A Case of Nivolumab-Induced Fulminant Type 1 Diabetes with Steroidsand Glucagon-Like Peptide 1 Administration during the Early Onset

Background: Nivolumab is a humanized IgG4 anti-programmed cell death protein-1 (PD-1) antibody. In recent years, type 1 diabetes associated with anti-PD-1 immunotherapy has been reported. Case report: We report a 62-year-old woman with primary choroidal melanoma who developed fulminant type 1 diabetes after anti-PD-1 immunotherapy (nivolumab). She had elevated levels of blood glucose and total blood ketone body. Her hemoglobin A1c level was at the upper limit of normal, and she had decreased endogenous insulin secretion. Anti-glutamic acid decarboxylase and anti-islet antigen 2 antibody tests were negative. Endogenous insulin was still being secreted at the time of diagnosis; therefore, we administered steroids and glucagon-like peptide-1 (GLP-1). However, insulin secretion did not recover. Approximately 10 months after onset, her diabetes was under control with intensive insulin therapy and voglibose treatment. Discussion: The mechanism of diabetes caused by nivolumab is unclear, but it may involve the excessive autoimmune response associated with PD-1 inhibition. GLP-1 has a protective effect on the pancreas by promoting differentiation and proliferation of pancreatic β cells and suppressing pancreatic β cell apoptosis. We attempted to treat with steroids and GLP-1 before depletion of endogenous insulin to suppress the hyperimmunization and protect the pancreatic β cells. Insulin secretion did not recover. However, no reports have described using these therapies to treat diabetes associated with immune checkpoint inhibitors during early onset to date. We consider this case is the meaningful report as a negative data.