Abstract P270: Niacin Lowers Triglyceride-Rich Lipoprotein Apolipoprotein B-48 Secretion in Statin-Treated Type 2 Diabetics

Abstract

Background: Type 2 diabetic subjects often have hypertriglyceridemia and an increased concentration of apolipoprotein B-48 (apoB-48) in circulation, particularly during the postprandial period. There is an accumulating body of evidence to suggest that apoB-48 plays a central role in the development of atherosclerosis. Statins are the frontline therapy to reduce cardiovascular risk, however, a large residual risk still remains. This residual risk suggests that additional therapeutic interventions may be required to further reduce CVD risk. Aim: To investigate the effect of niacin on the metabolism of triglyceride-rich lipoprotein (TRL) apoB-48 in men with type 2 diabetes on background statin therapy. Methods: Twelve type 2 diabetic men were recruited for this randomized, cross-over design study. Patients required a statin-treated low density lipoprotein (LDL) cholesterol of less than 2.5 mmol/L to enter the trial. Patients were then randomized to rosuvastatin alone or rosuvastatin plus niacin (titrated up from 1 to 2 g daily) for a period of 12 weeks and then were crossed over to the alternate therapy with a 3 week washout period in between. Metabolic studies were performed at the end of each treatment period. A bolus intravenous infusion of D3-leucine was administered as subjects consumed a standardised high-fat liquid meal. Blood samples were collected over 24 hours and TRL apoB-48 tracer/tracee ratios were measured using gas chromatography-mass spectrometry. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a multicompartmental model. Results: Niacin significantly reduced triglyceride, plasma cholesterol, LDL cholesterol and apoB (all p<0.005). TRL apoB-48 concentration was lower with niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/L, p=0.03). ApoB-48 FCR was not altered with niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p=0.79). Basal apoB-48 PR (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p=0.04) and postprandial apoB-48 PR were significantly lower (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p=0.02) on niacin. Conclusion: Niacin reduces TRL apoB-48 concentration by lowering basal and postprandial apoB-48 PR. This effect on apoB-48 metabolism may be beneficial for reducing atherogenic postprandial TRL particles and may provide CVD risk benefit to patients with type 2 diabetes.