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The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors

Lucien Marchand1, Emmanuel Disse2,3, Stéphane Dalle4,5

  • 1Department of Endocrinology and Diabetes, St. Joseph - St. Luc Hospital, Quai Claude Bernard, 69007, Lyon, France. lmarchand@ch-stjoseph-stluc-lyon.fr.

Acta Diabetologica
|August 20, 2019
PubMed

Insights

Immune checkpoint inhibitors (CPI) can cause diabetes mellitus (DM). This review details various presentations of CPI-induced diabetes, from acute insulin-dependent forms to type 2 diabetes phenotypes, emphasizing the need for specialized care.

Area of Science:

  • Oncology
  • Immunology
  • Endocrinology

Background:

  • Immune checkpoint inhibitors (CPI) are widely used in cancer therapy.
  • Autoimmune side effects are known complications of CPI treatment.
  • Diabetes mellitus (DM) is an emerging autoimmune side effect associated with CPI.

Purpose of the Study:

  • To review the clinical presentations and pathophysiology of diabetes mellitus induced by CPI.
  • To consolidate data from extensive case series and a specialized immunotherapy complication center.
  • To highlight the diverse etiological pathways and clinical manifestations of CPI-related DM.

Main Methods:

  • Literature review of case series on CPI-related diabetes.
  • Analysis of data from a dedicated center for immunotherapy complications (ImmuCare-Hospices Civils de Lyon).
  • Description of clinical phenotypes and associated pathophysiological mechanisms.

Main Results:

  • CPI-induced DM occurs in approximately 1% of patients treated with PD-1/PD-L1 or CTLA-4 inhibitors.
  • Common presentations include acute autoimmune insulin-dependent diabetes, resembling fulminant diabetes.
  • Other phenotypes mimic type 2 diabetes, decompensate existing type 2 diabetes, or arise from CPI-induced autoimmune pancreatitis or lipoatrophy.

Conclusions:

  • CPI can induce a spectrum of diabetes mellitus, varying in onset and presentation.
  • Prompt diagnosis and specialized management are crucial for glucose disorders emerging during CPI therapy.
  • Understanding the diverse mechanisms of CPI-induced diabetes is essential for effective patient care.
Keywords:
Alpha cell pancreatic functionAnti-PD-1Anti-PD-L1Autoimmune diabetesAutoimmune generalised lipoatrophyAutoimmune lipodystrophyAutoimmune pancreatitisBeta cell pancreatic functionDiabetes mellitusExocrine pancreatic functionFulminant diabetesImmune checkpoint inhibitors side effectsImmunotherapyPancreas volumeProgrammed cell death-1 (PD-1)Programmed death ligand 1 (PD-L1)

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