{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:42:17Z","timestamp":1791978137397,"version":"4.4.0"},"reference-count":28,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"NIH","award":["2U01DK106993-07"],"award-info":[{"award-number":["2U01DK106993-07"]}]},{"name":"NIH","award":["K08DK128628"],"award-info":[{"award-number":["K08DK128628"]}]},{"name":"NIH","award":["R01DK093954"],"award-info":[{"award-number":["R01DK093954"]}]},{"name":"NIH","award":["R01DK121929"],"award-info":[{"award-number":["R01DK121929"]}]},{"name":"NIH","award":["R01DK127308"],"award-info":[{"award-number":["R01DK127308"]}]},{"name":"NIH","award":["R01DK133881"],"award-info":[{"award-number":["R01DK133881"]}]},{"name":"NIH","award":["R01DK142858"],"award-info":[{"award-number":["R01DK142858"]}]},{"name":"NIH","award":["U01DK127382-012"],"award-info":[{"award-number":["U01DK127382-012"]}]},{"name":"NIH","award":["U01DK127786"],"award-info":[{"award-number":["U01DK127786"]}]},{"name":"NIH","award":["UC4DK104166"],"award-info":[{"award-number":["UC4DK104166"]}]},{"name":"VA Merit","award":["I01BX001733"],"award-info":[{"award-number":["I01BX001733"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["227897\/Z\/23\/Z"],"award-info":[{"award-number":["227897\/Z\/23\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council"},{"name":"Breakthrough T1D","award":["1-FAC-2025-1632-A-N"],"award-info":[{"award-number":["1-FAC-2025-1632-A-N"]}]},{"name":"Breakthrough T1D","award":["3-SRA-2025-1738-S-B"],"award-info":[{"award-number":["3-SRA-2025-1738-S-B"]}]},{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helmsley Trust Foundation","award":["G-2507-08409"],"award-info":[{"award-number":["G-2507-08409"]}]},{"name":"National Institute for Health and Care Research Exeter Biomedical Research Centre"},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["16\/0005529"],"award-info":[{"award-number":["16\/0005529"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022690","name":"JDRF","doi-asserted-by":"publisher","award":["3-SRA-2019-827-S-B"],"award-info":[{"award-number":["3-SRA-2019-827-S-B"]}],"id":[{"id":"10.13039\/100022690","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Randox Laboratories Ltd"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>HbA1c thresholds used to define dysglycemia in autoantibody-positive individuals at risk for type 1 diabetes do not account for age-related increases in HbA1c and may overestimate progression risk in adults. We evaluated whether age-adjusted HbA1c or a higher HbA1c threshold improves risk stratification across age-groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>We analyzed 5,024 autoantibody-positive relatives (3,720 children and 1,304 adults) participating in the TrialNet Pathway to Prevention study. Age-related HbA1c effects were modeled using 6,273 adults from the population-based Exeter 10000 cohort. Progression risk was compared using the standard dysglycemia threshold (HbA1c \u22655.7% [39 mmol\/mol]), age-adjusted HbA1c, and an alternative threshold of HbA1c \u22656.0% (42 mmol\/mol).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Using HbA1c \u22655.7% (39 mmol\/mol), children had higher 1-year progression risk than adults among single autoantibody\u2013positive participants (38% [95% CI 28, 47] vs. 13% [7.2, 19]) and multiple autoantibody\u2013positive participants (55% [49, 60] vs. 38% [27, 47]) (both P &amp;lt; 0.001). Age adjustment reduced these differences; progression risk was similar among single autoantibody\u2013positive participants (38% [28, 47] vs. 27% [13, 39]; P = 0.32), with attenuated differences among multiple autoantibody\u2013positive participants. An HbA1c threshold \u22656.0% (42 mmol\/mol) yielded comparable progression risk between adults and children across autoantibody subgroups. In post hoc analyses, adults aged &amp;lt;30 years had progression risk similar to children (P = 0.1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Age-related variation in HbA1c influences dysglycemia classification in adults at risk for type 1 diabetes. Age-adjusted HbA1c or a higher HbA1c threshold (\u22656.0% [42 mmol\/mol]) in adults aged \u226530 years identifies individuals with progression risk comparable to children and may improve age-specific risk stratification in prevention settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc26-0446","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:45:01Z","timestamp":1778082301000},"page":"1262-1269","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":1,"title":["Accounting for Age-Related Increases in HbA1c More Accurately Quantifies Risk of Type 1 Diabetes Progression in Islet Autoantibody\u2013Positive Adults"],"prefix":"10.2337","volume":"49","author":[{"given":"Erin L.","family":"Templeman","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Science, University of Exeter Medical School 1 , Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Science, University of Exeter Medical School 1 , Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Science, University of Exeter Medical School 1 , Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane K.","family":"Wherett","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Hospital for Sick Children, University of Toronto 2 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Redondo","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Texas Children\u2019s Hospital 3 , Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Sherr","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine 4 , New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Petrelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan and Pio Albergo Trivulzio 5 , Milan, Italy"},{"name":"Cardiac-Thoracic-Metabolic Unit, Pio Albergo Trivulzio 6 , Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Pathology, University of Florida 7 , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falastin","family":"Salami","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University 8 , Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Lonier","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Columbia University Irving Medical Center 9 , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmella","family":"Evans-Molina","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine 10 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Sosenko","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, University of Miami 11 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Barroso","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Science, University of Exeter Medical School 1 , Exeter, U.K."},{"name":"Exeter Centre of Excellence for Diabetes Research (EXCEED), University of Exeter Medical School 12 , Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Oram","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Science, University of Exeter Medical School 1 , Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily K.","family":"Sims","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine 10 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3166-9685","authenticated-orcid":false,"given":"Lauric A.","family":"Ferrat","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Science, University of Exeter Medical School 1 , Exeter, U.K."},{"name":"Department of Genetic Medicine and Development, University of Geneva 13 , Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"2026062214533164200_B1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1056\/NEJMoa1902226","article-title":"An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes","volume":"381","author":"Herold","year":"2019","journal-title":"N Engl J Med"},{"key":"2026062214533164200_B2","doi-asserted-by":"crossref","first-page":"eabc8980","DOI":"10.1126\/scitranslmed.abc8980","article-title":"Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals","volume":"13","author":"Sims","year":"2021","journal-title":"Sci Transl Med"},{"key":"2026062214533164200_B3","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.2337\/dc15-1419","article-title":"Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association","volume":"38","author":"Insel","year":"2015","journal-title":"Diabetes Care"},{"key":"2026062214533164200_B4","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s00125-024-06205-5","article-title":"Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes","volume":"67","author":"Phillip","year":"2024","journal-title":"Diabetologia"},{"key":"2026062214533164200_B5","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.2337\/db10-0502","article-title":"Common variants at 10 genomic loci influence hemoglobin A1(C) levels via glycemic and nonglycemic pathways","volume":"59","author":"Soranzo","year":"2010","journal-title":"Diabetes"},{"key":"2026062214533164200_B6","doi-asserted-by":"crossref","first-page":"4284","DOI":"10.1182\/blood-2008-04-154112","article-title":"Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c","volume":"112","author":"Cohen","year":"2008","journal-title":"Blood"},{"key":"2026062214533164200_B7","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12902-019-0338-7","article-title":"Preventing misdiagnosis of diabetes in the elderly: age-dependent HbA1c reference intervals derived from two population-based study cohorts","volume":"19","author":"Masuch","year":"2019","journal-title":"BMC Endocr Disord"},{"key":"2026062214533164200_B8","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.2337\/diacare.25.8.1326","article-title":"Distribution of HbA1c levels for children and young adults in the U.S","volume":"25","author":"Saaddine","year":"2002","journal-title":"Diabetes Care"},{"key":"2026062214533164200_B9","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3109\/00365513.2013.783931","article-title":"Population-based pediatric reference intervals for HbA1c, bilirubin, albumin, CRP, myoglobin and serum enzymes","volume":"73","author":"R\u00f6d\u00f6\u00f6","year":"2013","journal-title":"Scand J Clin Lab Invest"},{"key":"2026062214533164200_B10","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.2337\/db14-0497","article-title":"HbA1c predicts time to diagnosis of type 1 diabetes in children at risk","volume":"64","author":"Helminen","year":"2015","journal-title":"Diabetes"},{"key":"2026062214533164200_B11","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/pedi.13297","article-title":"HbA1c percentiles and the association between BMI, age, gender, puberty, and HbA1c levels in healthy German children and adolescents","volume":"23","author":"Hovestadt","year":"2022","journal-title":"Pediatr Diabetes"},{"key":"2026062214533164200_B12","doi-asserted-by":"crossref","first-page":"e442","DOI":"10.1002\/edm2.442","article-title":"Effect of biological variation in HbA1c and blood glucose on the diagnosis of prediabetes","volume":"6","author":"Hempe","year":"2023","journal-title":"Endocrinol Diabetes Metab"},{"key":"2026062214533164200_B13","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.2337\/dc09-9033","article-title":"International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes","volume":"32","author":"International Expert Committee","year":"2009","journal-title":"Diabetes Care"},{"key":"2026062214533164200_B14","volume-title":"Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation.","author":"World Health Organization","year":"2011"},{"key":"2026062214533164200_B15","unstructured":"University of South Florida. TrialNet pathway to prevention of T1D. In: ClinicalTrials.gov. Bethesda, MD, National Library of Medicine, 2025. NLM Identifier: NCT00097292. Accessed 29 April 2026. Available from https:\/\/clinicaltrials.gov\/show\/NCT00097292"},{"key":"2026062214533164200_B16","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.2337\/dc25-0192","article-title":"Contrasting adult and pediatric populations in a cohort of at-risk relatives in the T1D TrialNet Pathway to Prevention Study","volume":"48","author":"Templeman","year":"2025","journal-title":"Diabetes Care"},{"key":"2026062214533164200_B17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12916-021-02054-w","article-title":"Choice of HbA1c threshold for identifying individuals at high risk of type 2 diabetes and implications for diabetes prevention programmes: a cohort study","volume":"19","author":"Rodgers","year":"2021","journal-title":"BMC Med"},{"key":"2026062214533164200_B18","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1210\/jc.2010-0293","article-title":"Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for National Institute of Diabetes and Digestive and Kidney Diseases consortia","volume":"95","author":"Bonifacio","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"2026062214533164200_B19","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00125-023-05877-9","article-title":"Islet Autoantibody Standardization Program: interlaboratory comparison of insulin autoantibody assay performance in 2018 and 2020 workshops","volume":"66","author":"Marzinotto","year":"2023","journal-title":"Diabetologia"},{"key":"2026062214533164200_B20","volume-title":"Type 2 Diabetes: Prevention in People at High Risk.","author":"National Institute for Health and Care Excellence","year":"2012"},{"key":"2026062214533164200_B21","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s00125-019-4863-8","article-title":"Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes","volume":"62","author":"Thomas","year":"2019","journal-title":"Diabetologia"},{"key":"2026062214533164200_B22","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.2337\/dc22-2159","article-title":"Age of diagnosis does not alter the presentation or progression of robustly defined adult-onset type 1 diabetes","volume":"46","author":"Thomas","year":"2023","journal-title":"Diabetes Care"},{"key":"2026062214533164200_B23","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.2337\/dc08-0577","article-title":"Effect of aging on A1C levels in individuals without diabetes","volume":"31","author":"Pani","year":"2008","journal-title":"Diabetes Care"},{"key":"2026062214533164200_B24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0009-8981(93)90254-2","article-title":"Acceleration of hemoglobin glycation with aging","volume":"215","author":"Nakashima","year":"1993","journal-title":"Clin Chim Acta"},{"key":"2026062214533164200_B25","doi-asserted-by":"crossref","first-page":"eadz2251","DOI":"10.1126\/sciadv.adz2251","article-title":"Small things matter: lack of extraislet \u03b2 cells in type 1 diabetes","volume":"11","author":"Murrall","year":"2025","journal-title":"Sci Adv"},{"key":"2026062214533164200_B26","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.2337\/dc26-S002","article-title":"2. Diagnosis and classification of diabetes: Standards of Care in Diabetes\u20142026","volume":"49","author":"American Diabetes Association","year":"2026","journal-title":"Diabetes Care"},{"key":"2026062214533164200_B27","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.2337\/dc15-1429","article-title":"Defining pathways for development of disease-modifying therapies in children with type 1 diabetes: a consensus report","volume":"38","author":"Wherrett","year":"2015","journal-title":"Diabetes Care"},{"key":"2026062214533164200_B28","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.diabres.2009.12.013","article-title":"Effect of age and race\/ethnicity on HbA1c levels in people without known diabetes mellitus: implications for the diagnosis of diabetes","volume":"87","author":"Davidson","year":"2010","journal-title":"Diabetes Res Clin Pract"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/49\/7\/1262\/862793\/dc260446.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/49\/7\/1262\/862793\/dc260446.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T18:53:46Z","timestamp":1782154426000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/49\/7\/1262\/164788\/Accounting-for-Age-Related-Increases-in-HbA1c-More"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,5,6]]},"published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc26-0446","relation":{"has-preprint":[{"id-type":"doi","id":"10.2337\/figshare.32043963.v1","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.32043963.v2","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.32043963","asserted-by":"object"}]},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]}}}