{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:27:05Z","timestamp":1777984025760,"version":"3.51.4"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"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:p>Autoimmune diabetes is a rare but severe endocrine toxicity induced by immune checkpoint inhibitor (ICI) treatment. It is unclear if ICI causes selective islet toxicity or non-selective pancreas toxicity. We analyzed 11 patients treated with ICI who developed ICI-related autoimmune diabetes. Eight patients had lipase and\/or amylase tested on the same day of diagnosis of autoimmune diabetes. Among them, 75% (6\/8) had normal lipase and 100% (6\/6) had normal amylase. There was no correlation between glucose level at onset and biochemical pancreatitis. We characterized the clinical features of ICI-induced autoimmune diabetes. Fifty-five percent (6\/11) of patients tested positive for GAD65 autoantibodies, and 55% (6\/11) developed diabetic ketoacidosis at manifestation of hyperglycemia. In all 11 patients, C-peptide levels were low in the presence of hyperglycemia. ICI-induced thyroiditis was found in 64% (7\/11), of which 36% (4\/11) were newly diagnosed with thyroiditis while the remaining 27% (3\/11) had pre-existing hypothyroidism followed by ICI-induced thyroiditis. Additionally, 27% (3\/11), developed ICI-induced hypophysitis. Thyroiditis and autoimmune diabetes coexisted in all patients with ICI-induced hypophysitis. The median time from ICI treatment to the onset of autoimmune diabetes was 11 weeks. Our data suggest that few patients had coexistent ICI-induced autoimmune diabetes and pancreatitis, suggesting ICI mainly caused selective islet toxicity.<\/jats:p>","DOI":"10.3389\/fendo.2021.620522","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T06:26:58Z","timestamp":1618295218000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Coexistence of Immune Checkpoint Inhibitor-Induced Autoimmune Diabetes and Pancreatitis"],"prefix":"10.3389","volume":"12","author":[{"given":"Amy L.","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee-Shing","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie E.","family":"McDonnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Min","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30261-4","article-title":"Cancer immunotherapy efficacy and patients\u2019 sex: a systematic review and meta-analysis","volume":"19","author":"Conforti","year":"2018","journal-title":"Lancet Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030738","article-title":"Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence","volume":"12","author":"Vaddepally","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.3064","article-title":"Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis","volume":"4","author":"Barroso-Sousa","year":"2018","journal-title":"JAMA Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1331","article-title":"Anti-PD1 Pembrolizumab Can Induce Exceptional Fulminant Type 1 Diabetes","volume":"38","author":"Gaudy","year":"2015","journal-title":"Diabetes Care"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-2349","article-title":"Precipitation of autoimmune diabetes with anti-PD-1 immunotherapy","volume":"38","author":"Hughes","year":"2015","journal-title":"Diabetes Care"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-015-1689-1","article-title":"Anti-programmed cell death-1 therapy and insulin-dependent diabetes: a case report","volume":"64","author":"Martin-Liberal","year":"2015","journal-title":"Cancer Immunol Immunother"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0889","article-title":"Anti-PD-1 and Anti-PDL-1 Monoclonal Antibodies Causing Type 1 Diabetes","volume":"38","author":"Mellati","year":"2015","journal-title":"Diabetes Care"},{"key":"B8","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s40425-016-0196-z","article-title":"Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy","volume":"4","author":"Lowe","year":"2016","journal-title":"J\u00a0Immunother Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0245-2","article-title":"Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic lung cancer","volume":"5","author":"Godwin","year":"2017","journal-title":"J Immunother Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0291","article-title":"Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review","volume":"181","author":"de Filette","year":"2019","journal-title":"Eur J Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-1465","article-title":"Increased Reporting of Immune Checkpoint Inhibitor-Associated Diabetes","volume":"41","author":"Wright","year":"2018","journal-title":"Diabetes Care"},{"key":"B12","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40425-019-0502-7","article-title":"Clinical characteristics and outcomes of immune checkpoint inhibitor-induced pancreatic injury","volume":"7","author":"Abu-Sbeih","year":"2019","journal-title":"J Immunother Cancer"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-S002","article-title":"2. 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