Lessons from Patients with Anti-Insulin Receptor Autoantibodies

Abstract

Type B insulin resistance is a rare syndrome caused by autoantibodies to the insulin receptor. Patients typically present with severe insulin resistance and hyperglycemia, but some manifest hypoglycemia following a period of hyperglycemia or hypoglycemia alone. The syndrome is predominantly seen in middle-aged black women. Other clinical features of type B insulin resistance are acanthosis nigricans, hyperandrogenism in premenopausal women, autoimmune disorders, proteinuric renal disease, and hematologic abnormalities. In addition to dysglycemia, the metabolic characteristics of the syndrome include low scrum triglyceride levels and high adiponectin levels. The autoantibody acts as an agonist at the insulin receptor at low titers, but functions as an antagonist at high titers. The partial agonist properties of the autoantibody are responsible for the spectrum of glycemic states observed in type B insulin resistance. The treatment of type B insulin resistance has been of limited success to date and protocols addressing multiple components of the underlying autoimmune process arc being developed.