{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:48:01Z","timestamp":1782478081372,"version":"3.54.5"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":176,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Type 1 diabetes (T1D) is an autoimmune disease characterized primarily by T cell\u2010mediated pancreatic\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cell destruction, with islet autoantibodies serving as important biomarkers of autoimmune activity and risk progression. Early detection of immune imbalances before seroconversion may help identify individuals at increased risk before established autoimmunity develops. In this review, the proposed \u201cStage 0\u201d construct is framed as a hypothesis\u2010driven, preautoimmune research construct rather than an established clinical stage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This narrative review evaluates the proposed Stage 0 construct as a hypothesis\u2010driven, preautoimmune conceptual framework for T1D, summarizes genetic, environmental, metabolic, and immunological factors that may precede islet autoantibody seroconversion, and outlines research priorities for risk stratification and prevention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review searched PubMed and Google Scholar using MeSH and free\u2010text terms to identify studies on early T1D pathogenesis, genetics, immunity, omics, metabolism, biomarkers, screening, and prevention. English\u2010language human studies, mechanistic studies, reviews, and selected animal studies were included when relevant to early T1D biology. The SANRA framework was used to assess methodological quality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Content and Findings<\/jats:title>\n                    <jats:p>\n                      This review discusses Stage 0 as a proposed preautoimmune phase and evaluates factors that may affect T1D progression, including early signs of inflammation, metabolic changes, gut dysbiosis, and\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cell stress. Polygenic and HLA\u2010based risk scores may improve disease prediction, but their performance differs across ancestries and requires population\u2010specific validation. The evidence remains strongest for genetic risk and islet autoantibody status, whereas many preautoantibody biomarkers remain exploratory and require replication. Prevention strategies are reviewed across immune\u2010modulating, antigen\u2010specific, metabolic, microbiome\u2010oriented, and screening\u2010linked pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Existing evidence supports additional research into preautoimmune biological alterations prior to the emergence of autoantibodies; however, Stage 0 should not be recognized as a clinical stage at this time. Standard biomarkers, ancestry\u2010inclusive risk models, and prospective validation are essential before Stage 0 screening is considered for routine practice. Future research should determine whether this provisional framework can be translated into ethical, evidence\u2010based screening and prevention pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jdr\/9970365","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:03:27Z","timestamp":1782475407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extending the Eisenbarth Model: Stage 0 as a Provisional Framework for Early Risk Stratification and Prevention in Type 1 Diabetes"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2683-3071","authenticated-orcid":false,"given":"Maya","family":"Puhachova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0297-7023","authenticated-orcid":false,"given":"Huda 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