THU381 A Case of Severe Type B Insulin Resistance Successfully Treated With Combined Immunosuppressive Therapy

Disclosure: A.K. Sumal: None. D.S. Martinez: None. Background: Type B insulin resistance is a rare autoimmune disorder caused by autoantibodies against the insulin receptor and is characterized by markedly high insulin requirements, severe catabolism, and a mortality rate over 50%. Clinical Case: A 50-year-old woman with Sjogren’s syndrome and a one-year history of diabetes treated with insulin presented with diabetic ketoacidosis (DKA) and was found to have type B insulin resistance. Initial laboratory workup demonstrated DKA with a blood glucose of 464 mg/dL (n: 65–99 mg/dL), CO2 8 mmol/L (n: 20–30 mmol/L), anion gap 16 (n: 8–12), pH 7.08 (n: 7.30–7.40) on venous blood gas, 2+ ketonuria, and a hemoglobin A1c of 11.7% (n: <5.7%). Additional workup revealed negative glutamic acid decarboxylase-65, insulin antigen-2, and insulin antibodies, positive C-peptide 2.7 ng/mL (n: 1.1–4.3 ng/mL), and elevated adiponectin 41 ug/mL (n: 5–28 ug/mL). Her physical exam was notable for 100 lb weight loss and extensive acanthosis nigricans, facial acne, and hirsutism. She was started on IV insulin infusion with resolution of her DKA but required more than 5000 units of insulin per day to obtain glycemic control. Due to the suspicion of type B insulin resistance, she was treated with metformin 1000 mg twice daily and pioglitazone 45 mg daily to reverse her hypercatabolic state and combined immunosuppressive therapy consisting of 2 cycles of rituximab 750 mg/m(2) infusion, cyclophosphamide 100 mg daily, and dexamethasone 40 mg for 4 days administered 14 days apart based on a 2018 NIH protocol. Her serum was sent for confirmatory insulin receptor autoantibody testing, which is pending. Over the next 30 days, her insulin requirements improved immensely, and she was ultimately discharged without insulin in clinical remission. To prevent recurrence and hypoglycemia associated with low titers of insulin receptor autoantibodies, she was started on azathioprine 100 mg daily as maintenance therapy. Three months later, she was seen in endocrine clinic in sustained remission with a hemoglobin A1c of 6.0% and resolution of her acanthosis nigricans and hyperandrogenism. Review of her continuous glucose monitor showed no episodes of hypoglycemia. Conclusion: This rare case demonstrates the successful treatment of type B insulin resistance using metformin, pioglitazone, and combination immunosuppressive therapy with rituximab, cyclophosphamide, and pulse-dose steroids, followed by maintenance azathioprine. With a mortality rate over 50%, the use of combined immunosuppressive therapy has transformed this condition into a curable form of diabetes and should be recommended in all patients with type B insulin resistance. Presentation: Thursday, June 15, 2023