Effect of niacin on high-density lipoprotein apolipoprotein A-I kinetics in statin-treated patients with type 2 diabetes mellitus.

OBJECTIVE To investigate the effect of extended-release (ER) niacin on the metabolism of high-density lipoprotein (HDL) apolipoprotein A-I (apoA-I) in men with type 2 diabetes mellitus on a background of optimal statin therapy. APPROACH AND RESULTS Twelve men with type 2 diabetes mellitus were recruited for a randomized, crossover design trial. Patients were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed over to the alternate therapy after a 3-week washout period. Metabolic studies were performed at the end of each treatment period. HDL apoA-I kinetics were measured after a standardized liquid mixed meal and a bolus injection of d3-leucine for 96 hours. Compartmental analysis was used to model the data. ER niacin significantly decreased plasma triglyceride, plasma cholesterol, non-HDL cholesterol, low-density lipoprotein cholesterol, and apoB (all P<0.05) and significantly increased HDL cholesterol and apoA-I concentrations (P<0.005 and P<0.05, respectively). ER niacin also significantly increased HDL apoA-I pool size (6,088 ± 292 versus 5,675 ± 305 mg; P<0.001), and this was attributed to a lower HDL apoA-I fractional catabolic rate (0.33 ± 0.01 versus 0.37 ± 0.02 pools/d; P<0.005), with no significant changes in HDL apoA-I production (20.93 ± 0.63 versus 21.72 ± 0.85 mg/kg per day; P=0.28). CONCLUSIONS ER niacin increases HDL apoA-I concentration in statin-treated subjects with type 2 diabetes mellitus by lowering apoA-I fractional catabolic rate. The effect on HDL metabolism was independent of the reduction in plasma triglyceride with ER niacin treatment. Whether this finding applies to other dyslipidemic populations remains to be investigated.