{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:45:05Z","timestamp":1791438305388,"version":"4.3.3"},"reference-count":129,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>This article summarizes the current understanding of the heterogeneity of type 1 diabetes from a June 2024 international Expert Forum organized by the editors of Diabetes, Diabetes Care, and Diabetologia. The Forum reviewed key factors contributing to the development and progression of type 1 diabetes and outlined specific, high-priority research questions. Knowledge gaps were identified, and, notably, opportunities to harness disease heterogeneity to develop personalized therapies were outlined. Herein, we summarize our discussions and review the heterogeneity of genetic risk and immunologic and metabolic phenotypes that influence and characterize type 1 diabetes progression (presented as a palette of risk factors). We discuss how these age-related factors determine disease aggressiveness (along gradients) and describe how variable immunogenetic pathways aggregate (into networks) to affect \u03b2-cell and other pancreatic pathologies to cause clinical disease at different ages and with variable severity (described as disease-related thresholds). Heterogeneity of pathogenesis and clinical severity opens avenues to prevention and intervention, including the potential of disease-modifying immunotherapy and islet cell replacement. We conclude with a call for 1) continued research to identify more factors contributing to the disease, both overall and in specific subgroups; 2) investigations focusing on both individuals who surpass metabolic and immune thresholds and develop diabetes and those who remain disease free with the same level of immunogenetic risk; and 3) efforts to identify where the current type 1 diabetes staging system may fall short and determine how it can be improved to capture and leverage heterogeneity in prevention and intervention strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title\/>\n                  <\/jats:sec>","DOI":"10.2337\/dbi25-0011","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:01:22Z","timestamp":1753884082000},"page":"1730-1747","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":7,"title":["The Heterogeneity of Type 1 Diabetes: Implications for Pathogenesis, Prevention, and Treatment\u20142024\n                    <i>Diabetes<\/i>\n                    ,\n                    <i>Diabetes Care<\/i>\n                    , and\n                    <i>Diabetologia<\/i>\n                    Expert Forum"],"prefix":"10.2337","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-8663","authenticated-orcid":false,"given":"Carmella","family":"Evans-Molina","sequence":"first","affiliation":[{"name":"Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine 1 , Indianapolis, IN"},{"name":"Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine 2 , Indianapolis, IN"},{"name":"Richard L. Roudebush VA Medical Center 3 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2456-2289","authenticated-orcid":false,"given":"Yuval","family":"Dor","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School 4 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-0499","authenticated-orcid":false,"given":"\u00c5ke","family":"Lernmark","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University CRC, Sk\u00e5ne University Hospital 5 , Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6099-2406","authenticated-orcid":false,"given":"Chantal","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Endocrinology, University of Leuven 6 , Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0426-3492","authenticated-orcid":false,"given":"Jeffrey R.","family":"Millman","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine 7 , St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5013-6075","authenticated-orcid":false,"given":"Raghavendra G.","family":"Mirmira","sequence":"additional","affiliation":[{"name":"Diabetes Research and Training Center, The University of Chicago 8 , Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flemming","family":"Pociot","sequence":"additional","affiliation":[{"name":"Translational Type 1 Diabetes Research, Department of Clinical and Translational Research, Steno Diabetes Center Copenhagen 9 , Herlev, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen 10 , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-4645","authenticated-orcid":false,"given":"Maria J.","family":"Redondo","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Texas Children\u2019s Hospital 11 , Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3872-7793","authenticated-orcid":false,"given":"Stephen S.","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Virginia 12 , Charlottesville, VA"}],"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":"Exeter Centre of Excellence for Diabetes Research, Department of Clinical and Biomedical Sciences, University of Exeter 13 , Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9253-838X","authenticated-orcid":false,"given":"Michael R.","family":"Rickels","sequence":"additional","affiliation":[{"name":"Institute for Diabetes, Obesity & Metabolism, University of Pennsylvania Perelman School of Medicine 14 , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1786-1531","authenticated-orcid":false,"given":"R. David","family":"Leslie","sequence":"additional","affiliation":[{"name":"Blizard Institute and St. Bartholomew\u2019s Hospital, Queen Mary University of London 15 , London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"2026062315013980800_B1","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1172\/JCI124611","article-title":"Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases","volume":"129","author":"Agache","year":"2019","journal-title":"J Clin Invest"},{"key":"2026062315013980800_B2","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s00125-023-05927-2","article-title":"The countdown to type 1 diabetes: when, how and why does the clock 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