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Editor’s note: This is one in a series of articles from the various professional section councils of the American Diabetes Association. This installment is from the Council on Complications. The incidence of diabetes, particularly type 2 diabetes, is increasing at an alarming rate. Worldwide, about 124 million people had diabetes by1997; by 2010, this number is estimated to reach 221 million. Because of the large number of severe pathologies complicating the clinical course of diabetes, one can easily speculate on the huge economic and psychosocial impact of diabetes across age groups and geographical regions. A large number of studies have focused on the factors involved in the pathogenesis of diabetic complications, most seeking effective therapies, but the exact cellular or molecular basis of these complications has not yet been fully elucidated. Hyperglycemia is still considered the principal cause of diabetes complications. Its deleterious effects are attributable, among other things, to the formation of sugar-derived substances called advanced glycation end products (AGEs). AGEs form at a constant but slow rate in the normal body, starting in early embryonic development, and accumulate with time. However, their formation is markedly accelerated in diabetes because of the increased availability of glucose. AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and nucleic acids. The initial product of this reaction is called a Schiff base, which spontaneously rearranges itself into an Amadori product, as is the case of the well-known hemoglobin A1c (A1C). These initial reactions are reversible depending on the concentration of the reactants. A lowered glucose concentration will unhook the sugars from the amino groups to which they are attached; conversely, high glucose …