Abstract

Background: Autoimmune Antibodies against insulin receptors leading to refractory hyperglycemia is known as Type B insulin resistance. In addition to insulin management, immunosuppressive therapy appears to be an essential part for successful management. Clinical Case: A 20 year old African American woman with no significant past medical history presented to the Emergency Department with worsening nausea and vomiting for 5 days and shortness of breath. She admitted to polyuria, unintentional weight loss of 15 pounds in the last six months, decreased appetite, and hyper-pigmented rashes mostly on her back. The patient was not on any medications at home. No known drug allergies, no past surgical history. Family history was significant for Grandmother with Type 2 Diabetes Mellitus and Lupus on father’s side of family. The patient denied use of alcohol, tobacco, illicit and IV drug use. T: 37.2 °C, HR: 124, RR: 25, BP: 105/74, SpO2: 100%. Weight 45kg. Physical exam significant for Tachycardia but normal rhythm. Initial work up revealed new onset diabetes HbA1c 9.6% and massive pericardial effusion on echocardiogram s/p pericardiocentesis. Due to developing complaints of intermittent cyanosis of fingertips and intermittent joint pain of fingers, Rheumatology work up was ordered and positive for mixed connective tissue disease. Patient was treated with Cellcept 1500 mg BID, Plaquenil Sulfate 300 mg daily, and prednisone 12.5 mg BID. Hospital course was complicated due to hyperglycemia in 300s-400mg/dL requiring high amounts of insulin. Diabetes work up was negative for GAd-65 and islet cell antibodies. C-peptide was elevated at 16.1 ng/mL (0.8-3.1 ng/mL) and anti-Insulin an antibodies was 20uU/mL. Patient was euthyroid. Hyperglycemia persisted despite increasing doses of long and short acting insulin subcutaneously. The patient eventually required Insulin intravenously at 50 units/hour plus 50 units of short acting Insulin every 4 hours subcutaneously. The patient was transferred to a facility to begin Combined Immunosuppressive Therapy plus insulin to manage hyperglycemia due to insulin resistance. After six months of rituximab, high-dose pulsed steroids, cyclophosphamide, plus insulin therapy, glycemic index improved with HbA1c reduced to 5.6%. Conclusion: Combined Immunosuppressive Therapy in addition to insulin management of refractory hyperglycemia due to type B insulin resistance has been shown to not only be effective in controlling refractory hyperglycemia but preventing against recurrences as well. Reference: 1) Klubo-Gwiezdzinska J, Lange M, Cochran E, Semple RK, Gewert C, Brown RJ, Gorden P. Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study. Diabetes Care. 2018 Nov;41(11):2353-2360.

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