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DK107014"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["UC4 DK117009"],"award-info":[{"award-number":["UC4 DK117009"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Individuals with single islet autoantibody positivity exhibit a highly variable risk for type 1 diabetes progression. We evaluated whether metabolic measures identify those at higher progression risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>Among first- and second-degree relatives of persons with type 1 diabetes who screened and confirmed positive for a single autoantibody in the TrialNet Pathway to Prevention Natural History study, we used Cox proportional hazards models to assess associations between metabolic measures and time to progression, defined as the development of multiple autoantibody\u2013positive or stage 3 type 1 diabetes. Random forest models were used to estimate the relative importance of each variable. Analyses were conducted in the overall cohort and stratified by age (0\u20138, \u22658\u201316, and \u226516 years).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Individuals with single autoantibody positivity exhibited wide variation in metabolic function. Measures incorporating both oral glucose tolerance test\u2013stimulated glucose and C-peptide to assess \u03b2-cell dysfunction showed strong and consistent associations with progression across age-groups and antibody profiles. Associations for traditional risk factors, isolated glucose or C-peptide measures, or indices of insulin resistance differed by age and autoantibody type. Data-driven cutoffs for combined metabolic measures identified small subsets at very high risk (&amp;gt;50% 2-year progression) and large low-risk groups with &amp;lt;10% 5-year progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\u03b2-Cell dysfunction is present in many individuals with single autoantibody positivity and is associated with an increased risk of disease progression. Incorporating stimulated measures of \u03b2-cell function alongside age and autoantibody profiles may enable more personalized monitoring, help identify persons most likely to benefit from disease-modifying therapies, and delineate lower-risk individuals who require less intensive surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc26-1111","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:06:02Z","timestamp":1788361562000},"update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2-Cell Dysfunction Identifies Individuals With Single Autoantibody Positivity at Increased Risk of Type 1 Diabetes Progression"],"prefix":"10.2337","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-954X","authenticated-orcid":false,"given":"Emily K.","family":"Sims","sequence":"first","affiliation":[{"name":"1Center for Diabetes and Metabolic Diseases, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"You","sequence":"additional","affiliation":[{"name":"2Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-0030","authenticated-orcid":false,"given":"Heba","family":"Ismail","sequence":"additional","affiliation":[{"name":"1Center for Diabetes and Metabolic Diseases, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmella","family":"Evans-Molina","sequence":"additional","affiliation":[{"name":"1Center for Diabetes and Metabolic Diseases, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Atkinson","sequence":"additional","affiliation":[{"name":"3Departments of Pathology and Pediatrics, University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay M.","family":"Sosenko","sequence":"additional","affiliation":[{"name":"4Diabetes Research Institute, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2371-2495","authenticated-orcid":false,"given":"Emanuele","family":"Bosi","sequence":"additional","affiliation":[{"name":"5Diabetes Research Institute, IRCCS San Raffaele Hospital and Vita Salute San Raffaele University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,9,2]]},"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/doi\/10.2337\/dc26-1111\/893787\/dc261111.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/doi\/10.2337\/dc26-1111\/893787\/dc261111.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:06:03Z","timestamp":1788361563000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/doi\/10.2337\/dc26-1111\/172429\/Cell-Dysfunction-Identifies-Individuals-With"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":0,"URL":"https:\/\/doi.org\/10.2337\/dc26-1111","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]},"article-number":"dc261111"}}