Background: Immune mediated diabetes mellitus (DM) is a rare complication of immune checkpoint inhibitor (ICI) therapy, with an incidence of less than 1%. We present a case of immune-mediated DM with nivolumab therapy presenting as diabetic ketoacidosis (DKA).

Case: A 74-year-old Caucasian male with no history of DM or autoimmune disease was diagnosed with stage III metastatic melanoma and started on treatment with nivolumab, an ICI. He tolerated treatment well and had no evidence of endocrine dysfunction on routine laboratory monitoring. Shortly after completing his 14th cycle of nivolumab therapy, he presented to the emergency department with a one-week history of fatigue, poor appetite, polydipsia, and polyuria. He was found to have DKA with serum blood glucose 446 mg/dL, anion gap 20 mEq/L, serum bicarbonate 14 mEq/L, arterial pH 7.23, and 4+ urine ketones. His hemoglobin A1c was 7.3%, increased from 5.4% one year earlier. He was treated with intravenous insulin then transitioned to basal-bolus subcutaneous insulin therapy, which was continued at discharge. Evaluation in the outpatient setting revealed no measurable GAD65 antibodies or anti-insulin antibodies, but his serum c-peptide was found to be <0.10 ng/mL with corresponding serum blood glucose level 214 mg/dl. This supported a diagnosis of endocrine pancreatic insufficiency, in his case likely immune mediated due to nivolumab therapy. He completed an additional 6 cycles of nivolumab with no further complications. Meanwhile his DM became well-controlled with subcutaneous insulin injections, and he was eventually transitioned to insulin pump therapy.

Discussion: ICIs such as nivolumab are known to cause multiple autoimmune complications that can appear at any point during treatment. The underlying mechanisms of beta cell immunotoxicity are incompletely understood, but progression to insulin-dependency appears to be rapid. It is important to recognize new or worsening DM early to avoid life-threatening complications such as DKA.


S.M.Iqbal: None. C.Houston: None.

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