SUN-587 - Immune Checkpoint Inhibitor-Induced Autoimmune Diabetes Presenting with Recurrent Diabetic Ketoacidosis

A 79-year-old man with metastatic melanoma on pembrolizumab, coronary artery disease status post coronary artery bypass grafting, hypertension, atrial fibrillation on apixaban, and previously well-controlled type 2 diabetes mellitus on metformin presented after a mechanical fall with generalized weakness and altered mental status. Laboratory evaluation revealed severe hyperglycemia and high anion gap metabolic acidosis consistent with diabetic ketoacidosis (DKA). Notably, he had been discharged four days earlier following an ICU admission for DKA requiring insulin infusion. Despite adherence to a prescribed basal–bolus insulin regimen at home, capillary glucose readings remained persistently elevated.

On admission, laboratory values demonstrated glucose 730 mg/dL, anion gap 39, lactate 13.3 mmol/L, creatinine 3.09 mg/dL, potassium 4.8 mmol/L, and sodium 145 mmol/L. Hemoglobin A1c from the prior admission was 9.3%. Imaging studies, including CT head, were unremarkable for acute pathology. The patient was managed in the intensive care unit with intravenous insulin per DKA protocol. Empiric broad-spectrum antibiotics were initiated for concern of sepsis; however, no infectious source was identified.

Given the abrupt onset of insulin dependence, recurrent DKA, and temporal relationship with pembrolizumab therapy (last infusion August 28; presentation September 21), evaluation for autoimmune diabetes was pursued. Laboratory testing revealed undetectable C-peptide ( < 0.10 ng/mL), markedly elevated GAD-65 antibodies (>250 U/mL), negative IA-2 antibodies ( < 0.4 U/mL), insulin level 10.4 µIU/mL, and low proinsulin ( < 4.0 pmol/L), consistent with autoimmune β-cell failure. Insulinoma was excluded.

Management and Outcome:
Following metabolic stabilization, the patient was transitioned to a revised basal–bolus insulin regimen and discharged with close outpatient endocrinology follow-up. Given the extent of β-cell dysfunction, lifelong insulin therapy was anticipated.

Conclusion
Early recognition of immune checkpoint inhibitor–induced diabetes mellitus is critical to prevent morbidity and recurrent diabetic ketoacidosis. Increased awareness and standardized glucose monitoring protocols are needed for patients receiving immune checkpoint inhibitors to facilitate early diagnosis and timely intervention, thereby reducing hospitalizations and associated healthcare costs.

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