Arsenault Benoit J, Kohli Payal, Lambert Gilles, DeMicco David A, Laskey Rachel, Messig Michael M, Kastelein John J P, Waters David D
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada; Département de médicine, Faculté de medicine, Université Laval, Québec, Canada.
Division of Cardiology, University of California, San Francisco, San Francisco, California.
Am J Cardiol. 2016 Aug 15;118(4):494-8. doi: 10.1016/j.amjcard.2016.05.044. Epub 2016 May 29.
Whether biomarkers associated with cardiovascular disease risk also predict incident diabetes mellitus (DM) is unknown. Our objective was to determine if a panel of 18 biomarkers previously associated with risk of cardiovascular disease also predicts incident DM in statin-treated patients with coronary artery disease (CAD). The Treating to New Targets (TNT) study is a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of coronary heart disease events. Fasting plasma levels of standard lipids and of 18 emerging CAD risk biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in a random sample of 1,424 TNT patients. After exclusion of patients with DM at baseline (n = 253), 101 patients developed DM during the median follow-up of 4.9 years. Patients with incident DM had lower levels of total and high-molecular weight adiponectin, lipoprotein-associated phospholipase A2 (Lp-PLA2), soluble receptor of advanced glycation end products, and vitamin D compared with patients without incident DM. In contrast, insulin, soluble CD40 ligand, and soluble intercellular adhesion molecule-1 levels were higher in patients with incident DM compared with those without. Plasma levels of C-reactive protein, cystatin C, lipoprotein(a), monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, neopterin, N-terminal fragment of pro-B-type natriuretic peptide, osteopontin, and soluble vascular cell adhesion molecule-1 were comparable in patients with and without incident DM. After multivariate adjustment, total and high-molecular weight adiponectin as well as Lp-PLA2 were negatively associated with incident DM. Results of this study suggest that plasma lipids and some emerging CAD risk biomarkers, such as adiponectin and Lp-PLA2, may be useful for predicting incident DM in statin-treated patients with stable CAD.
与心血管疾病风险相关的生物标志物是否也能预测糖尿病（DM）的发生尚不清楚。我们的目的是确定一组先前与心血管疾病风险相关的18种生物标志物是否也能预测接受他汀类药物治疗的冠心病（CAD）患者发生DM的情况。强化降脂治疗新目标（TNT）研究是一项随机试验，比较了高剂量（80毫克）与低剂量（10毫克）阿托伐他汀对冠心病事件二级预防的疗效。在1424名TNT患者的随机样本中，服用10毫克阿托伐他汀8周导入期后，测定了标准血脂和18种新出现的CAD风险生物标志物的空腹血浆水平。排除基线时患有DM的患者（n = 253）后，101名患者在中位随访4.9年期间发生了DM。与未发生DM的患者相比，发生DM的患者总脂联素和高分子量脂联素、脂蛋白相关磷脂酶A2（Lp-PLA2）、晚期糖基化终产物可溶性受体和维生素D水平较低。相比之下，发生DM的患者胰岛素、可溶性CD40配体和可溶性细胞间黏附分子-1水平高于未发生DM的患者。发生DM和未发生DM的患者血浆C反应蛋白、胱抑素C、脂蛋白（a）、单核细胞趋化蛋白-1、基质金属蛋白酶-9、髓过氧化物酶新蝶呤、B型利钠肽原N端片段、骨桥蛋白和可溶性血管细胞黏附分子-1水平相当。多变量调整后，总脂联素和高分子量脂联素以及Lp-PLA2与DM的发生呈负相关。本研究结果表明，血脂和一些新出现的CAD风险生物标志物，如脂联素和Lp-PLA2，可能有助于预测接受他汀类药物治疗的稳定CAD患者发生DM的情况。
