6588 Insulin Autoimmune Syndrome Presenting with Severe Insulin Resistance and Recurrent Diabetic Ketoacidosis

Abstract Disclosure: E. Looi: None. R. Rosenberg: None. S. Sugar: None. H. Stone: None. A.W. Michels: None. D. Saxon: None. Background: Insulin autoimmune syndrome (IAS) is a rare cause of severe insulin resistance and is typically associated with intermittent hypoglycemia due to insulin antibodies (IA) with high binding capacity and low insulin affinity. However, consideration should be given for atypical presentation of IAS or co-presentation of IAS with type B insulin resistance syndrome (TBIRS) in the absence of hypoglycemia, as described in this case. Case: A 78-year-old African American female (BMI 21 kg/m2) with poorly controlled type 2 diabetes (A1c 11%) experienced recurrent episodes of diabetic ketoacidosis (DKA) despite adherence to escalating insulin doses (310 units daily, 5 u/kg/day). She was referred to endocrinology and continuous glucose monitoring revealed consistently elevated glucose levels (300-400 mg/dL) without hypoglycemia. She had normal renal function, hepatic function, and lipid panel. During a subsequent hospitalization, she required insulin drip rates of 50-70 u/hr. Insulin resistance workup revealed significantly elevated IA level (8.346, normal ≤ 0.010) measured using a fluid-phase radiobinding assay with high insulin binding capacity (1040 U insulin-binding/L blood) and low insulin binding affinity (1.9x107 M), which supported the diagnosis of IAS. Rheumatologic workup for other autoimmune diseases was negative. Due to recurrent DKA episodes, severe insulin resistance without obvious alternative cause, and lack of hypoglycemic events despite low IA binding affinity, co-morbid TBIRS was considered. As there are no commercially available insulin receptor antibody (IRAb) assays, diagnosis could not be confirmed before her condition worsened, and she was admitted for another episode of DKA within a week of being discharged. Due to clinical deterioration and high suspicion for IAS ± TBIRS, treatment with a combination of immunosuppressive agents was initiated in accordance with an NIH protocol (Klubo-Gwiezdzinska J, et al. 2018). Intravenous immune globulin (0.5g/kg/day) was administered over 2 days which resulted in a brief reprieve and followed by significant relapse. Two doses of rituximab (750 mg/m2) and 2 steroid pulses (dexamethasone 40 mg PO daily for 4 days) were then administered 2 weeks apart. Cyclophosphamide 100 mg daily was also started. Her hyperglycemia and insulin requirements subsequently improved, and she was eventually discharged with good glycemic control on a total daily dose of 40 units of insulin (0.5 u/kg/day), an 87.1% reduction in daily insulin requirement. Conclusion: This case demonstrates that IAS - although classically associated with hypoglycemic episodes - may also present with severe insulin resistance and recurrent DKA without hypoglycemia. Whether characterized by high IA binding capacity and affinity or coexisting with IRAb, a combination of immunosuppressants proved effective in treating both TBIRS and IAS in this instance. Presentation: 6/3/2024