Nivolumab-induced type 1 diabetes mellitus as an immune-related adverse event

Immune checkpoint inhibitors are medications that activate anti-tumor responses by disrupting the inhibitory signaling to T cells. Nivolumab is an immune checkpoint inhibitor that selectively blocks the programmed cell death-1 (PD-1). Anti-PD-1 agents can breach immunologic tolerance. Fulminant diabetes is an immune endocrinopathy that results from a violent immune attack leading to complete destruction of pancreatic beta cells. We present a rare case of fulminant diabetes precipitated by anti-PD-1 immunotherapy.

A 49-year-old male with a body mass index of 26.4 kg/m², a history of Dandy-Walker syndrome and epilepsy, and no personal or family history of diabetes underwent left radical nephrectomy and retroperitoneal lymph node dissection for stage IV metastatic renal cell carcinoma (metastases to lungs). He received first-line sunitinib treatment for three months. He developed new hepatic metastasis, and a second-line treatment with nivolumab 3 mg/kg every two weeks was introduced. At 10 months of nivolumab, before the 22nd infusion, the patient suddenly complained of severe asthenia, somnolence, weight loss, polydipsia, and polyuria. Laboratory tests revealed potassium 4.2 mmol/L, sodium 138 mmol/L, bicarbonate 17.8 mmol/L, blood glucose 801 mg/dL, and arterial blood pH 7.27. He was diagnosed with diabetic ketoacidosis. Hemoglobin A1C was 10.9%. C-peptide was so low as 0.24. Glutamic acid decarboxylase autoantibodies, insulin autoantibodies and islet cell antibodies were all negative.

Anti-PD-1 immunotherapy is effective in the treatment of cancers. These agents can precipitate autoimmune disorders. As the use of anti-PD-1 agents is expected to rise, physicians should be educated about the potential side effects.