SUN-685 Approach to a Potential Liver Transplant Candidate with Insulin Antibody-Mediated Severe Insulin Resistance

Introduction: Insulin antibody (IA)-mediated insulin resistance is a rare autoimmune condition resulting in uncontrolled hyperglycemia. High titers of IA are associated with increased mortality secondary to severe insulin resistance and labile blood sugars. There is a paucity of standardized treatment for these patients. Although there have been reported cases of success with immunosuppressants, none of these cases involved patients with liver cirrhosis. We present a case of IA-mediated severe insulin resistance which resulted in uncontrolled hyperglycemia and ultimately delayed liver transplantation. Clinical Case: A 61-year-old male with IA-positive type 2 diabetes, decompensated hepatitis B and NASH cirrhosis presented with several episodes of diabetic ketoacidosis (DKA) and worsening insulin resistance. His liver transplant listing had been placed on hold until glycemic control is achieved. The patient was diagnosed with type 2 diabetes mellitus in 1998. He has no prior autoimmune history. His disease was controlled on Levemir 100 units daily until March 2019 when he presented with his first episode of DKA. He subsequently required 200 units of insulin degludec daily and U-500 insulin 200 units with meals. The patient was readmitted to our hospital in August 2019 for a variceal bleed. His hospital course was complicated by a second occurrence of DKA requiring 100-150 units/hour on an insulin drip for resolution. Labs were significant for HbA1c 8.7% and IA >625 uU/mL (negative if <5.0 uU/mL). He required increasing amounts of basal and prandial insulin after discharge. The patient was again admitted within two months for abdominal pain concerning for spontaneous bacterial peritonitis, which was complicated by his third episode of DKA. Glucoses remained uncontrolled in the range of 170 to 300 mg/dL despite high insulin doses upon discharge. Metformin was contraindicated due to episode of lactic acidosis in the setting of his cirrhosis and concern for repeated episodes of DKA prevented use of SGLT-2 inhibitors. Extensive multidisciplinary discussions led to the decision for an upcoming trial of mycophenolate mofetil followed by plasmapheresis. The goal is to improve glycemic control while also minimizing infection risk to ultimately list him for a liver transplant. Conclusion: This patient highlights a major therapeutic challenge related to uncontrolled hyperglycemia and insulin resistance from anti-insulin antibodies in a cirrhotic patient. This can place patients at high risk for infection, poor wound healing and most importantly prohibit liver transplantation. Immunosuppressant therapy and plasmapheresis may drastically lower insulin antibodies and improve glycemic control, however, it will increase the risk of infection.