蛋白质组学已用于研究2型糖尿病（T2D），但大部分可用数据来自白人参与者。在此，我们扩展了以前的工作，通过分析杰克逊心脏研究（JHS，n = 1,313）中自我确定的非洲裔美国人（AAs）的大型队列来进行。我们发现在空腹血浆中，使用基于单链DNA适配体亲和力法测量，调整年龄、性别和批次后发现325种与糖尿病发病有关的蛋白质（FDR-q <0.05）。其中一部分与已建立的糖尿病发展途径的标记（如脂肪过多、血糖过高和/或胰岛素抵抗）无关，表明可能存在与疾病发展相关的新的生物过程。在进一步调整BMI、空腹血浆葡萄糖（FPG）、胆固醇水平、高血压、他汀药物使用和肾功能后，36种关联仍然显著。其中12种，包括补体因子H（CFH）、甲酰胺转移酶-环形脱氨酶（FTCD）、丝氨酸/苏氨酸蛋白激酶17B（STK17B）和高迁移率群体蛋白B1（HMGB1）的顶级关联，在自我确定的白人队列-弗雷明翰心脏研究和马尔默饮食和癌症研究的元分析中复制，支持这些生物标志物的普适性。这些与糖尿病相关的蛋白质中的部分选择也改善了风险预测。因此，通过研究多样化的人群，我们揭示了新的以及广泛一般化的关联，提供了对与糖尿病相关的蛋白质组的更全面的理解。©2023年美国糖尿病协会。

Proteomics has been leveraged to study type 2 diabetes (T2D), but the majority of available data are from White participants. Here, we extend prior work by analyzing a large cohort of self-identified African Americans (AAs) in the Jackson Heart Study (JHS, n=1,313). We found 325 proteins associated with incident diabetes after adjusting for age, sex, and batch (FDR-q<0.05) measured using a single-stranded DNA aptamer affinity-based method in fasting plasma. A subset was independent of established markers of diabetes development pathways such as adiposity, glycemia, and/or insulin resistance-suggesting potential novel biological processes associated with disease development. Thirty-six associations remained significant after further adjustments for BMI, fasting plasma glucose (FPG), cholesterol levels, hypertension, statin use, and renal function. Twelve, including the top associations of complement factor H (CFH), formimidoyltransferase-cyclodeaminase (FTCD), serine/threonine-protein kinase 17B (STK17B), and high mobility group protein B1 (HMGB1), replicated in a meta-analysis of selfidentified White cohorts-the Framingham Heart Study and Malmö Diet and Cancer Study-supporting the generalizability of these biomarkers. A selection of these diabetes-associated proteins also improved risk prediction. Thus, we uncovered both novel and broadly generalizable associations by studying a diverse population, providing a more complete understanding of the diabetes associated proteome.© 2023 by the American Diabetes Association.