Checkpoint Inhibitor-Associated Autoimmune Diabetes Mellitus Is Characterized by C-peptide Loss and Pancreatic Atrophy

J Clin Endocrinol Metab. 2024 Apr 19;109(5):1301-1307. doi: 10.1210/clinem/dgad685.


Objective: To conduct a multicenter case series characterizing the clinical characteristics at presentation and pancreatic volume changes of patients with checkpoint inhibitor-associated autoimmune diabetes (CIADM).

Research design and methods: Electronic medical records were reviewed with 36 consecutive patients identified with CIADM, as defined by (1) previous immune checkpoint inhibitor (ICI) therapy, (2) new-onset hyperglycemia (blood glucose level ≥ 11.1 mmol/L and/or glycosylated hemoglobin ≥ 6.5%), and (3) insulin deficiency [C-peptide <0.4 nmol/L or diabetic ketoacidosis (DKA)] within 1 month of presentation. Pancreatic volume was available and measured using computed tomography volumetry for 17 patients with CIADM and 3 sets of control patients: 7 with ICI-related pancreatitis, 13 with asymptomatic ICI-related lipase elevation, and 11 ICI-treated controls for comparison.

Results: All patients had either anti-programmed cell death protein 1 or anti-programmed cell death ligand 1 therapy. Median time from ICI commencement to CIADM diagnosis was 15 weeks. At presentation, 25 (69%) had DKA, 27 (84%) had low C-peptide, and, by 1 month, 100% had low C-peptide. Traditional type 1 diabetes autoantibodies were positive in 15/35 (43%). Lipase was elevated in 13/27 (48%) at presentation. In 4 patients with longitudinal lipase testing, elevated levels peaked 1 month prior to CIADM diagnosis. Pancreatic volume was lower pre-ICI in CIADM patients compared with controls and demonstrated a mean decline of 41% from pretreatment to 6 months post-CIADM diagnosis.

Conclusion: Pronounced biochemical and radiologic changes occur during CIADM pathogenesis. Rapid loss of C-peptide is a distinct characteristic that can be used to aid diagnosis as autoantibodies are often negative.

Keywords: autoimmune diabetes; checkpoint inhibitors; diabetes; immune-related adverse events; type 1 diabetes.

Publication types

  • Multicenter Study

MeSH terms

  • Atrophy / chemically induced
  • Autoantibodies
  • C-Peptide
  • Diabetes Mellitus, Type 1* / chemically induced
  • Diabetes Mellitus, Type 1* / drug therapy
  • Diabetic Ketoacidosis*
  • Humans
  • Lipase


  • C-Peptide
  • Autoantibodies
  • Lipase