The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors

• Published in: Acta diabetologica Vol. 56; no. 12; pp. 1239 - 1245
• Main Authors: Marchand, Lucien, Disse, Emmanuel, Dalle, Stéphane, Reffet, Sophie, Vouillarmet, Julien, Fabien, Nicole, Thivolet, Charles, Cugnet-Anceau, Christine
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01.12.2019; Springer Nature B.V
• Subjects: Apoptosis; Autoimmune Diseases - chemically induced; Autoimmune Diseases - epidemiology; Autoimmune Diseases - etiology; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - immunology; Cell Cycle Checkpoints - drug effects; Cell Cycle Checkpoints - immunology; Cell death; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - immunology; CTLA-4 protein; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Lipoatrophic - chemically induced; Diabetes Mellitus, Lipoatrophic - epidemiology; Diabetes Mellitus, Lipoatrophic - immunology; Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 2 - chemically induced; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - immunology; Humans; Immune checkpoint inhibitors; Immunotherapy; Immunotherapy - adverse effects; Insulin; Internal Medicine; Lipoatrophy; Medicine; Medicine & Public Health; Metabolic Diseases; Oncology; Pancreatitis; PD-1 protein; PD-L1 protein; Phenotypes; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Review Article; Anti-PD-1; Diabetes mellitus; Anti-PD-L1; Autoimmune diabetes; Autoimmune generalised lipoatrophy; Beta cell pancreatic function; Autoimmune lipodystrophy; Exocrine pancreatic function; Immunotherapy; Programmed cell death-1 (PD-1); Immune checkpoint inhibitors side effects; Fulminant diabetes; Alpha cell pancreatic function; Programmed death ligand 1 (PD-L1); Pancreas volume; Autoimmune pancreatitis
• ISSN: 0940-5429; 1432-5233; 1432-5233
• DOI: 10.1007/s00592-019-01402-w

Immune checkpoint inhibitors (CPI) are increasingly being used in oncology, and many autoimmune side effects have been described. Diabetes mellitus (DM) has been reported in approximately 1% of subjects treated with programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors, alone or in association with CTLA-4 inhibitors. In the present mini-review, we aimed to describe different clinical pictures and pathophysiology associated with these forms of diabetes. Data on CPI-related DM was gathered from the largest case series in the literature and from our centre dedicated to immunotherapy complications (ImmuCare—Hospices Civils de Lyon). Most cases are acute autoimmune insulin-dependent diabetes which are similar to fulminant diabetes (extremely acute onset with concomitant near-normal HbA1c levels). Other cases, however, have a phenotype close to type 2 diabetes or appear as a decompensation of previously known type 2 diabetes. The occurrence of diabetes can also be a complication of autoimmune pancreatitis induced by CPI use. Finally, two cases of diabetes in a context of autoimmune lipoatrophy have recently been described. Regarding the wide variety of CPI-induced diabetes, the discovery of a glucose disorder under CPI should motivate specialised care for aetiological diagnosis and appropriate treatment.