(505) Nivolumab/Ipilimumab-Induced Type 1 Diabetes: A Rare but Dangerous Side Effect

Introduction: Immune Checkpoint Inhibitors (ICIs) have become more wildly used due to their ability to boosts a patient’s ability to create an effective immune response to cancer cells. Despite the positive outcomes of the newly developed ICIs, there are immune related adverse reactions affecting several systems including cardiac, dermatological, gastrointestinal, neurological, muscular, pulmonary, and endocrine including ICI induced type 1 diabetes that have not been fully explored.

Description: A 57-year-old male with a medical history of papillary renal cell carcinoma status post right nephrectomy who started his first cycle of Nivolumab/Ipilimumab 16 days prior to coming into the hospital for lethargy and nausea. He was ultimately found to be in diabetic ketoacidosis as evident with a pH of 6.95, beta hydroxybutyrate of 10, lipase over 900, anion gap of 36, and a glucose level of 1686. Further lab work revealed a HgbA1c of 9.8 and a GAD-65 Autoantibody >250 IU/mL. Notably his Hgb A1c 4 months prior to this hospital admission was 5.9 with no previous history of diabetes. He improved with insulin drip and fluids and was discharged on an insulin regimen.

Discussion: While rare, immune checkpoint inhibitor induced type 1 diabetes is a serious side effect with a prevalence up to 2% and most patients developing DKA from ICIs require lifelong insulin. Most endocrinopathies from ICI occur within 12 weeks of starting ICI with no association between the number of treatments and the development of disease as evident with our patient who developed his endocrinopathy after one session. It is thought that blocking PD-1, Immune Checkpoint Inhibitors including Nivolumab allow for increased pancreatic β-cell infiltration and death through activated autoreactive T-cells. While CTLA-4 inhibitors like Ipilimumab alone have less of an association with ICI induced diabetes mellitus compared to PD-1 inhibitors, there is an increased risk of ICI induced type 1 diabetes mellitus when compared to PD-1 inhibitors alone when used in combination as was the case with our patient above.