Fulminant onset of insulin-dependent diabetes with positive anti-GAD antibody titers during treatment with nivolumab in a patient with NSCLC

Programmed cell death-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) inhibitors have been highlighted in the field of cancer treatment. The interaction between PD-1 and PD-L1 is thought to play an important role in the regulation of the self-immune tolerance mechanism, so blocking these molecules may cause serious immune-related adverse events (IrAE), including fulminant insulin-dependent (type 1) diabetes. Here, we describe a patient with fulminant type 1 diabetes induced by nivolumab, an anti-PD-1 antibody. The patient, a 78-year-old man, was being treated with nivolumab as a third-line treatment for squamous cell carcinoma of the lung. After three cycles, he experienced an abrupt flare-up of the blood glucose within half a day. His blood glucose further increased without clinical symptoms until his hospital visit. Laboratory data showed the complete exhaustion of intrinsic insulin and the elevation of serum antibody titer to glutamic acid decarboxylase (GAD). Although the patient was previously diagnosed with non-insulin-dependent (type 2) diabetes, his disease activity had been well controlled with oral medication and low-dose insulin therapy until just before the flare-up. Because of the laboratory findings and the extremely rapid onset of hyperglycemia, a diagnosis of fulminant, rather than the rapid onset, type 1 diabetes related to nivolumab therapy was strongly suspected. Our case study indicates that fulminant hyperglycemia can occur extremely rapidly. The blood glucose of patients receiving PD-1 antibody therapy should be closely monitored.