SUN-170 Development of Type 1 Diabetes Mellitus on Immune Checkpoint Inhibitor

Introduction: Immune checkpoint inhibitors (ICPi) are used to augment the immune response and have led to improved outcomes in various malignancies. With this enhanced immunologic response comes a spectrum of side effects, known as immune-related adverse events (iRAEs). These are most commonly dermatologic, gastrointestinal, and endocrine-related events, with development of autoimmune diabetes occurring in only 0.2% of all reported iRAEs. Case: A 61-year-old male with pre-diabetes and metastatic small cell lung cancer post chemotherapy previously on combination ICPi, nivolumab and ipilimumab, presented with worsening nausea, vomiting, and decreased oral intake. He received 4 doses of combined therapy, developed presumed secondary adrenal insufficiency, and was switched to ipilimumab monotherapy for 10 doses. He started to have hyperglycemia within the first month of being on monotherapy. Despite discontinuation of ipilimumab 2 months prior to presentation, he had progressive hyperglycemia, which was poorly controlled with glipizide. At initial presentation, laboratory findings revealed diabetic ketoacidosis (DKA). He was managed on an insulin drip with resolution within 24 hrs. Workup showed a hemoglobin A1c of 7.9%, undetectable c-peptide level and negative autoimmune diabetes antibodies. He was diagnosed with new onset type 1 diabetes (T1DM) and was discharged on basal-bolus insulin. Discussion: The most common adverse events with ICPi use are diarrhea, fatigue, pruritus, and rash. While the most common endocrinopathies reported are thyroid dysfunction and hypophysitis, providers should also be aware of the serious but rarer iRAEs of autoimmune adrenalitis and autoimmune diabetes. All but one reported case is associated with the use of PD-1 inhibitor monotherapy or combination therapy with CTLA-4 inhibitor. According to a recent meta-analysis, around 85.7% of cases presented in DKA within 1 to 52 weeks following ICPi initiation and, like our patient, usually have mildly elevated hemoglobin A1c’s and low levels of c-peptide. Individuals with T1DM can express any combination of islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase (GAD), antibodies to tyrosine phosphatase-like proteins (IA-2, ICA512), and antibodies to zinc transporter 8 (ZnT8). No dominant pattern of antibody production is observed in the reported cases of ICPi-associated T1DM. Although these antibodies can help in diagnosing T1DM, more than 25% lack such autoantibodies and are still classified as having T1DM, as seen in this case. Conclusion: ICPi can potentially prolong survival for many cancer patients with an otherwise grim prognosis. As ICPi use is expected to expand in the coming years, it is especially important to study and report less common iRAEs to better understand, recognize, and manage these potentially serious adverse effects.