Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Low HDL-cholesterol (HDL-C) is frequently accompanied by high triacylglycerol levels in diabetic dyslipidaemia, increasing the risk of CHD. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, fenofibrate treatment lowered triacylglycerol levels, but the initial 5% increase in HDL-C attenuated over 5 years. We explored the changes in VLDL and HDL subspecies during fenofibrate treatment in a statin-free FIELD cohort.

METHODS

We randomised 171 participants with type 2 diabetes mellitus, who had been recruited to the FIELD study in Helsinki, to micronised fenofibrate (200 mg/day) or placebo in double-blind study design. VLDL and HDL subspecies were separated by ultracentrifugation at baseline and at the second and fifth year. Apolipoprotein (apo)A-I and apoA-II were measured by immunoturbidometric methods and lipoprotein (Lp)A-I and LpAI-AII particles by differential immunoassay.

RESULTS

Fenofibrate reduced plasma triacylglycerol levels by 26%, resulting from a marked reduction in VLDL1 triacylglycerol (0.62 vs 0.29 mmol/l, p < 0.001). Fenofibrate caused an increase in LDL size (Delta 0.80 nm, p < 0.001). HDL-C was similar between the groups. HDL2-C was decreased by fenofibrate (-27.5% at 5th year, p < 0.001) and HDL3-C increased (13.0% at 5th year, p < 0.001). Fenofibrate had no effect on apoA-I, whereas apoA-II increased. Thus, LpA-I decreased while LpAI-AII increased. Activities of cholesteryl ester transfer protein, phospholipids transfer protein and lecithin:cholesterylacyl transferase were unchanged by fenofibrate. High homocysteine levels were associated with a slight decrease in HDL-C and apoA-I.

CONCLUSIONS/INTERPRETATION: Fenofibrate markedly reduced large VLDL particles and produced a clear shift in HDL subspecies towards smaller particles. The HDL3-C increase in conjunction with unchanged apoA-I [corrected] levels is a dilemma with regard to cardiovascular disease.