HDL biology
Fenofibrate shifts HDL from large HDL2 to small HDL3 particles over 5 years in type 2 diabetes without changing CETP, PLTP, or LCAT activity (Diabetologia 2007)
Original title: Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus
In a statin-free subset of the FIELD study, 171 participants with type 2 diabetes in Helsinki were randomized to micronised fenofibrate (200 mg/day) or placebo, with VLDL and HDL subspecies separated by ultracentrifugation at baseline, year 2, and year 5. Fenofibrate reduced plasma triacylglycerol by 26%, driven by a marked reduction in VLDL1 triacylglycerol (0.62 vs 0.29 mmol/l, P < 0.001), and increased LDL size (delta 0.80 nm, P < 0.001). Total HDL cholesterol was similar between groups, but HDL2 cholesterol decreased by 27.5% at year 5 (P < 0.001) while HDL3 cholesterol increased by 13.0% (P < 0.001); apoA-I was unaffected while apoA-II increased. Activities of cholesteryl ester transfer protein, phospholipid transfer protein, and lecithin:cholesterol acyltransferase were unchanged by fenofibrate.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.