Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors

Diabetes. 2018 Aug;67(8):1471-1480. doi: 10.2337/dbi18-0002. Epub 2018 Jun 24.

Abstract

Insulin-dependent diabetes may occur in patients with cancers who are treated with checkpoint inhibitors (CPIs). We reviewed cases occurring over a 6-year period at two academic institutions and identified 27 patients in whom this developed, or an incidence of 0.9%. The patients had a variety of solid-organ cancers, but all had received either anti-PD-1 or anti-PD-L1 antibodies. Diabetes presented with ketoacidosis in 59%, and 42% had evidence of pancreatitis in the peridiagnosis period. Forty percent had at least one positive autoantibody and 21% had two or more. There was a predominance of HLA-DR4, which was present in 76% of patients. Other immune adverse events were seen in 70%, and endocrine adverse events in 44%. We conclude that autoimmune, insulin-dependent diabetes occurs in close to 1% of patients treated with anti-PD-1 or -PD-L1 CPIs. This syndrome has similarities and differences compared with classic type 1 diabetes. The dominance of HLA-DR4 suggests an opportunity to identify those at highest risk of these complications and to discover insights into the mechanisms of this adverse event.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Autoimmune Diseases / chemically induced*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / physiopathology
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DR4 Antigen / blood
  • HLA-DR4 Antigen / genetics
  • HLA-DR4 Antigen / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / metabolism
  • Insulin / therapeutic use
  • Insulin Secretion
  • Isoantibodies / analysis
  • Ketosis / etiology
  • Ketosis / prevention & control
  • Models, Immunological*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Pancreas / drug effects
  • Pancreas / immunology
  • Pancreas / metabolism
  • Pancreatitis / chemically induced*
  • Pancreatitis / immunology
  • Pancreatitis / metabolism
  • Pancreatitis / physiopathology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / metabolism

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • HLA-DR4 Antigen
  • Hypoglycemic Agents
  • Insulin
  • Isoantibodies
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor