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We tested associations of 4,955 plasma proteins (SomaScan version 4.0) with \u223c3-year progression from IFG (FG 100\u2013125 mg\/dL without diabetes) to diabetes (diagnosis, medication, or FG \u2265126 mg\/dL) using logistic regression models adjusted for demographics, cardiometabolic risk factors, and baseline glucose with Bonferroni correction (P &amp;lt; 10\u22125). We explored biological pathways enriched among the top proteins and calculated improvements in prediction (\u0394AUC and net reclassification using 3-year risk thresholds of 6% and 15% in 80% training and 20% internal validation subsamples). We validated results in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>There were 3,786 ARIC participants with IFG (mean [SD] age 57 [6] years, 52% female, 28% Black individuals). The 3-year cumulative incidence of diabetes was 6%. Six proteins were associated with \u223c3-year progression to diabetes, namely lower receptor-type tyrosine-protein phosphatase S (PTPRS), anthrax toxin receptor 2 (ANTXR2), adiponectin (ADIPOQ), ciliary neurotrophic factor receptor subunit \u03b1 (CNTFR), transmembrane protein 132C (TMEM132C), and higher ADAMTS-like protein 2 (ADAMTSL2). Altered carbohydrate metabolism and glycolysis were key pathways. Adding the six proteins to covariates improved discrimination (optimism-corrected AUC 0.81, \u0394AUC 0.03, P = 0.005) and net reclassification (training 12.2%, internal validation 12.0%) with predicted diabetes risk quintiles spanning &amp;lt;1% to \u223c20%. Two of the six proteins were validated in MESA (P &amp;lt; 0.008).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>We identified proteins associated with 3-year IFG progression, with improvements in diabetes risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc26-0498","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:46:03Z","timestamp":1782395163000},"page":"1490-1497","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic Signatures of 3-Year Progression From Impaired Fasting Glucose to Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study"],"prefix":"10.2337","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5607-4848","authenticated-orcid":false,"given":"Mary 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MD"},{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health 2 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keenan A.","family":"Walker","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging 4 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie M.","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine 5 , Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boerwinkle","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Science, University of Texas Health Science Center 6 , Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanika N.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois Chicago 7 , Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1603-282X","authenticated-orcid":false,"given":"Chiadi E.","family":"Ndumele","sequence":"additional","affiliation":[{"name":"Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health 2 , Baltimore, MD"},{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University 8 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Pankow","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Community Health, School of Public Health, University of Minnesota 9 , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan 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