Checkpoint inhibitor associated autoimmune diabetes mellitus is characterised by C-peptide loss and pancreatic atrophy

J Clin Endocrinol Metab. 2023 Nov 24:dgad685. doi: 10.1210/clinem/dgad685. Online ahead of print.

Abstract

Objective: To conduct a multi-centre case series characterising 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: i) previous immune checkpoint inhibitor (ICI) therapy; ii) new onset hyperglycaemia (BGL>=11.1mmol/L and/or HbA1c >= 6.5%); and iii) insulin deficiency (C-peptide <0.4nmol/L or diabetic ketoacidosis (DKA)) within 1 month of presentation. Pancreatic volume was available and measured using CT 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-PD1 or anti-PD-L1 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 (T1D) 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 to controls, and demonstrated a mean decline of 41% from pre-treatment to 6 months post CIADM diagnosis.

Conclusions: 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: Checkpoint inhibitors; autoimmune diabetes; diabetes; immune related adverse events; type 1 diabetes.