Immune checkpoint inhibitor-associated diabetes: a single-institution experience
Open accessAbstract
OBJECTIVE: To characterize immune checkpoint inhibitor–associated diabetes mellitus (ICI-DM) in a single-institution case series. RESEARCH DESIGN AND METHODS: Retrospective chart review of 18 patients with new-onset ICI-DM following anti–programmed cell death protein 1 (PD-1)/anti–programmed cell death protein ligand 1 (PD-L1) therapy for advanced carcinomas. RESULTS: Of 18 patients, 9 had diabetic ketoacidosis (median glucose 27.92 mmol/L; median glucose before presentation 6.35 mmol/L). Median C-peptide at ICI-DM diagnosis was low, and it declined during follow-up. Median anti-PD-1/anti-PD-L1 duration before ICI-DM was 3.65 months (range 0.56–12.23 months). Time to ICI-DM onset was a median 1.4 months/3 ICI cycles and 6 months/10 cycles in those patients who were positive and negative for GAD65 autoantibodies, respectively. Time to ICI-DM onset was a median 2.5 months/3 ICI cycles and 4.8 months/8 cycles after anti-PD-L1 or anti-PD-1 therapy, respectively. Significant pancreatic atrophy was seen radiographically. CONCLUSIONS: ICI-DM presents abruptly, appears irreversible, is characterized by pancreatic atrophy, and may occur both earlier following PD-L1 blockade compared with PD-1 inhibition and in those who have positive GAD65 autoantibodies.
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Immune checkpoint inhibitors suppress physiologic blocks on immune responses, which can result in autoimmune toxicities, including autoimmune diabetes, with an incidence approximately ≤1%.
“Immune checkpoint inhibitors (ICIs) (agents that block programmed cell death protein 1 [PD-1] and programmed cell death protein ligand 1 [PD-L1]) suppress physiologic blocks on immune responses, which can result in autoimmune toxicities, including autoimmune diabetes (incidence approximately #1%).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [216]
ICI-diabetes is an insulin-deficient phenotype that presents as acute severe hyperglycemia or DKA and appears to occur more abruptly than type 1 diabetes.
“ICI-diabetes is an insulin-deficient phenotype that presents as acute severe hyperglycemia or DKA and appears to occur more abruptly than type 1 diabetes (216-218).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [216]
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Cites
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“Future evaluation of this relationship between ICI-DM and antitumor efficacywould be of great interest (15).”
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9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Bajaj, M., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s009 · Cited by 728 · see citing works
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- Authors
- Byun, D. J., Braunstein, R., Flynn, J., Zheng, J., Lefkowitz, R. A., Kanbour, S., & Girotra, M.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Girotra, Monica
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2020-10-13
- Volume
- 43
- Issue
- 12
- Pages
- 3106-3109
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC7770268
- OpenAlex
- W3092474711
- Cited by
- 64
- References
- 3
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 9 · 2023: 14 · 2022: 7 · 2021: 6
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH/NCI Cancer Center Support (P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- immune checkpoint inhibitor toxicity, anti-PD-1 therapy, PD-L1 blockade, diabetic ketoacidosis, GAD65 antibodies, pancreatic atrophy, C-peptide, advanced cancer, immune-related adverse events
- MeSH terms
- Immune Checkpoint Inhibitors, Adult, Aged, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Hyperglycemia, Male, Middle Aged, Neoplasms, Retrospective Studies, Diabetic Ketoacidosis, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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