Increased serum concentrations of soluble receptor for advanced glycation endproducts in patients with type 1 diabetes.

To the Editor: The hyperglycemic state occurring in diabetes mellitus is responsible for formation and accumulation of advanced glycation endproducts (AGEs) that participate in the pathogenesis of vascular complications of diabetes mellitus (1). There is considerable interest in the receptors for AGEs (RAGE) found in many cell types, particularly those affected in diabetes. RAGE are members of the immunoglobulin family of cell surface molecules with a diverse repertoire of ligands. Interaction of AGEs with RAGE alters several cell functions through modulation of intracellular signaling, gene expression, and release of proinflammatory molecules and free radicals that contribute to the pathology of diabetic complications (2)(3). A soluble form of RAGE (sRAGE) can be measured in peripheral blood, which could result from the expression of a RAGE splice gene variant that encodes an amino-terminally truncated form of the receptor and/or from the cleavage of the native membranous receptor (4). This form may be released by several cell types, such as endothelial cells and circulating leukocytes. Because sRAGE is presumed to be a decoy for RAGE ligands …