OBJECTIVE Coronary artery disease (CAD) is a major challenge in patients with type 2 diabetes (T2D). Coronary computed tomography angiography (CCTA) provides a detailed anatomic map of the coronary circulation. Proteomics are increasingly used to improve diagnostic and therapeutic algorithms. We hypothesized that the protein panel is differentially associated with T2D and CAD. RESEARCH DESIGN AND METHODS In CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation; a cohort of 528 individuals with no previous cardiovascular event undergoing CCTA), participants were grouped into CAD- (clean coronaries) and CAD+ (diffuse lumen narrowing or plaques). Plasma proteins were screened by aptamer analysis. Two-way partial least squares was used to simultaneously rank proteins by diabetes status and CAD. RESULTS Though CAD+ was more prevalent among participants with T2D (HbA1c 6.7 ± 1.1%) than those without diabetes (56 vs. 30%, P < 0.0001), CCTA-based atherosclerosis burden did not differ. Of the 20 top-ranking proteins, 15 were associated with both T2D and CAD, and 3 (osteomodulin, cartilage intermediate-layer protein 15, and HTRA1) were selectively associated with T2D only and 2 (epidermal growth factor receptor and contactin-1) with CAD only. Elevated renin and GDF15 and lower adiponectin were independently associated with both T2D and CAD. In multivariate analysis adjusting for the Framingham risk panel, patients with T2D were "protected" from CAD if female (P = 0.007), younger (P = 0.021), and with lower renin levels (P = 0.02). CONCLUSIONS 1) CAD severity and quality do not differ between participants with T2D and without diabetes, 2) renin, GDF15, and adiponectin are shared markers by T2D and CAD, 3) several proteins are specifically associated with T2D or CAD, and 4) in T2D, lower renin levels may protect against CAD.

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冠状动脉疾病和2型糖尿病：蛋白质组学研究。

目的冠状动脉疾病（CAD）是2型糖尿病（T2D）患者的主要挑战。冠状动脉计算机断层造影血管造影（CCTA）提供了冠状动脉循环的详细解剖图。蛋白质组学越来越多地用于改善诊断和治疗算法。我们假设蛋白质面板与T2D和CAD差异相关。研究设计和方法在CAPIRE（异常受试者中的冠状动脉粥样硬化：保护性和新颖的个人危险因素评估； 528名先前未经历过CCTA的未发生心血管事件的人群）中，参与者分为CAD-（冠状动脉清洁）和CAD +（弥漫性管腔）变窄或斑块）。通过适体分析筛选血浆蛋白。双向偏最小二乘用于同时通过糖尿病状态和CAD对蛋白质进行排名。结果尽管T2D参与者（HbA1c 6.7±1.1％）的CAD +患病率高于无糖尿病的参与者（56 vs. 30％，P <0.0001），但基于CCTA的动脉粥样硬化负担没有差异。在20种排名靠前的蛋白质中，有15种与T2D和CAD相关，而3种（骨调节蛋白，软骨中间层蛋白15和HTRA1）仅与T2D有选择性，而2种（表皮生长因子受体和contactin-1）相关。仅使用CAD。肾素和GDF15升高以及脂联素降低与T2D和CAD独立相关。在针对Framingham风险面板进行的多变量分析中，如果女性（P = 0.007），年轻（P = 0.021），肾素水平较低（P = 0.02），则T2D患者不受CAD的保护。