MON-546 - Recognizing Immune-Mediated Diabetes in the Era of Checkpoint Inhibitors: A Case of Nivolumab-Induced DKA

Immune checkpoint inhibitors (ICIs), including the programmed cell death-1 (PD-1) inhibitor Nivolumab, are increasingly used in the treatment of multiple malignancies, including ciliochoroidal melanoma. Despite their therapeutic benefits, ICIs can disrupt immune tolerance by impairing regulatory pathways, leading to immune-related adverse events. ICI-associated diabetes mellitus is an uncommon but potentially life-threatening complication, with an estimated incidence of less than 1%. It is characterized by irreversible pancreatic β-cell destruction, resulting in acute insulin deficiency and severe hyperglycemia. Routine glucose monitoring and prompt recognition of symptoms are critical, as delayed diagnosis may lead to serious complications such as diabetic ketoacidosis (DKA). We present the case of a 73-year-old man with no prior history of diabetes mellitus who developed severe DKA after four cycles of Nivolumab therapy.

73-year-old Hispanic male with a history of right ciliochoroidal melanoma diagnosed in 2021, S/P 4 cycles of Nivolumab, and hypertension presented with generalized weakness, fatigue, and confusion 24 days after his last dose of Nivolumab. He was admitted with severe diabetic ketoacidosis and treated with IV regular insulin, fluids, and potassium replacement. After resolution of hyperglycemia, ketosis, and metabolic acidosis, he was transitioned to subcutaneous insulin and discharged on a basal–bolus insulin regimen. On follow-up, laboratory evaluation showed a hemoglobin A1c of 9.1%, fasting blood glucose of 227 mg/dL, and an undetectable C-peptide level ( < 0.05 ng/mL). Autoimmune testing, including glutamic acid decarboxylase (GAD65), islet antigen-2 (IA-2), and zinc transporter 8 (ZnT8) antibodies, was negative.

According to current ADA recommendations, immune checkpoint inhibitors–associated hyperglycemia can occur at any point during therapy, ranging from days to weeks after the last dose to several months after treatment exposure. Given the potential for abrupt onset and rapid progression, regular glucose monitoring is essential to facilitate early detection and prevent severe metabolic complications such as diabetic ketoacidosis. Initiation of insulin therapy should be promptly considered in patients with significant hyperglycemia, particularly when blood glucose levels exceed 250 mg/dL. Because immune-mediated pancreatic β-cell destruction is typically irreversible, affected patients generally require lifelong insulin therapy.

With the expanding use of immune checkpoint inhibitors, clinicians must remain vigilant for immune-related adverse events, including endocrine complications. Baseline and ongoing monitoring of blood glucose and hemoglobin A1c should be considered and discussed with patients before starting therapy to enable early detection and management of potential endocrine adverse events.

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