{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:48:31Z","timestamp":1774936111629,"version":"3.50.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The glutamic acid decarboxylase autoantibody (GADA) test is a widely used marker to differentiate type 1 diabetes and type 2 diabetes in adults. We conducted a systematic review to estimate the sensitivity and specificity of the presence of GADA for T1D in adults with newly diagnosed diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a PubMed and Embase search for studies that report both the GADA result and type 1 versus type 2 diabetes in adults diagnosed with diabetes. We calculated the sensitivity and specificity for each study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 19 studies involving 11,760 patients from diverse geographic settings. Across these studies, the sensitivity of GADA for identifying adult-onset type 1 diabetes varied widely (range: 0.27 to 0.83), with a pooled estimate of 0.53 (95% CI: 0.46\u20130.60). In contrast, specificity was consistently high, with a pooled estimate of 0.93 (95% CI: 0.89\u20130.96). The positive and negative likelihood ratios were 7.3 (95% CI 4.8 to 11.3) and 0.51 (0.44 to 0.58), respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our review demonstrates that GADA has high specificity and moderate sensitivity for identifying adult-onset type 1 diabetes. As a limitation, factors such as assay choice and cut-off values, as well as heterogeneity of both the type 1 and type 2 diabetes groups with regard to unmeasured genetic influences may contribute to the variability in antibody prevalence between studies. Our pooled likelihood ratios for GADA results might be useful for developing clinical and algorithmic tools to distinguish adult-onset type 1 diabetes from type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1771950","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T04:11:27Z","timestamp":1774930287000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Accuracy of glutamic acid decarboxylase antibodies for the identification of adult-onset type 1 diabetes mellitus: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Mandy M.","family":"Shao","sequence":"first","affiliation":[{"name":"Diabetes Technology Society","place":["Burlingame, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agatha F.","family":"Scheideman","sequence":"additional","affiliation":[{"name":"Diabetes Technology Society","place":["Burlingame, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen M.","family":"Zhou","sequence":"additional","affiliation":[{"name":"University of California, Berkeley","place":["Berkeley, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Kohn","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda A.","family":"DiMeglio","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoe","family":"Quandt","sequence":"additional","affiliation":[{"name":"Diabetes Center and Department of Medicine, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cate","family":"Speake","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy N.","family":"Ho","sequence":"additional","affiliation":[{"name":"Diabetes Technology Society","place":["Burlingame, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Klonoff","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, Mills-Peninsula Medical Center (Sutter Health)","place":["San Mateo, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/dom.16628","article-title":"The pathophysiology, presentation and classification of type 1 diabetes","volume":"27","author":"Aamodt","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-0770","article-title":"Adult-onset type 1 diabetes: Current understanding and challenges","volume":"44","author":"Leslie","year":"2021","journal-title":"Diabetes Care"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05568-3","article-title":"The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"64","author":"Holt","year":"2021","journal-title":"Diabetologia"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-023-06004-4","article-title":"The challenges of identifying and studying type 1 diabetes in adults","volume":"66","author":"Thomas","year":"2023","journal-title":"Diabetologia"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/dc26-S002","article-title":"2. Diagnosis and classification of diabetes: Standards of care in diabetes\u20142026","volume":"49","year":"2025","journal-title":"Diabetes Care"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.suppl_2.S52","article-title":"Autoantibodies in diabetes","volume":"54","author":"Pihoker","year":"2005","journal-title":"Diabetes"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2022.110029","article-title":"Predicting misdiagnosed adult-onset type 1 diabetes using machine learning","volume":"191","author":"Cheheltani","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1059\/0003-4819-155-8-201110180-00009","article-title":"QUADAS-2: A revised tool for the quality assessment of diagnostic accuracy studies","volume":"155","author":"Whiting","year":"2011","journal-title":"Ann Intern Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvad160","article-title":"Understanding islet autoantibodies in prediction of type 1 diabetes","volume":"8","author":"Jia","year":"2023","journal-title":"J Endocr Soc"},{"key":"B11","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s43856-024-00478-y","article-title":"Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: A systematic review","volume":"4","author":"Felton","year":"2024","journal-title":"Commun Med (Lond)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.12.3193","article-title":"Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe","volume":"53","author":"Zinman","year":"2004","journal-title":"Diabetes"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0431","article-title":"A type 1 diabetes genetic risk score can identify patients with GAD65 autoantibody-positive type 2 diabetes who rapidly progress to insulin therapy","volume":"42","author":"Grubb","year":"2019","journal-title":"Diabetes Care"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.640251","article-title":"Islet autoimmunity in adults with impaired glucose tolerance and recently diagnosed, treatment na\u00efve type 2 diabetes in the Restoring Insulin SEcretion (RISE) Study","volume":"12","author":"Brooks-Worrell","year":"2021","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2337\/db21-0590","article-title":"Islet autoimmunity is highly prevalent and associated with diminished \u03b2-cell function in patients with type 2 diabetes in the Grade Study","volume":"71","author":"Brooks-Worrell","year":"2022","journal-title":"Diabetes"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvad179","article-title":"GAD65Abs are not associated with beta-cell dysfunction in patients with T2D in the GRADE Study","volume":"8","author":"Hampe","year":"2024","journal-title":"J Endocr Soc"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac632","article-title":"Data mining framework for discovering and clustering phenotypes of atypical diabetes","volume":"108","author":"Parikh","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-0181","article-title":"Reversion of \u03b2-cell autoimmunity changes risk of type 1 diabetes: TEDDY Study","volume":"39","author":"Vehik","year":"2016","journal-title":"Diabetes Care"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-1903","article-title":"Interaction of onset and duration of diabetes on the percent of GAD and IA-2 antibody-positive subjects in the type 1 diabetes genetics consortium database","volume":"34","author":"Tridgell","year":"2011","journal-title":"Diabetes Care"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2016.05.005","article-title":"Islet cell-associated autoantibodies in Ethiopians with diabetes mellitus","volume":"30","author":"Siraj","year":"2016","journal-title":"J Diabetes Complications"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/1056-8727(93)90016-r","article-title":"The ethnic distribution of antibodies to glutamic acid decarboxylase: Presence and levels of insulin-dependent diabetes mellitus in Europid and Asian subjects","volume":"7","author":"Zimmet","year":"1993","journal-title":"J Diabetes Complications"},{"key":"B22","doi-asserted-by":"publisher","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":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30051-2","article-title":"Novel subgroups of adult-onset diabetes and their association with outcomes: A data-driven cluster analysis of six variables","volume":"6","author":"Ahlqvist","year":"2018","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-031586","article-title":"Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults aged 18\u201350 years","volume":"9","author":"Lynam","year":"2019","journal-title":"BMJ Open"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1771950\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T04:11:30Z","timestamp":1774930290000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1771950\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":24,"alternative-id":["10.3389\/fendo.2026.1771950"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1771950","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"article-number":"1771950"}}