The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors
Résumé
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.
Mots clés
Humans
Anti-PD-1
Anti-PD-L1
Autoimmune diabetes
Exocrine pancreatic function
Fulminant diabetes
Immunotherapy
Immunotherapy/*adverse effects
Pancreas volume
Immune checkpoint inhibitors side effects
*Cell Cycle Checkpoints/drug effects/immunology
Alpha cell pancreatic function
Autoimmune Diseases/chemically induced/epidemiology/etiology
Autoimmune generalised lipoatrophy
Autoimmune lipodystrophy
Autoimmune pancreatitis
B7-H1 Antigen/antagonists & inhibitors/immunology
Beta cell pancreatic function
CTLA-4 Antigen/antagonists & inhibitors/immunology
Diabetes Mellitus
Lipoatrophic/chemically induced/epidemiology/immunology
Type 1/chemically induced/complications/diagnosis/epidemiology
Type 2/*chemically induced/diagnosis/epidemiology/immunology
Programmed cell death-1 (PD-1)
Programmed death ligand 1 (PD-L1)
Protein Kinase Inhibitors/*adverse effects/therapeutic use