A51-50 Diagnosis and Management of Type B Insulin Resistance Syndrome in the Intensive Care Setting

Introduction Autoantibodies against insulin receptors represent a rare cause of severe insulin resistance. These antibodies block insulin signaling and cause marked hyperglycemia through severe insulin resistance. The presence of anti-insulin receptor antibody adds an additional layer to the glycemic instability separate from the autoimmune destruction of beta cells seen in type 1 diabetes mellitus. This is commonly referred to as type B insulin resistance syndrome (TBIRS). Below, we present the case of a 77-year-old female with type 1 diabetes admitted for diabetic ketoacidosis (DKA), driven by high levels of anti-insulin receptor antibodies. Case Description Prior to hospitalization, the patient was taking 20 units of insulin glargine daily and 30 units of insulin lispro with meals. After a COVID-19 infection in 2024, she developed severe insulin resistance, requiring glargine 200 units/day and lispro 100 units/meal. She eventually presented to her local emergency department with nausea and vomiting and was found to be in diabetic ketoacidosis. Blood glucose readings remained in 300s-400s mg/dL with an elevated anion gap despite increasing the insulin drip to as high as 30 units/h. Subcutaneous insulin NPH 15 units twice daily was added in adjunct to insulin drip without improvement. Endocrinology was consulted, and workup for autoimmune etiology was initiated. Empiric prednisone was initiated leading to improved glucose control while awaiting insulin receptor antibody test results. Anti-insulin receptor antibody ultimately returned positive. Eventually, DKA resolved with continued fluid resuscitation and steroid therapy. The patient was discharged on prednisone and insulin regular U-500 75 units with meals. In the outpatient setting, prednisone was weaned off, with blood glucose remaining well controlled on U-100 insulin lispro with meals. Discussion Differentiating the etiology of DKA caused by TBIRS from poor medication adherence can be difficult in the early stages of treatment. DKA arising from poor medication adherence typically stabilizes with adequate fluid resuscitation and intravenous insulin administration. TBIRS should be considered in patients with rapidly rising insulin needs or altered insulin requirements after immune triggers such as a viral illness or development of a new autoimmune condition. The role of autoimmunity in DKA should be considered in critically ill patients who have been adherent to outpatient insulin therapy and lack other clear provoking factors. In this patient population, we recommend early engagement with Endocrinology for assistance with hyperglycemia management and consideration of glucocorticoid therapy.