Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.
Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.
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DOI：
10.1161/atvbaha.115.305415
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Reilly MP
中科院分区：
文献类型：
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作者：
Qamar A;Khetarpal SA;Khera AV;Qasim A;Rader DJ;Reilly MP
富含甘油三酯的脂蛋白（TRL）已成为独立于低密度脂蛋白胆固醇（LDL-C）水平的冠心病（CHD）的致病危险因素。载脂蛋白C-III（ApoC-III）通过抑制脂蛋白脂肪酶和肝脏摄取TRL来调节TRL代谢。导致ApoC-III功能丧失的突变降低TG并降低CHD风险，提示ApoC-III的因果作用。关于2型糖尿病（T2 DM）患者中ApoC-III、TG和动脉粥样硬化之间的关系的数据很少。在此，我们研究了2型糖尿病患者血浆ApoC-III、TG与冠状动脉钙化（CAC）之间的关系。在1422例T2 DM但无临床表现CHD受试者的横断面研究中测量了血浆ApoC-III水平。ApoC-III水平与总胆固醇（斯皮尔曼r=0.36）、TG（r=0.59）、LDL-C（r=0.16）、空腹血糖（r=0.16）和糖化血红蛋白（r=0.12）呈正相关（均P < 0.0001）。在年龄、性别和人种校正分析中，ApoC-III水平与CAC呈正相关（ApoC-III每SD增加，Tobit回归比（TRR）1.78，95% CI 1.27-2.50，P <0.001）。正如对中间介质的预期，当调整TG（TRR 1.43，95% CI 0.94-2.18，P=0.086）和单独调整VLDL-C（TRR 1.14，95% CI 0.75-1.71，P=0.53）时，这些结果减弱。在T2 DM患者中，血浆ApoC-III升高与较高的TG、较不利的心脏代谢表型和较高的CAC（亚临床动脉粥样硬化的指标）相关。因此，治疗性抑制ApoC-III可能是降低T2 DM患者血浆TRL和心血管风险的新策略。
Triglyceride-rich lipoproteins (TRL) have emerged as causal risk factors for developing coronary heart disease (CHD) independent of low-density lipoprotein cholesterol (LDL-C) levels. Apolipoprotein C-III (ApoC-III) modulates TRL metabolism through inhibition of lipoprotein lipase and hepatic uptake of TRL. Mutations causing loss-of-function of ApoC-III lower TG and reduce CHD risk, suggestive of a causal role for ApoC-III. Little data exist regarding the relationship of ApoC-III, TG, and atherosclerosis in type 2 diabetes mellitus (T2DM) patients. Here, we examined the relationships between plasma ApoC-III, TG and coronary artery calcification (CAC) in T2DM patients. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest CHD. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), TG (r=0.59), LDL-C (r=0.16), fasting glucose (r=0.16) and glycosylated hemoglobin (r=0.12) (P < 0.0001 for all). In age, gender, and race-adjusted analysis, ApoC-III levels were positively associated with CAC (Tobit regression ratio (TRR) 1.78, 95% CI 1.27–2.50 per SD-increase in ApoC-III, P <0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both TG (TRR 1.43, 95% CI 0.94–2.18, P=0.086) and separately for VLDL-C (TRR 1.14, 95% ci 0.75–1.71, P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher TG, less favorable cardiometabolic phenotypes, and higher CAC, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma TRLs and cardiovascular risk in T2DM.