MON-124 Antibody-Mediated Extreme Insulin Resistance: The Importance of Pre-Treatment Screening

Background: Antibody-mediated extreme insulin resistance is characterized by hyperglycemia despite the use of >200 units of insulin/day and is often divided into two subtypes, insulin receptor antibody-mediated (Type B insulin resistance) and insulin antibody-mediated insulin resistance. The National Institutes of Health (NIH) published an immunomodulatory protocol for the treatment of Type B insulin resistance (1). However, there is scarce data on immunomodulatory therapy use for insulin antibody-mediated insulin resistance, and little has been documented to guide pretreatment screening. Clinical Case: We report the case of a 56 year-old Hispanic male with a 10-year history of well-controlled type 2 diabetes, who presented with abrupt onset hyperglycemia/diabetic ketoacidosis resistant to escalating doses of intravenous insulin infusion (>2500 units daily). He was diagnosed with antibody-mediated insulin resistance due to hyperglycemia requiring very high doses of insulin, lack of identifiable precipitants for diabetic ketoacidosis or hyperosmolar hyperglycemic state, and elevated insulin antibody levels. He underwent pre-immunomodulatory therapy screening for infections, rheumatologic disorders, and malignancy, which uncovered a new diagnosis of latent tuberculosis. He was started on treatment for latent tuberculosis, and began immunomodulatory therapy using the protocol developed by the NIH with rituximab, dexamethasone, and cyclophosphamide. One month after the second therapy cycle, insulin was no longer required for glycemic control, and he maintained appropriate glycemic control on oral diabetic agents alone (metformin and pioglitazone). Conclusion: This case validates the use of immunomodulatory therapy for the treatment of insulin antibody-mediated insulin resistance. It also highlights the importance of pre-immunomodulatory therapy screening to uncover occult infection prior to immunosuppression, and to investigate for possible causal neoplastic or rheumatologic disease. We propose an algorithm for pre-immunomodulatory screening prior to therapy in patients with antibody-mediated insulin resistance. Reference: (1) Malek R, Chong AY, Lupsa BC, et al. Treatment of Type B insulin resistance: a novel approach to reduce insulin receptor autoantibodies. The Journal of Clinical Endocrinology & Metabolism. 2010;95(8):3641-3647.