Type B Insulin-resistance Syndromecomplicated With Overlap Syndrome:Diagnosis And Treatment

Background:The type B insulin-resistance syndrome is characterized by the presence of anti-insulin receptor antibodies (AIRA), which cause severe insulin resistance. This syndrome is quite rare, and frequently associated with a history of other autoimmune disease, systemic lupus erythematosus for example. So far, there are less than 100 cases reported in the world, and only 11 cases in China. In contrast with traditional treatment for diabetes, this rare autoimmune disorder has been treated with various forms of immunosuppression with mixed success.Objective:1. To achieve quantitative determination of AIRA by means of enzyme linked immunosorbent assay (ELISA) in one patient suffered from severe insulin resistance and overlap syndrome.2. To discuss the diagnostic and therapeutic strategies of type B insulin resistance syndrome.Methods:1. Quantitative determination of AIRA in the patient’s serum was made before,13days, and 3 months after treatment.2.The therapeutic protocol was made referred to published literature since 1975 when the type B insulin-resistance syndrome was first described. The patient was treated with an intensive combination protocol of corticosteroids (methylprednisolone) and mycophenolate mofetil aimed at control of pathogenic autoantibody production. Blood glucose, glycated hemoglobin, insulin, immunoglobulin, erythrocyte sedimentation rate and rheumatoid associated antibodies were monitored before,13days,49days and 3 months after treatment.3. Systematically analyze the general characteristics, metabolic characteristics, autoimmune characteristics, treatment and prognosis of 11 cases in China.Results:1.The concentration of AIRA in this patient was higher than normal control, and its concentration gradually reduced after application of corticosteroids and immunosuppression agents.2. After treatment, fasting blood sugar dropped to 4-6mmol/L, postprandial blood sugar dropped to 11-15mmol/L, fasting plasma insulin concentration from 424.7μIU/ml down to 194.7μIU/ml and body weight increased by 9kg compared to admission, indicating that the sensitivity to insulin has increased.3. (1) General features:mostly middle-aged women with acanthosis nigricans and hirsutism; (2) Metabolic characteristics:postprandial hyperglycemia, fasting insulin levels often>200μIU/ml, decreased serum albumin, not high triglycerides, normal or reduced white blood cells or platelets, and proteinuria; (3) Immune characteristics: increased erythrocyte sedimentation rate, multiple rheumatoid antibodies such as ANA, Sm, dsDNA, SSA, etc., decreased complement C3 or C4, increased IgG immunoglobulin, and a history of connective tissue disease; (4) Treatment and prognosis:conservative insulin dose used, common protocols being glucocorticoids (prednisone or methylprednisolone) plus immunosuppressive agents (cyclophosphamide mostly),high incidence rate of episodes of hypoglycemia, but no death cases reported.Conclusions:1. Connective tissue disease patients present with severe insulin resistance, type B insulin resistance syndrome should be taken into account.2. Methyl prednisolone plus mycophenolate mofetil protocol is effective for the treatment of type B insulin resistance syndrome.3. After treatment, concentration of AIRA decreased, fasting plasma insulin concentration dropped, and sensitivity to insulin increased.