Pang J, Chan D C, Hamilton S J, Tenneti V S, Watts G F, Barrett P H R
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Combined Universities Centre for Rural Health, University of Western Australia, Geraldton, Western Australia, Australia.
Diabetes Obes Metab. 2016 Apr;18(4):384-91. doi: 10.1111/dom.12622. Epub 2016 Jan 28.
To investigate the effects of extended-release (ER) niacin on apolipoprotein B-48 (apoB-48) kinetics in statin-treated patients with type 2 diabetes (T2DM).
A total of 12 men with T2DM were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed to the alternate therapy. Postprandial metabolic studies were performed at the end of each treatment period. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. ApoB-48 kinetics were determined using stable isotope tracer kinetics with fractional catabolic rates (FCRs) and secretion rates derived using a non-steady-state compartmental model. Area-under-the-curve (AUC) and incremental AUC (iAUC) for plasma triglyceride and apoB-48 were also calculated over the 10-h period after ingestion of the fat meal.
In statin-treated patients with T2DM, apoB-48 concentration was lower with ER niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/l, p = 0.03) compared with statin alone. Postprandial triglyceride and apoB-48 AUC were also significantly lower on ER niacin treatment (-15 and -26%, respectively; p < 0.05), without any change to triglyceride and apoB-48 iAUC. ApoB-48 secretion rate in the basal state (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p = 0.04) and number of apoB-48-containing particles secreted in response to the fat load (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p = 0.02) were lower on ER niacin. ApoB-48 FCR was not altered with ER niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p = 0.79).
ER niacin reduces apoB-48 concentration by lowering fasting and postprandial apoB-48 secretion rate. This effect may be beneficial for lowering atherogenic postprandial lipoproteins and may provide cardiovascular disease risk benefit in patients with T2DM.
研究缓释烟酸对接受他汀类药物治疗的2型糖尿病（T2DM）患者载脂蛋白B - 48（apoB - 48）动力学的影响。
总共12名T2DM男性患者被随机分为接受瑞舒伐他汀治疗组或瑞舒伐他汀加缓释烟酸治疗组，为期12周，然后交叉接受替代治疗。在每个治疗期结束时进行餐后代谢研究。当受试者食用高脂流质餐时给予D3 - 亮氨酸示踪剂。使用稳定同位素示踪动力学，通过非稳态房室模型得出的分解代谢率（FCR）和分泌率来测定apoB - 48动力学。在摄入脂肪餐后的10小时内还计算了血浆甘油三酯和apoB - 48的曲线下面积（AUC）和增量AUC（iAUC）。
在接受他汀类药物治疗的T2DM患者中，与单独使用他汀类药物相比，使用缓释烟酸时apoB - 48浓度更低（8.24±1.98 vs 5.48±1.14 mg/l，p = 0.03）。在缓释烟酸治疗时，餐后甘油三酯和apoB - 48的AUC也显著降低（分别降低-15%和-26%；p < 0.05），而甘油三酯和apoB - 48的iAUC没有任何变化。缓释烟酸治疗时，基础状态下的apoB - 48分泌率（3.21±0.34 vs 2.50±0.31 mg/kg/天；p = 0.04）以及对脂肪负荷反应时分泌的含apoB - 48颗粒数量（1.35±0.19 vs 0.84±0.12 mg/kg；p = 0.02）更低。缓释烟酸未改变apoB - 48的FCR（8.78±1.04 vs 9.17±1.26池/天；p = 0.79）。
缓释烟酸通过降低空腹和餐后apoB - 48分泌率来降低apoB - 48浓度。这种作用可能有助于降低餐后致动脉粥样硬化脂蛋白水平，并可能为T2DM患者带来心血管疾病风险获益。
