Monday, August 9, 2010

Treatment of Type B Insulin Resistance: A Novel Approach to Reduce Insulin Receptor Autoantibodies

Treatment of Type B Insulin Resistance: A Novel Approach to Reduce Insulin Receptor Autoantibodies

R. Malek, A. Y. Chong, B. C. Lupsa, A. O. Lungu, E. K. Cochran, M. A. Soos, R. K. Semple, J. E. Balow and P. Gorden

Clinical Endocrine Branch (R.M., A.Y.C., B.C.L., A.O.L., E.K.C., P.G.) and Kidney Diseases Branch (J.E.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Metabolic Research Laboratories (M.A.S., R.K.S.), Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom

Address all correspondence and requests for reprints to: Rana Malek, Building 10-CRC, Room 5-5940, 10 Center Drive, MSC 1453, Bethesda, Maryland 20892. E-mail:

Background: Type B insulin resistance belongs to a class of diseases caused by an autoantibody to a cell surface receptor. Blockade of insulin action results in hyperglycemia, hypercatabolism, severe acanthosis nigricans, and hyperandrogenism in women. This rare autoimmune disorder has been treated with various forms of immunosuppression with mixed success.

Methods: We describe 14 patients with type B insulin resistance referred to the National Institutes of Health, adding to an existing cohort of 24 patients. This report focuses on seven patients who were treated with an intensive combination protocol of rituximab, cyclophosphamide, and pulse corticosteroids aimed at control of pathogenic autoantibody production. Hematological, metabolic, and endocrine parameters, including fasting glucose, glycated hemoglobin, insulin dose, lipids, and testosterone, were monitored before and after treatment.

Results: All seven treated patients achieved remission, defined as amelioration of hyperglycemia, discontinuation of insulin therapy, and resolution of hyperandrogenism. Glycated hemoglobin has normalized in all seven treated patients. Remission was achieved on average in 8 months from initiation of treatment. The medication regimen was well tolerated, with no serious adverse events.

Conclusions: In seven patients with type B insulin resistance, standardized treatment with rituximab, cyclophosphamide, and pulse steroids results in remission of the disease. Future studies will determine whether this treatment protocol can be applied to other autoantibody/cell surface receptor disease states.

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