SAT-292 - The Eleven-Day Collapse: Rapid-Onset Autoimmune Diabetes Aftercombined CTLA-4/PD-1 Blockade

Immune checkpoint inhibitors such as ipilimumab (CTLA-4 inhibitor) and nivolumab (PD-1 inhibitor) enhance antitumor immunity but may disrupt self-tolerance, leading to autoimmune toxicities, including type 1 diabetes mellitus (T1DM). While T1DM typically emerges weeks into therapy, we report a hyperacute onset following combined CTLA-4/PD-1 blockade.

A 50-year-old woman with metastatic melanoma presented with 4-5 days of worsening nausea, vomiting, polyuria, polydipsia, and epigastric pain. Two weeks earlier, she received her first cycle of combined ipilimumab and nivolumab. In the ED, she was mildly tachycardic with dry mucous membranes and epigastric tenderness. Initial labs revealed glucose 584 mg/dL, anion gap 24, bicarbonate 13 mmol/L, β-hydroxybutyrate 60.45 mg/dL, lactate 3.6 mmol/L, and venous pH 7.13. Urinalysis showed 4+ glucose and 4+ ketones. She had no personal or family history of diabetes. She was admitted to the ICU for management of diabetic ketoacidosis (DKA) and started on IV fluids and an insulin infusion. CT abdomen/pelvis showed no acute findings. A1c was 5.9% indicating acute onset, with C-peptide of 0.1 ng/mL, negative islet cell antibodies, and >250 IU/mL of glutamic acid decarboxylase (GAD) antibodies confirming autoimmune-mediated T1DM secondary to immune checkpoint inhibitor therapy.

Her acidosis and hyperglycemia gradually improved on insulin drip. Once the anion gap closed, she was transitioned to basal-bolus subcutaneous insulin. Hematology/oncology noted that immunotherapy-associated diabetes is typically irreversible, and she would likely require lifelong insulin. Her abdominal pain and lactic acidosis resolved with supportive care. She remained hemodynamically stable, with no hypoxia or fevers during her hospitalization. She was discharged home on a long-acting and rapid-acting insulin regimen with outpatient endocrinology follow-up for continued management of new-onset immunotherapy-induced T1DM.

This case demonstrates hyperacute immune checkpoint inhibitor–mediated type 1 diabetes mellitus (T1DM), presenting as DKA only 11 days after initiating combined ipilimumab–nivolumab therapy. The patient’s normal A1c and minimal C-peptide reflected abrupt β-cell failure, while markedly elevated anti-GAD65 antibodies confirmed autoimmune etiology. This unusually rapid presentation highlights the potent immune activation associated with dual CTLA-4/PD-1 blockade. Given the severity and likely permanence of ICI-induced T1DM, pre-treatment risk assessment involving potential screening for islet autoantibodies may help identify susceptible patients and enable closer monitoring during early therapy.

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