Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients

- Diabetic patients have an important alteration of HDL composition and metabolism.
- Fenofibrate and niacin impact differently on HDL composition and metabolism.
- The HDL particles after fenofibrate and niacin treatment are different among them.
- None of the two drugs reverse type 2 diabetic patients HDL to normal state.
- HDL quality can explain the low clinical effectiveness of both drugs.

HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted. Thirty type 2 diabetic patients with low HDL were randomised to receive either fenofibrate (FFB) or niacin + laropiprant (ERN/LPR) as an add-on to simvastatin treatment for 12 weeks according to a crossover design. At the basal point and after each intervention period, physical examinations and comprehensive standard biochemical determinations and HDL metabolomics were performed. Thirty nondiabetic patients with normal HDL were used as a basal control group. ERN/LRP, but not FFB, significantly increased HDL cholesterol. Neither ERN/LRP nor FFB reversed the HDL particle size or particle number to normal. ERN/LRP increased apoA-I but not apoA-II, whereas FFB produced the opposite effect. FFB significantly increased Preβ1-HDL, whereas ERN/LRP tended to lower Preβ1-HDL. CETP and LCAT activities were significantly decreased only by ERN/LRP. PAF-AH activity in HDL and plasma decreased with the use of both agents. Despite their different actions on antioxidant parameters, none of the treatments induced detectable antioxidant improvements.ERN/LRP and FFB had strikingly different effects on HDL quantity and quality, as well as on HDL cholesterol concentrations. When prescribing HDL cholesterol increasing drugs, this differential action should be considered.