The course of C-peptide levels in patients developing diabetes during anti-PD-1 therapy

Edwin A Basak; Karlijn de Joode; Tom J J Uyl; Ronald van der Wal; Marco W J Schreurs; Sjoerd A A van den Berg; Esther Oomen-de Hoop; Cor H van der Leest; Layal Chaker; Richard A Feelders; Astrid A M van der Veldt; Arjen Joosse; Stijn L W Koolen; Joachim G J V Aerts; Ron H J Mathijssen; Sander Bins

doi:10.1016/j.biopha.2022.113839

The course of C-peptide levels in patients developing diabetes during anti-PD-1 therapy

Biomed Pharmacother. 2022 Dec:156:113839. doi: 10.1016/j.biopha.2022.113839. Epub 2022 Oct 11.

Authors

Edwin A Basak¹, Karlijn de Joode², Tom J J Uyl², Ronald van der Wal³, Marco W J Schreurs⁴, Sjoerd A A van den Berg⁵, Esther Oomen-de Hoop², Cor H van der Leest⁶, Layal Chaker³, Richard A Feelders³, Astrid A M van der Veldt⁷, Arjen Joosse², Stijn L W Koolen⁸, Joachim G J V Aerts⁹, Ron H J Mathijssen², Sander Bins²

Affiliations

¹ Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. Electronic address: e.basak@erasmusmc.nl.
² Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
³ Dept. of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁴ Dept. of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁵ Dept. of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands; Dept. of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁶ Dept. of Pulmonology, Amphia Hospital, Breda, the Netherlands.
⁷ Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Dept. of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁸ Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Dept. of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁹ Dept. of Pulmonology, Erasmus University Medical Center, Rotterdam, the Netherlands.

PMID: 36228374
DOI: 10.1016/j.biopha.2022.113839

Abstract

Introduction: Immune checkpoint inhibitor (ICI) associated diabetes is a harmful adverse event (AE) in patients with cancer following anti-programmed (cell) death protein-1 (PD-1) treatment. There are no available biomarkers able to predict this AE. The primary aim of this study was to investigate C-peptide levels as potential predictor for the occurrence of ICI-related diabetes. The secondary aim was to describe the presence of islet autoantibodies and course of pancreatic enzymes in patients with and without ICI-related diabetes.

Methods: From a total of 1318 patients with cancer who started anti-PD-1 treatment 8 cases and 16 controls were studied in this nested case-control study. C-peptide levels, islet autoantibodies, and pancreatic enzymes were measured in prospectively collected blood serum.

Results: In cases versus controls, median C-peptide levels were comparable at baseline and before toxicity or at the corresponding time point in controls. No patient had C-peptide levels below reference range before toxicity onset. Two out of eight patients in the ICI-related diabetes group had positive islet autoantibodies, whereas one out of 16 patients in the control group had positive islet autoantibodies. Pancreatic enzymes were elevated before diabetes onset in one patient (13%) and in one control (6%) at the corresponding time point.

Conclusions: In patients developing ICI-related diabetes, changes in C-peptide levels, islet autoantibody positivity, and pancreatic enzymes before ICI-related diabetes onset seem comparable to patients without ICI-related diabetes. (NTR: NL6828).

Keywords: C-peptide; Cancer treatment; Immunotherapy; Islet autoantibodies; Pancreatic enzymes.

MeSH terms

Autoantibodies
C-Peptide
Case-Control Studies
Diabetes Mellitus*
Diabetes Mellitus, Type 1*
Humans
Neoplasms*

Substances

C-Peptide
Autoantibodies