Type 1 diabetes induced by immune checkpoint inhibitors

Chin Med J (Engl). 2020 Nov 5;133(21):2595-2598. doi: 10.1097/CM9.0000000000000972.

Abstract

With the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic β cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.

Publication types

  • Review

MeSH terms

  • CTLA-4 Antigen
  • Diabetes Mellitus, Type 1* / chemically induced
  • Humans
  • Immune Checkpoint Inhibitors
  • Immunologic Factors / therapeutic use
  • Immunotherapy / adverse effects
  • Neoplasms* / drug therapy

Substances

  • CTLA-4 Antigen
  • Immune Checkpoint Inhibitors
  • Immunologic Factors