{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:52:08Z","timestamp":1753890728032,"version":"3.41.2"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"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>Immune checkpoint inhibitor (ICI)- and phosphatidylinositol-3-kinase inhibitor (PI3Ki)-related diabetes mellitus are common side effects of anti-tumor drug use that present mainly as hyperglycemia. Here, we present two case reports of diabetes mellitus caused by the use of tremelimumab and apalutamide, respectively, in cancer treatment, and a comprehensive, comparative review of the literature on these forms of diabetes. Case 1 presented with diabetic ketoacidosis and was diagnosed with ICI-related diabetes mellitus and treated with insulin. Case 2 was diagnosed with PI3Ki-related diabetes mellitus, and her blood glucose level returned to normal with the use of metformin and dapagliflozin. We systematically searched the PubMed database for articles on ICI- and PI3Ki-related diabetes mellitus and characterized the differences in clinical features and treatment between these two forms of diabetes.<\/jats:p>","DOI":"10.3389\/fendo.2023.1236946","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T11:27:43Z","timestamp":1693913263000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Immune checkpoint inhibitor\u2013 and phosphatidylinositol-3-kinase inhibitor\u2013related diabetes induced by antineoplastic drugs: two case reports and a literature review"],"prefix":"10.3389","volume":"14","author":[{"given":"Yue","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyao","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Gan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-0609","article-title":"Immune checkpoint inhibitor-associated diabetes: A single-institution experience","volume":"43","author":"Byun","year":"2020","journal-title":"Diabetes Care"},{"key":"B2","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":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/1758835920940939","article-title":"Targeting the PI3K\/Akt\/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer","volume":"12","author":"du Rusquec","year":"2020","journal-title":"Ther Adv Med Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813904","article-title":"Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer","volume":"380","author":"Andr\u00e9","year":"2019","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31200","article-title":"Endocrine dysfunction induced by immune checkpoint inhibitors: Practical recommendations for diagnosis and clinical management","volume":"124","author":"Barroso-Sousa","year":"2018","journal-title":"Cancer"},{"key":"B6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1210\/er.2018-00006","article-title":"Endocrine toxicity of cancer immunotherapy targeting immune checkpoints","volume":"40","author":"Chang","year":"2019","journal-title":"Endocr Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2014.1002731","article-title":"The mutually regulatory loop of epithelial-mesenchymal transition and immunosuppression in cancer progression","volume":"4","author":"Chen","year":"2015","journal-title":"Oncoimmunology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04248-x","article-title":"An autoimmune stem-like CD8 T cell population drives type 1 diabetes","volume":"602","author":"Gearty","year":"2022","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","first-page":"8295","DOI":"10.1038\/s41598-018-26471-9","article-title":"Interferon-gamma drives programmed death-ligand 1 expression on islet \u03b2 cells to limit T cell function during autoimmune diabetes","volume":"8","author":"Osum","year":"2018","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.12.043","article-title":"Screening of ZnT8 autoantibodies in the diagnosis of autoimmune diabetes in a large French cohort","volume":"478","author":"Garnier","year":"2018","journal-title":"Clin Chim Acta"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00423","article-title":"Checkpoint inhibitor-associated autoimmune diabetes is distinct from type 1 diabetes","volume":"104","author":"Tsang","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000030398","article-title":"Type 1 diabetes associated with immune checkpoint inhibitors for Malignant melanoma: A case report and review of 8 cases","volume":"101","author":"Ishiguro","year":"2022","journal-title":"Med (Baltimore)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2020-0054","article-title":"Is immune checkpoint inhibitor-associated diabetes the same as fulminant type 1 diabetes mellitus","volume":"20","author":"Kyriacou","year":"2020","journal-title":"Clin Med (Lond)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1530\/EDM-22-0387","article-title":"Toripalimab-associated diabetes mellitus: a case report from the community of Southern China","author":"Zhang","year":"2023","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01076-2","article-title":"Toripalimab: first global approval","volume":"79","author":"Keam","year":"2019","journal-title":"Drugs"},{"key":"B16","doi-asserted-by":"publisher","first-page":"15567","DOI":"10.1038\/s41598-020-72649-5","article-title":"Landscape of immune checkpoint inhibitor-related adverse events in Chinese population","volume":"10","author":"Li","year":"2020","journal-title":"Sci Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1007\/s13340-018-0362-2","article-title":"Characteristics and clinical course of type 1 diabetes mellitus related to anti-programmed cell death-1 therapy","volume":"10","author":"Baden","year":"2019","journal-title":"Diabetol Int"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e35276","DOI":"10.7759\/cureus.35276","article-title":"A case of pembrolizumab-induced diabetic ketoacidosis and hyperthyroidism in a patient with recurrent esophageal adenocarcinoma","volume":"15","author":"Salangsang","year":"2023","journal-title":"Cureus"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12597","article-title":"Genetics of type 1 diabetes","volume":"19","author":"Redondo","year":"2018","journal-title":"Pediatr Diabetes"},{"key":"B20","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/ng.3353","article-title":"Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk","volume":"47","author":"Hu","year":"2015","journal-title":"Nat Genet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.18.00005","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: american society of clinical oncology clinical practice guideline summary","volume":"14","author":"Brahmer","year":"2018","journal-title":"J Oncol Pract"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e245846","DOI":"10.1136\/bcr-2021-245846","article-title":"Immune checkpoint inhibitor-induced diabetes mellitus with pembrolizumab","volume":"15","author":"Zand Irani","year":"2022","journal-title":"BMJ Case Rep"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2016-217454","article-title":"Glucocorticoids did not reverse type 1 diabetes mellitus secondary to pembrolizumab in a patient with metastatic melanoma","volume":"2016","author":"Aleksova","year":"2016","journal-title":"BMJ Case Rep"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31921","article-title":"Phosphatidylinositol 3-kinase pathway genomic alterations in 60,991 diverse solid tumors informs targeted therapy opportunities","volume":"125","author":"Millis","year":"2019","journal-title":"Cancer"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.clbc.2019.08.011","article-title":"A systematic literature review of the prognostic and predictive value of PIK3CA mutations in HR(+)\/HER2(-) metastatic breast cancer","volume":"20","author":"Mollon","year":"2020","journal-title":"Clin Breast Cancer"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14281","article-title":"Novel breast cancer treatment leads to hyperglycaemia","volume":"37","author":"Bass","year":"2020","journal-title":"Diabetes Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1177\/15347354211073163","article-title":"Management of phosphatidylinositol-3-kinase inhibitor-associated hyperglycemia","volume":"21","author":"Goncalves","year":"2022","journal-title":"Integr Cancer Ther"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.27173","article-title":"The PI3K\/AKT pathway in obesity and type 2 diabetes","volume":"14","author":"Huang","year":"2018","journal-title":"Int J Biol Sci"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00218-4","article-title":"The present and future of PI3K inhibitors for cancer therapy","volume":"2","author":"Castel","year":"2021","journal-title":"Nat Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e156330","DOI":"10.1172\/jci.insight.156330","article-title":"Immune cells and their inflammatory mediators modify \u03b2 cells and cause checkpoint inhibitor-induced diabetes","volume":"7","author":"Perdigoto","year":"2022","journal-title":"JCI Insight"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00728","article-title":"Programmed cell death-1 inhibitor-induced type 1 diabetes mellitus","volume":"103","author":"Clotman","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S370244","article-title":"Ketoacidosis in a patient with type 2 diabetes requiring alpelisib: learnings and observations regarding alpelisib initiation and rechallenge","volume":"15","author":"Leung","year":"2022","journal-title":"Onco Targets Ther"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1177\/23247096221105249","article-title":"S.U.G.A.R: A case to outline tactics for the prevention of alpelisib-induced hyperglycemia","volume":"10","author":"Thomas","year":"2022","journal-title":"J Investig Med High Impact Case Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4183\/aeb.2022.115","article-title":"Alpelisib - Induced Hyperglycemia","volume":"18","author":"Ekanayake","year":"2022","journal-title":"Acta Endocrinol (Buchar)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.aace.2020.11.028","article-title":"Alpelisib-induced diabetic ketoacidosis: A case report and review of literature","volume":"7","author":"Carrillo","year":"2021","journal-title":"AACE Clin Case Rep"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.14796","article-title":"Alpelisib-induced diabetic ketoacidosis","volume":"13","author":"Nguyen","year":"2021","journal-title":"Cureus"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.19295","article-title":"Alpelisib-induced diabetic ketoacidosis in a non-diabetic patient","volume":"13","author":"Fugere","year":"2021","journal-title":"Cureus"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e349","DOI":"10.4158\/ACCR-2020-0452","article-title":"Diabetic ketoacidosis associated with alpelisib treatment of metastatic breast cancer","volume":"6","author":"Farah","year":"2020","journal-title":"AACE Clin Case Rep"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.20817","article-title":"Alpelisib-induced diabetic ketoacidosis in a patient with metastatic breast cancer","volume":"13","author":"Al Zeyoudi","year":"2021","journal-title":"Cureus"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1380","article-title":"Euglycemic diabetic ketoacidosis: A predictable, detectable, and preventable safety concern with SGLT2 inhibitors","volume":"38","author":"Rosenstock","year":"2015","journal-title":"Diabetes Care"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e2924","DOI":"10.1002\/dmrr.2924","article-title":"Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data","volume":"33","author":"Blau","year":"2017","journal-title":"Diabetes Metab Res Rev"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1177\/2324709617725351","article-title":"Ketoacidosis with canagliflozin prescribed for phosphoinositide 3-kinase inhibitor-induced hyperglycemia: A case report","volume":"5","author":"Bowman","year":"2017","journal-title":"J Investig Med High Impact Case Rep"},{"key":"B43","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41586-018-0343-4","article-title":"Suppression of insulin feedback enhances the efficacy of PI3K inhibitors","volume":"560","author":"Hopkins","year":"2018","journal-title":"Nature"},{"key":"B44","doi-asserted-by":"publisher","first-page":"bnz014 [pii]","DOI":"10.1210\/endrev\/bnz014","article-title":"Review: diabetes, obesity, and cancer-pathophysiology and clinical implications","volume":"41","author":"Lega","year":"2020","journal-title":"Endocr Rev"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2014","article-title":"Obesity and diabetes: the increased risk of cancer and cancer-related mortality","volume":"95","author":"Gallagher","year":"2015","journal-title":"Physiol Rev"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2793-9","article-title":"Incidence of diabetes among postmenopausal breast cancer survivors","volume":"56","author":"Lipscombe","year":"2013","journal-title":"Diabetologia"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602956103","article-title":"Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice","volume":"103","author":"Le May","year":"2006","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1236946\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T11:27:47Z","timestamp":1693913267000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1236946\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,5]]},"references-count":47,"alternative-id":["10.3389\/fendo.2023.1236946"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1236946","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2023,9,5]]},"article-number":"1236946"}}