Distinct changes to pancreatic volume rather than pancreatic autoantibody positivity: Insights into immune checkpoint inhibitors induced diabetes mellitus

Abstract

Background: Immune checkpoint inhibitors (ICI) are promising treatment options for various cancers. However, their use is associated with immune-related adverse events (irAEs), including ICI-induced diabetes mellitus (ICI-DM). This study aimed to investigate the clinical features of ICI-DM, with a particular focus on alterations to pancreatic volume. Methods: We conducted a retrospective review of 2829 patients who received ICI treatment at the Chang Gung Memorial Hospital, Linkou, between January 2014 and December 2021. New-onset diabetes or diabetic ketoacidosis (DKA) was identified in ten patients receiving ICI therapy. Pancreatic volumes were assessed by manual segmentation of computed tomography (CT) images before and after ICI-DM diagnosis. Results: Among these ten patients, nivolumab was the most commonly used ICI (50.0%), followed by pembrolizumab (30.0%) and atezolizumab (20.0%). One patient received combination therapy with nivolumab and ipilimumab. The median age was 63.01 years (range: 40.1 − 87.8). ICI-DM developed after a median of 13.5 cycles (range: 2 − 42) of ICI treatment or 9.85 months (range:1.5 − 21.3) since ICI initiation. The initial presentation was DKA in 60.0% of patients. All patients had low or undetectable C-peptide levels (range: <0.033 − 0.133 nmol/L) and were negative for most type 1 diabetes mellitus (T1DM)-related autoantibodies; only one patient tested positive for glutamic acid decarboxylase antibodies. CT imaging revealed significant pancreatic atrophy, with a median pancreatic volume decrease of 19.92% (P = 0.038) from baseline and sustained significant decline at last follow-up (median − 37.14%, P = 0.012). Conclusions: ICI-DM is often accompanied by pancreatic atrophy and approximately two-thirds of patients initially present with DKA. Although most patients with ICI-DM do not have T1DM-related autoantibodies, awareness of decreased pancreatic volumes with CT imaging is valuable for predicting diabetic emergencies in patients treated with ICIs. Trial registration: This study was approved by the Institutional Review Board of the Chang Gung Memorial Hospital (No.202201766B0).