title: Treatment of type B insulin resistance: a novel approach to reduce insulin receptor autoantibodies.
abstract: 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.
authors.affiliation: Clinical Endocrine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10-CRC, Room 5-5940, 10 Center Drive, MSC 1453, Bethesda, Maryland 20892, USA. malekr@niddk.nih.gov
authors.forename: R
authors.initials: R
authors.lastname: Malek
authors.forename: A Y
authors.initials: AY
authors.lastname: Chong
authors.forename: B C
authors.initials: BC
authors.lastname: Lupsa
authors.forename: A O
authors.initials: AO
authors.lastname: Lungu
authors.forename: E K
authors.initials: EK
authors.lastname: Cochran
authors.forename: M A
authors.initials: MA
authors.lastname: Soos
authors.forename: R K
authors.initials: RK
authors.lastname: Semple
authors.forename: J E
authors.initials: JE
authors.lastname: Balow
authors.forename: P
authors.initials: P
authors.lastname: Gorden
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies / Q000276:immunology*; D001786:Blood Glucose / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy / Q000276:immunology; D006943:Hyperglycemia / Q000188:drug therapy* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011972:Receptor, Insulin / Q000276:immunology*; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D001786:Blood Glucose; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D011972:Receptor, Insulin