{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:58:49Z","timestamp":1790013529124,"version":"4.0.1"},"reference-count":86,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The discovery of insulin transformed type 1 diabetes (T1D) from a lethal disease to a chronic health condition where individuals can lead long and productive lives. However, T1D is still associated with considerable morbidity and mortality, underscoring the need for disease-modifying therapies to delay clinical onset and preserve residual pancreatic \u03b2-cell function in those newly diagnosed with T1D. Notably, the first disease-modifying therapy (teplizumab, a monoclonal antibody targeting CD3+ on T lymphocytes) was approved by the US Food and Drug Administration in November 2022 to delay the clinical onset of T1D, thus opening new avenues to treat T1D as an immunologic disease rather than simply as a metabolic disease with lifelong insulin administration. In this Scientific Statement, we will integrate and summarize information about the pathogenesis of T1D, highlight gaps in current knowledge, and propose future activities that may lead to additional approaches to treat the underlying autoimmunity and \u03b2-cell defects in diabetes. Hopefully, these efforts, when combined with other rapidly improving T1D therapeutics including automated insulin delivery and cell replacement therapy, will lead to better long-term outcomes for those living with T1D.<\/jats:p>","DOI":"10.1210\/clinem\/dgaf267","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:54:22Z","timestamp":1746172462000},"page":"2496-2508","source":"Crossref","is-referenced-by-count":14,"title":["Challenges and Opportunities for Understanding the Pathogenesis of Type 1 Diabetes: An Endocrine Society Scientific Statement"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-5244","authenticated-orcid":false,"given":"Aaron W","family":"Michels","sequence":"first","affiliation":[{"name":"Pediatrics-Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Anschutz Campus , Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-9296","authenticated-orcid":false,"given":"Todd M","family":"Brusko","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pediatrics, Diabetes Institute, College of Medicine, University of Florida , Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-8663","authenticated-orcid":false,"given":"Carmella","family":"Evans-Molina","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Medicine, Indiana University School of Medicine , Indianapolis, IN 46202 , USA"},{"name":"The Roudebush VA Medical Center , Indianapolis, IN 46202 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7622-5754","authenticated-orcid":false,"given":"Dirk","family":"Homann","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami , Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1160-6062","authenticated-orcid":false,"given":"Sarah J","family":"Richardson","sequence":"additional","affiliation":[{"name":"Islet Biology Exeter (IBEx), Department of Clinical and Biomedical Sciences, University of Exeter Medical School , Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-5786","authenticated-orcid":false,"given":"Alvin C","family":"Powers","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["USA"]},{"name":"VA Tennessee Valley Healthcare System , Nashville, TN 37212 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"issue":"7","key":"2025081215515900200_dgaf267-B1","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/s41591-021-01418-2","article-title":"100 years of insulin: celebrating the past, present and future of diabetes therapy","volume":"27","author":"Sims","year":"2021","journal-title":"Nat Med"},{"issue":"21","key":"2025081215515900200_dgaf267-B2","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1056\/NEJMoa1408214","article-title":"Glycemic control and excess mortality in type 1 diabetes","volume":"371","author":"Lind","year":"2014","journal-title":"N Engl J Med"},{"issue":"15","key":"2025081215515900200_dgaf267-B3","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1056\/NEJMoa1608664","article-title":"Mortality and cardiovascular disease in type 1 and type 2 diabetes","volume":"376","author":"Rawshani","year":"2017","journal-title":"N Engl J Med"},{"issue":"7","key":"2025081215515900200_dgaf267-B4","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"},{"issue":"583","key":"2025081215515900200_dgaf267-B5","doi-asserted-by":"crossref","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"},{"issue":"21","key":"2025081215515900200_dgaf267-B6","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1056\/NEJM198605223142106","article-title":"Type I diabetes mellitus. 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