OBJECTIVEDietary advanced glycation end products (AGEs) and their interactions with the receptor for AGEs (RAGE) may play a role in the pathogenesis of type 1 diabetes. This study set out to assess whether there is any association of circulating concentrations of soluble RAGE (sRAGE), AGEs, and their ratio with the appearance of diabetes-associated autoantibodies in children progressing to clinical diabetes.RESEARCH DESIGN AND METHODSSerum concentrations of sRAGE, N-epsilon(carboxymethyl)lysine (CML) adducts, and the sRAGE/CML ratio were analyzed in children who progressed to type 1 diabetes. The samples were taken at four time points: before seroconversion, at the time of the first autoantibody-positive sample, at the time of the first sample positive for multiple (>2) autoantibodies, and close to the disease diagnosis. Samples of autoantibody-negative controls matched for age, sex, and HLA-conferred diabetes risk were analyzed at corresponding time points.RESULTSThe prediabetic children had higher sRAGE concentrations before seroconversion (P-c = 0.03), at the appearance of multiple autoantibodies (P-c = 0.008), and close to diagnosis (P-c = 0.04). Close to diagnosis, the cases had lower CML concentrations than the controls (P-c = 0.004). Prediabetic children had a higher sRAGE/CML ratio than the controls before seroconversion (P-c = 0.008) and at diagnosis (P-c < 0.001).CONCLUSIONSPrediabetic children have higher concentrations of sRAGE and a higher sRAGE/CML ratio than healthy controls. Circulating sRAGE concentrations seem to decline with the appearance of diabetes-predictive autoantibodies in children progressing to type 1 diabetes. The higher sRAGE/CML ratio in prediabetic children may reflect a higher AGE scavenger capacity.