebo group, fenofibrate treatment (200mg daily for 12 weeks) achieved significant increase in FMD (+34%) and reduction in plasma triglyceride (-42%), apoB-48 (-52%) and RLP-cholesterol (-51%) concentrations. The increase in FMD with fenofibrate was significantly associated with the corresponding decrease in plasma apoB-48 (r = -0.644, P<0.02) concentrations.
Conclusions: Our findings demonstrate an association between changes in lipid metabolism and improvement in endothelial function in patients with diabetic dyslipidaemia treated with fenofibrate that may involve the effect of apoB-48 on endothelium-dependent vasodilator function.