SUN-LB024 Elevation in Morning Glucose Level May Be a Signal for the Development of Immune Checkpoint Inhibitor (ICPi) Induced Autoimmune Diabetes Insulin

Abstract

Unleashing the immune system by using immune checkpoint inhibitors (ICPi) has become a powerful tool in treating a broad spectrum of malignancies. However, increasing the immune response through ICPi therapy can also induce immune-related adverse effects (irAEs). Autoimmune diabetes is a significant endocrine irAE that can be induced by ICPi (1). Without early identification and proper management, autoimmune diabetes can be fatal. We analyzed 11 patients treated with anti-PD1 agents either as a single agent or combined with anti-CTLA4 therapy who developed autoimmune diabetes following initiation of anti-PD1 therapy. Among them, 54.5% (6/11) of patients tested positive for GAD65 autoantibodies, and 54.5% (6/11) developed diabetic ketoacidosis. In all 11 patients, C-peptide levels were low in the presence of hyperglycemia. Radiographic evidence of pancreatitis was found in 18.2% (2/11) of these patients. Other irAEs were found in 63.6% (7/11). ICPi-induced thyroiditis was found in 54.5% (6/11), of which 27.3% (3/11) were newly diagnosed with thyroiditis while the remaining 27.3% (3/11) had previous thyroiditis which worsened with the initiation of ICPi therapy. The median morning (6-8 AM window) glucose level was significantly higher (124 mg/dL (range 101-156)) 2 weeks before onset of autoimmune diabetes than that (99 mg/dL (range 88-117) before ICPi treatment. The median time from ICPi treatment to the onset of autoimmune diabetes was 25 weeks, and median time from thyroiditis to the onset of autoimmune diabetes was 10 weeks. Our data show that morning glucose levels 2 weeks before the onset of autoimmune diabetes increased significantly compared to the baseline morning glucose level prior to ICPi-treatment, suggesting that a significant increase in AM glucose level may predict the development of autoimmune diabetes. Our data suggest that morning glucose may be used as a biomarker to predict onset of autoimmune diabetes in patients treated with anti-PD1 agents.