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.

This article contains supplementary material online at https://doi.org/10.2337/figshare.21830886.

This content is only available via PDF.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.

Article PDF first page preview

Article PDF first page preview
You do not currently have access to this content.