A Case of Acute-onset Type 1 Diabetes following Nivolumab/Ipilimumab Combination Therapy

We herein report a 67-year-old man with type 1 diabetes mellitus receiving combination immune checkpoint inhibitor (ICI) therapy. He was being treated with nivolumab and ipilimumab for lung metastasis from renal cancer. After one cycle, hyperthyroidism was detected, which evolved into manifest hypothyroidism over the next few weeks, requiring levothyroxine substitution therapy. Eight weeks after initiating ICI therapy, he presented at the emergency department with thirst, weight loss, and generalized weakness. Hyperglycemia (1,234 mg/dL), anion gap metabolic acidosis (pH 7.112), and ketonemia (β -hydroxybutyrate 1,590 μ mol/L) were observed. The glycated hemoglobin level was 9.1 %. Islet-related autoantibodies were all negative. The glucagon tolerance test revealed attenuated secretion of insulin. Human leukocyte antigen was heterozygous for the DRB1＊0405-DQB1＊0401 haplotype. We compared these findings with those of four cases of type 1 diabetes related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy at our institution. All patients showed the DRB1＊0405 or DRB1＊0901 HLA haplotype, which has been shown to be associated with type 1 diabetes in Japan.