(281) How Much Insulin?! Challenges of Type B Insulin Resistance

Introduction: Type B insulin resistance is a rare, autoimmune disorder marked by autoantibodies against the insulin receptor.This acquired condition impacts middle-aged and older adults and often accompanies other autoimmune diseases, like systemic lupus erythematosus and rheumatoid arthritis, suggesting a shared underlying immune dysfunction. These autoantibodies disrupt insulin receptor function, causing severe insulin resistance, and complicating treatment due to the necessity of high insulin doses.

Description: A 33-year-old male with no known past medical history presented with hematuria, fatigue, polyuria, and polydipsia for one week. Initial tests showed leukopenia, thrombocytopenia, glucose of 473 mg/dL, anion gap 13, beta hydroxybutyrate 3.49 mmol/L, and HgbA1C 8.6%. He was hemodynamically stable, diagnosed with diabetes mellitus without diabetic ketoacidosis (DKA), and started on subcutaneous insulin. On hospital day 3, he entered DKA, and an insulin drip was initiated on top of subcutaneous insulin and escalated to 70 units/hour without resolution. This lack of response suggested Type B insulin resistance.

Type B insulin resistance was confirmed with a renal biopsy, revealing lupus nephritis. An immunosuppressive regimen, including dexamethasone, cyclophosphamide, rituximab, and plasmapheresis was started with National Institute of Health guidance. The patient required up to 227,600 units/day of insulin, consisting of U-100 infusions and U-500 subcutaneous doses. These high doses created challenges in formulation, supply chain, and administration that required multi-disciplinary collaboration among clinicians, pharmacists, and ICU nursing staff. The patient had a prolonged ICU stay and was eventually discharged home on hospital day 81 with plans for readmission for further steroid and plasmapheresis treatments.

Discussion: Diagnosing Type B insulin resistance demands a high index of suspicion and specialized testing, typically revealing elevated insulin levels despite hyperglycemia, and confirmed by presence of anti-insulin receptor antibodies. Treatment involves a combination of immunosuppressive agents and high-concentration insulin infusions, posing safety, access, and formulation concerns, and requiring ICU administration for close monitoring.