Introduction: Proteomics could improve our understanding of the etiology of diabetes. We sought to identify proteomic signatures associated with incident diabetes.
Method: We used data from the Atherosclerosis Risk in Communities (ARIC) Study (visit 2, 1990-92) in midlife (ages 47-70y) . We examined associations of 4955 plasma proteins measured using an aptamer-based platform in 11341 participants (∼50% women, ∼25% Black) without prevalent diabetes. We divided the data into discovery (2/3) and validation (1/3) sets. We used multivariable Cox regression to examine protein associations with incident diabetes (diagnosis or medication) . Statistical tests were based on Bonferroni corrected p-values.
Results: In the discovery set (n=7907) , 1443 diabetes events accrued over a median (IQR 12, 21) years. We identified 568 proteins associated (p<0.05/4955) with incident diabetes after demographic adjustment and 162 proteins after additional adjustment for lifestyle and cardiometabolic risk factors (Figure) . In the validation set (n=3434, 723 events) , 78 of the 162 proteins were statistically significantly (p<0.05/162) associated with incident diabetes, including established (e.g. adiponectin, growth hormone receptor) and novel hits (e.g. apoplipoprotein F, carboxypeptidase M) .
Conclusions: We identified multiple established and novel proteins associated with incident diabetes in midlife.
M.R. Rooney: None. J. Chen: None. O. Tang: None. C.M. Ballantyne: Consultant; Abbott Diagnostics, Althera Pharmaceuticals, Amarin Corporation, Amgen Inc., Arrowhead Pharmaceuticals, Inc., AstraZeneca, Corvidia Therapeutics, Denka Seiken, ESPERION Therapeutics, Inc., Genentech, Inc., Gilead Sciences, Inc., Illumina, Matinas BioPharma Inc, Merck & Co., Inc., New Amsterdam, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Regeneron Pharmaceuticals Inc., Roche Diagnostics, Sanofi. Research Support; Abbott Diagnostics, Akcea Therapeutics, Amgen Inc., Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Ionis Pharmaceuticals, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals Inc., Roche Diagnostics. E. Boerwinkle: None. J. Echouffo Tcheugui: None. C.E. Ndumele: None. J.S. Pankow: None. P. Lutsey: None. L.E. Wagenknecht: None. M. Grams: None. E. Selvin: Other Relationship; Wolters Kluwer. J. Coresh: Consultant; Healthy.io Ltd. Research Support; National Institutes of Health.