{"doi":"10.4093/dmj.2024.0455","title":"Risk Factors and Survival Outcomes of Immune Checkpoint Inhibitor-Induced Type 1 Diabetes Mellitus: A Retrospective Cohort Study","abstract":"<jats:p>Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment of metastatic solid tumors; however, they induce immune-related adverse events, such as ICI-induced type 1 diabetes mellitus (ICI-T1DM), a rare but serious condition requiring lifelong insulin therapy. We aimed to identify the risk factors and survival outcomes associated with ICI-T1DM to optimize screening and mitigate adverse effects.Methods: This retrospective cohort study analyzed 6,956 patients treated with ICIs at a tertiary care center between January 1, 2017, and February 28, 2023. ICI-T1DM was classified based on the need for persistent insulin therapy post-ICI and a C-peptide level &lt;1.0 ng/mL. Patient demographics, clinical characteristics, treatment details, and survival outcomes were examined.Results: ICI-T1DM was identified in 32 patients (0.46%) with a median onset time of 41 weeks. Significant risk factors included pre-existing diabetes (hazard ratio [HR], 2.352; 95% confidence interval [CI], 1.140 to 4.854), combination therapy with anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (HR, 3.666; 95% CI, 1.224 to 10.979), prolonged ICI treatment (≥12 weeks; HR, 4.789; 95% CI, 1.806 to 12.701), and thyroid dysfunction (HR, 4.027; 95% CI, 1.847 to 8.779). ICI-T1DM occurrence and thyroid dysfunction were associated with improved survival (HR, 0.224; 95% CI, 0.093 to 0.539; and HR, 0.616; 95% CI, 0.566 to 0.670).Conclusion: Patients with pre-existing diabetes, combined anti–PD-1/PD-L1 and anti–CTLA-4 therapy, prolonged ICI treatment (≥12 weeks), and thyroid dysfunction are at high risk of developing ICI-T1DM. The observed survival benefits in patients with ICI-T1DM underscore the importance of aggressive glucose monitoring and patient education for early detection and management.</jats:p>","journal":"Diabetes &amp; Metabolism Journal","year":2026,"id":623053,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":256035,"name":"Yun Kyung Cho","orcid":"0000-0002-4089-1376","position":1,"is_corresponding":false},{"id":256032,"name":"Eun Hee Koh","orcid":"0000-0003-3829-0384","position":2,"is_corresponding":false},{"id":1610088,"name":"Sang-hyeok Go","orcid":"0000-0002-2738-496X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Risk Factors and Survival Outcomes of Immune Checkpoint Inhibitor-Induced Type 1 Diabetes Mellitus: A Retrospective Cohort Study","abstract":"<jats:p>Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment of metastatic solid tumors; however, they induce immune-related adverse events, such as ICI-induced type 1 diabetes mellitus (ICI-T1DM), a rare but serious condition requiring lifelong insulin therapy. We aimed to identify the risk factors and survival outcomes associated with ICI-T1DM to optimize screening and mitigate adverse effects.Methods: This retrospective cohort study analyzed 6,956 patients treated with ICIs at a tertiary care center between January 1, 2017, and February 28, 2023. ICI-T1DM was classified based on the need for persistent insulin therapy post-ICI and a C-peptide level &lt;1.0 ng/mL. Patient demographics, clinical characteristics, treatment details, and survival outcomes were examined.Results: ICI-T1DM was identified in 32 patients (0.46%) with a median onset time of 41 weeks. Significant risk factors included pre-existing diabetes (hazard ratio [HR], 2.352; 95% confidence interval [CI], 1.140 to 4.854), combination therapy with anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (HR, 3.666; 95% CI, 1.224 to 10.979), prolonged ICI treatment (≥12 weeks; HR, 4.789; 95% CI, 1.806 to 12.701), and thyroid dysfunction (HR, 4.027; 95% CI, 1.847 to 8.779). ICI-T1DM occurrence and thyroid dysfunction were associated with improved survival (HR, 0.224; 95% CI, 0.093 to 0.539; and HR, 0.616; 95% CI, 0.566 to 0.670).Conclusion: Patients with pre-existing diabetes, combined anti–PD-1/PD-L1 and anti–CTLA-4 therapy, prolonged ICI treatment (≥12 weeks), and thyroid dysfunction are at high risk of developing ICI-T1DM. The observed survival benefits in patients with ICI-T1DM underscore the importance of aggressive glucose monitoring and patient education for early detection and management.</jats:p>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40692269","pmcid":"PMC12813390","openalex_id":"https://openalex.org/W4412579853","authors":[],"funders":[],"total_grants":0,"fwci":1.4718,"citation_percentile":0.83763682,"influential_citations":0,"citation_trend":[{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://www.e-dmj.org/upload/pdf/dmj-2024-0455.pdf","host_type":"journal"},{"url":"https://www.e-dmj.org/upload/pdf/dmj-2024-0455.pdf","host_type":"publisher"},{"url":"http://e-dmj.org/upload/pdf/dmj-2024-0455.pdf","host_type":"publisher"},{"url":"http://e-dmj.org/journal/view.php?doi=10.4093/dmj.2024.0455","host_type":"publisher"},{"url":"https://doi.org/10.4093/dmj.2024.0455","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40692269","host_type":"repository"},{"url":"https://doaj.org/article/1a8df48f8aaa43e6ac889b92ffaded33","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12813390","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12813390/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12813390","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12813390?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer Immunotherapy and Biomarkers","Neuroendocrine Tumor Research Advances","Diabetes and associated disorders","Humans","Immune Checkpoint Inhibitors","Diabetes Mellitus, Type 1","Retrospective Studies","Male","Female","Risk Factors","Middle Aged","Adult","Neoplasms","Aged"],"mesh_terms":["Immune Checkpoint Inhibitors","Adult","Aged","Diabetes Mellitus, Type 1","Female","Humans","Male","Middle Aged","Neoplasms","Retrospective Studies","Risk Factors"],"keywords":["Medicine","Retrospective cohort study","Diabetes mellitus","Type 2 Diabetes Mellitus","Internal medicine","Cohort","Cohort study","Oncology","Endocrinology","Neoplasm metastasis","Survival analysis","risk factors","Diabetes Mellitus, Type 1","Immune Checkpoint Inhibitors"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T22:09:09.564657Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}