Abstract

Diabetes mellitus is a group of metabolic disorders of carbohydrate metabolism in which patients develop hyperglycemia. Type 1 diabetes results from cellular-mediated autoimmune destruction of the insulin-producing pancreatic β-cells 1. Patients with type 1 diabetes frequently present with acute symptoms, including life-threatening ketoacidosis, and all patients require lifelong insulin therapy. Type 2 diabetes, which accounts for approximately 90% of all diabetes, has an insidious onset due to combined insulin resistance and insufficient insulin production. In many patients, type 2 diabetes can be controlled with diet, exercise, and oral agents. The worldwide incidence of diabetes has been increasing dramatically. Although most of the rise has been for type 2 diabetes, type 1 has climbed by 2.8% to 4.0% per annum, rising 21% in US youth between 2001 and 2009. At disease onset, most type 1 diabetes patients have autoantibodies to 1 or more of the following: islet cell cytoplasm, insulin [insulin autoantibodies (IAAs)],3 the 65-kDa isoform of glutamic acid decarboxylase (GAD65), insulinoma-associated antigen 2 (IA-2), and zinc transporter 8 (ZnT8) (these are collectively termed islet autoantibodies). Moreover, the presence of islet autoantibodies predicts the development of type 1 diabetes. A recent prospective study measured IAA, GAD65, and IA-2 in 13uu377 children who were at high risk for type 1 diabetes and followed them for 15 years 2. Virtually all the children who had multiple islet autoantibodies developed type 1 diabetes, whereas approximately 15% with a single islet autoantibody progressed to type 1 diabetes. Quantification of islet autoantibodies has proved difficult. Islet cell antibodies were the first autoantibodies identified in type 1 diabetes and are measured on frozen sections of human pancreas by indirect immunofluorescence. The method is technically demanding, labor intensive, difficult to standardize, and currently performed by few laboratories. The other antibodies are most frequently measured by …

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