Abstract 10: Improving Postprandial Lipoprotein Apolipoprotein B-48 Metabolism in Statin-Treated Patients With Diabetes

Abstract

Background: Type 2 diabetics often have elevated plasma TG and apolipoprotein B-48 (apoB-48) concentrations, particularly during the postprandial (PP) period. Evidence suggests that apoB-48 plays a central role in the development of atherosclerosis. Statins are frontline therapy to reduce CVD risk, however, residual risk still remains, suggesting that additional interventions are required to further reduce CVD risk. Aim: To compare PP apoB-48 kinetics in optimally statin-treated diabetic men with a group of normolipidemic healthy controls, and to investigate the effect of niacin on apoB-48 kinetics in these diabetic men. Methods: Twelve type 2 diabetic men and fourteen age-matched non-diabetic controls were recruited. Diabetics required a statin-treated LDL-C < 2.5 mmol/L to enter the trial: they were randomized to rosuvastatin or rosuvastatin plus niacin (titrated from 1 to 2 g daily) for 12 weeks and then crossed to the alternate therapy (3 week washout). PP metabolic studies were performed at the end of each treatment period, and on a single occasion in control subjects. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. Blood samples were collected over 24 h. ApoB-48 tracer/tracee ratios were measured using GCMS. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a compartmental model. Results: Fasting plasma TG (+112%, p<0.01), but not apoB-48 was elevated in statin-treated diabetics compared with controls. Incremental AUC TG and apoB-48 (+194% and +79%, respectively, p<0.01) were higher in diabetics. PP apoB-48 PR was higher in diabetics (+96%, p<0.01) and FCR lower (-45%, p<0.05), compared with controls. Niacin significantly lowered TG, plasma C, LDL-C and apoB (all p<0.005). Fasting apoB-48 concentration was lowered with niacin (-33%, p=0.03). ApoB-48 FCR was not altered with niacin, but PP apoB-48 PR was lowered to control levels (-38%, p=0.02) on niacin. Conclusion: ApoB-48 PR and FCR are abnormal in statin-treated diabetics. Niacin reduces apoB-48 concentration by lowering apoB-48 PR. This effect may be beneficial for reducing atherogenic PP lipoproteins and may provide CVD risk benefit to patients with type 2 diabetes.