Antibodies for ZnT8 is related to age and metabolic status at diagnosis as well as HLA genotype but does not significantly improve the detection rate of β-cell autoimmunity in Finnish children and adolescents affected by T1D.

Age and AGER polymorphisms are associated with the circulating sRAGE concentration among children with type 1 diabetes. The observations of reduced sRAGE concentrations in young children, in those with ketoacidosis, and in carriers of the high-risk HLA DR3/DR4 genotype suggest that decreased sRAGE concentration reflects a more aggressive disease phenotype.

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-«(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.

These data indicate that sRAGE may be involved in the initiation of beta-cell autoimmunity but not in the progression from beta-cell autoimmunity to clinical disease.