{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T21:40:54Z","timestamp":1782510054587,"version":"3.54.5"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aims to characterize the clinical spectrum, elucidate the temporal relationship and assess the causality of checkpoint inhibitor\u2010associated autoimmune diabetes mellitus (CIADM) in a cohort of patients receiving anti\u2010programmed cell death\u20101 (PD\u20101)\/anti\u2010programmed death ligand\u20101 (PD\u2010L1) inhibitor therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Individuals who developed CIADM were identified among 4382 hospitalized patients receiving PD\u20101\/PD\u2010L1 inhibitor therapy between 2020 and 2024. Demographic characteristics, oncological history, immune checkpoint inhibitor regimens, laboratory parameters (including glycemic control, C\u2010peptide and islet autoantibodies) and clinical outcomes were systematically collected. Causality was evaluated using the Naranjo algorithm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 4382 patients who received PD\u20101\/PD\u2010L1 inhibitors, seven (0.16%) were diagnosed with CIADM during the study period. Seven patients were predominantly male, with a median age of 52\u2009years (range: 44\u201362), and hepatocellular carcinoma was the most common primary malignancy (3\/7). All patients developed CIADM after a median of 8\u2009cycles (range: 5\u201323) of PD\u20101\/PD\u2010L1 inhibitors (sintilimab, camrelizumab, envafolimab or atezolizumab). Notably, 86% (6\/7) of patients presented with diabetic ketoacidosis (DKA) at onset. Severe pancreatic \u03b2\u2010cell dysfunction was universal, with undetectable fasting and postprandial C\u2010peptide levels. Islet autoantibodies were positive in only one patient. The Naranjo score indicated a \u2018probable\u2019 to \u2018highly probable\u2019 causal relationship in all cases. All patients required lifelong insulin therapy. Following glycemic stabilization, immunotherapy was successfully reinitiated in six patients without exacerbating hyperglycemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CIADM is a severe immune\u2010related adverse event (irAE) characterized by abrupt onset, a high rate of DKA, and profound insulin deficiency, often in the absence of conventional islet autoantibodies. A definitive causal link exists between PD\u20101\/PD\u2010L1 inhibitors and CIADM. Our findings underscore the necessity for proactive glycemic monitoring in patients undergoing ICI therapy, especially in populations such as middle\u2010aged males with cancers known to have specific demographic profiles (e.g., hepatocellular carcinoma). Importantly, the resumption of immunotherapy is feasible with careful management, highlighting the critical role of a multidisciplinary approach to optimize oncological and metabolic outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dme.70316","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:29:38Z","timestamp":1775017778000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The clinical spectrum and causal relationship assessment of checkpoint inhibitor\u2010associated autoimmune diabetes mellitus (CIADM): A retrospective observational study"],"prefix":"10.1111","volume":"43","author":[{"given":"Youjia","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an 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