Rapid Onset of Fulminant Type 1 Diabetes 10 Days After the First Dose of Nivolumab: A Case Report

A 70-year-old man was admitted to our hospital for eight days and received treatment with nivolumab, a programmed cell death (PD)-1 inhibitor, for gastric cancer with liver metastasis. On the 10th day after the first administration of nivolumab, he developed symptoms of appetite loss, general malaise, and consciousness disturbance, and he was readmitted to our hospital. Laboratory tests showed ketonuria, metabolic acidosis (pH 6.978; bicarbonate ion level of 1.7 mmol/L), and hyperglycemia (glucose level of 992 mg/dL). His hemoglobin A1c (HbA1c) level was slightly elevated (7.3%), while his HbA1c levels 9 years, 33 days, and 22 days before the administration of nivolumab were 6.0%, 6.1%, and 6.1%, respectively. His serum C-peptide level and 24-hour urinary total C-peptide levels were less than the detection limits. His serum amylase and lipase levels were elevated to more than three times the upper reference limits. He tested negative for islet autoantibodies, including anti-glutamic acid decarboxylase (GAD), anti-insulinoma-associated protein 2 (IA-2), and anti-zinc transporter 8 (ZnT8). The findings in this case indicated that nivolumab caused new-onset fulminant type 1 diabetes (FD). To the best of our knowledge, this case represents the shortest reported time to the development of FD following the first injection of a PD-1 inhibitor. Attention should be paid to the elevation of glucose level even in the very early phase after initial administration of nivolumab.