• Soichiro Mae, Akira Kuriyama, and Hiromi Tachibana.
• Emergency and Critical Care Center, Kurashiki Central Hospital, Kurashiki, Okayama, Japan.
• J Emerg Med. 2021 Mar 1; 60 (3): 342-344.

BackgroundNivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody with immune checkpoint inhibitory activity, represents a novel treatment for several cancers. Immune checkpoint inhibitors cause side effects, known as immune-related adverse events (irAEs) or delayed immune-related events (DIRE), after immunotherapy discontinuation. Type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis have been reported to develop as an irAE during the treatment with nivolumab. Here, we report on a patient who developed T1DM and diabetic ketoacidosis after discontinuation of treatment with nivolumab as a DIRE.Case ReportA 59-year-old man, who received nivolumab for an alpha fetoprotein-producing gastric cancer, presented with acute fatigue 4 months after discontinuation of nivolumab. Throughout therapy with nivolumab, the patient's hemoglobin A1c (HbA1c) level was ≤ 6%. However, 1 month prior to the patient's emergency department visit, he noticed weight loss, and 3 weeks prior to that, his HbA1c was 7.1%. Urinalysis showed ketone bodies, and arterial blood gas analysis suggested metabolic acidosis with hyperglycemia (690 mg/dL), which established the diagnosis of diabetic ketoacidosis. An endogenous insulin deficiency without verifiable anti-islet autoantibodies was confirmed; the patient had a human leukocyte antigen haplotype that does not increase the risk of acute-onset T1DM. We considered that T1DM in this patient developed possibly due to nivolumab. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the need for clinicians to be vigilant of the fact that a history of anti-PD-1 monoclonal antibody therapy may increase the risk of diabetic ketoacidosis, whether treatment is ongoing or discontinued.Copyright © 2020 Elsevier Inc. All rights reserved.

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