Immune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes

• Published in: Clinical and experimental immunology Vol. 200; no. 2; pp. 131 - 140
• Main Authors: Quandt, Z., Young, A., Anderson, M.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2020; John Wiley and Sons Inc
• Subjects: Animals; Apoptosis; autoimmune diabetes mellitus; Autoimmune diseases; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - immunology; Cancer immunotherapy; Cell death; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - immunology; Cytotoxicity; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - pathology; Humans; Hyperglycemia; Hypoglycemic Agents - therapeutic use; immune checkpoint inhibitor; Immune checkpoint inhibitors; immune‐related adverse event; Immunotherapy; Insulin; Lymphocytes T; Morbidity; Patients; PD-1 protein; PD-L1 protein; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Review; autoimmune diabetes mellitus; immune checkpoint inhibitor; immune-related adverse event
• ISSN: 0009-9104; 1365-2249; 1365-2249
• DOI: 10.1111/cei.13424

Summary Autoimmune diabetes mellitus is a rare but significant side effect of treatment with immune checkpoint inhibitors. Immune checkpoint inhibitor‐induced diabetes mellitus (CPI‐DM) is characterized by acute onset of dramatic hyperglycemia with severe insulin deficiency and occurrence following exposure to programmed cell death‐1/programmed cell death ligand‐1 (PD‐1/PD‐L1) inhibitors rather than cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) inhibitors. As a growing number of patients undergo immunotherapy, further understanding of the characteristics of CPI‐DM patients is needed for improved prognostic and diagnostic application in order to reduce overall morbidity for this already at‐risk population. Additionally, understanding of the features and mechanisms of CPI‐DM may contribute to understanding mechanisms of spontaneous type I diabetes mellitus (T1DM). Here, we summarize the clinical features of CPI‐DM and interrogate the genetic and cellular mechanisms that may contribute to the disease, as well as the clinical challenges for predicting and treating these patients as increasing cancer immunotherapies reach clinical utility. Immune checkpoint inhibitor‐induced diabetes mellitus (CPI‐DM) is characterized by acute onset of dramatic hyperglycemia with severe insulin deficiency and occurrence following exposure to PD‐1/PD‐L1 inhibitors rather than CTLA‐4 inhibitors. Genetic predisposition is likely to play a role, as is a second trigger. Improved understanding of CPI‐DM is needed clinically to reduce overall morbidity and may also contribute to understanding mechanisms of spontaneous T1DM.