Introduction and Objective: Immune checkpoint inhibitors (ICIs), including pembrolizumab, have transformed cancer therapy but are associated with immune-related adverse events, including endocrinopathies. Immune checkpoint inhibitor-induced diabetes mellitus is a rare but potentially life-threatening complication characterized by abrupt insulin deficiency and frequent presentation with diabetic ketoacidosis. We report a case of pembrolizumab-associated autoimmune diabetes presenting with recurrent diabetic ketoacidosis to highlight the importance of early recognition. Methods: Clinical data were obtained through retrospective review of the patient’s electronic medical record. Results: A 79 year old male with metastatic melanoma on pembrolizumab presented with recurrent diabetic ketoacidosis despite recent initiation of basal-bolus insulin therapy. Laboratory evaluation revealed severe hyperglycemia, high anion gap metabolic acidosis, elevated lactate, and acute kidney injury. HgbA1c obtained during a hospitalization four days earlier was 9.3%.The patient had previously been on Metformin for Type 2 diabetes for several years. Given the abrupt onset of insulin dependence, autoimmune diabetes was suspected. Testing demonstrated undetectable C-peptide and markedly elevated GAD-65 antibodies, with negative IA-2 antibodies, normal insulin level, and low proinsulin, consistent with immune-mediated B cell destruction. The patient was diagnosed with immune checkpoint inhibitor-induced autoimmune diabetes and transitioned to a revised basal-bolus insulin regimen prior to discharge. Conclusion: Immune checkpoint inhibitor-induced autoimmune diabetes can present abruptly with severe insulin deficiency and recurrent diabetic ketoacidosis. Early recognition is critical, as B-cell failure is often rapid and irreversible. Routine glucose monitoring and heightened clinical awareness in patients receiving immune checkpoint inhibitors may prevent severe metabolic complications. Disclosure S. Sharma: None. M. Ramakrishna Reddy: None. R. Gopavaram: None. A. Mazhar: None.
Sharma et al. (Fri,) studied this question.