Cited by 64Cancer Immunotherapy and BiomarkersDiabetes and associated disordersPancreatic function and diabetes

Immune checkpoint inhibitor-associated diabetes: a single-institution experience

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Byun, David J., Braunstein, Rebecca, Flynn, Jessica, Zheng, Junting, Lefkowitz, Robert A., Kanbour, Sarah, Girotra, Monica·2020·Diabetes Care

Abstract

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%).”
  • 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).”

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Research works printed but not linked: 12

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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
Published
2020-10-13
Volume
43
Issue
12
Pages
3106-3109
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
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
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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