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

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.

Automated summary

This study characterized the clinical characteristics and pancreatic volume changes in patients with checkpoint inhibitor-associated autoimmune diabetes (CIADM). It was found that CIADM patients could develop diabetic ketoacidosis and low c-peptide levels within weeks of starting immune checkpoint inhibitor therapy, and their pancreatic volume decreased significantly.