A Case of Immune Checkpoint Inhibitor Induced Autoimmune Diabetes

Introduction: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block checkpoints such as CTLA-4, PD-1, PDL-1 resulting in an antitumor immune response. ICIs can cause immune-related adverse events such as autoimmune diabetes. Clinical Case: 64 yr old male with history of non-small cell lung cancer (NSCLC) undergoing therapy with carboplatin, taxol, and pembrolizumab (monoclonal PD-1 receptor inhibitor) presented to the ED with weakness and dizziness. Patient reported a 1 week history of polyuria, fatigue, polydipsia, and weakness. He started his cancer treatment 2 months prior to presentation and received a total of 3 cycles with the last cycle being 3 weeks prior to presentation. Patient had no personal or family history of diabetes. On presentation to the ED vitals were: HR 130, RR 40, BP 166/100. Labs were significant for Na 122(135–145 mmol/L), bicarb 5(22–30 mmol/L), creatinine 1.76(0.70–1.30 mg/dl), glucose 1,147(70–179 mg/dl), beta hydroxybutyrate 10(0.02–0.27 mmol/L), anion gap 38(7–15 mmol/L), hemoglobin A1c 7.8%(4.8–5.6%), islet cell ab 0 (<=0.02 nmol/L), GAD65 Ab 0.36 (<=0.02 nmol/L). CT abdomen showed no pancreatic abnormalities. Patient was diagnosed with DKA from autoimmune diabetes induced by pembrolizumab. He was given fluids, started on an insulin drip and admitted to the ICU. He was transitioned off the insulin drip onto basal/basal insulin on discharge. One month post discharge the patient continues to require insulin. Learning points: Although the incidence of autoimmune diabetes mellitus associated with ICIs is only 0.2–0.9%, most of these patients present with severe DKA making this a dangerous adverse event that clinicians should be aware of(1). The patient in this case had symptoms of new onset severe fatigue, polyuria, polydipsia 1 week prior to his presentation to the ED. This case teaches us that patients undergoing therapy with ICIs should be educated about the signs and symptoms of hyperglycemia and DKA, with directions to inform a health care provider should they occur. Potential interventions that will allow us to identify these patients prior to presentation with dangerous DKA include patient self-monitoring of symptoms and blood glucose checks with a glucometer. Reference: Akturk, H. K., Kahramangil, D., Sarwal, A., Hoffecker, L., Murad, M. H., & Michels, A. W. (2019). Immune checkpoint inhibitor-induced Type 1 diabetes: a systematic review and meta-analysis. Diabetic medicine: a journal of the British Diabetic Association, 36(9), 1075–1081. https://doi.org/10.1111/dme.14050