Circulating Concentrations of Soluble Receptor for AGE Are Associated With Age and AGER Gene Polymorphisms in Children With Newly Diagnosed Type 1 Diabetes

Abstract

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.

Decrease in Circulating Concentrations of Soluble Receptors for Advanced Glycation End Products at the Time of Seroconversion to Autoantibody Positivity in Children With Prediabetes

“…Recent studies have shown that events before or at birth are associated with sRAGE concentrations later in life (29,30). Unlike the current study, our previous study on a large population of children with newly diagnosed type 1 diabetes did not show any significant difference in the sRAGE concentrations between cases and healthy controls (14). However, in the previous study, there was a significant difference in the number of children in the diabetic and control groups, and the matching between cases and controls was conducted at the group and not the individual level.…”

“…Similarly, our previous study showed that sRAGE concentrations tend to decline at seroconversion to autoantibody positivity both in an animal model of autoimmune diabetes and in a small group of prediabetic children (10). However, there was no difference in the sRAGE concentrations between newly diagnosed children and adolescents with type 1 diabetes and controls in our recent study (14). These observations created a need for a more specific study of this phenomenon in a larger population of prediabetic children.…”

“…In our previous study, children ,2 years of age had the highest sRAGE concentrations in a series of nondiabetic children aged 0-15 years, although we did not see a linear correlation between age and circulating sRAGE concentrations in that group (14). The number of very young children was small in that population, and the relationship between sRAGE and age seemed to be relatively stable after the age of 5 years (14). The results of the current study and the earlier study suggest that there is a physiological drop in the sRAGE concentration around 2 years of age.…”

“…We have previously identified an association between three polymorphisms of the AGER gene encoding RAGE on a high-risk HLA background (10). We also reported recently in a population-based study that two of the risk-associated AGER polymorphisms also predicted reduced sRAGE concentrations in children with newly diagnosed type 1 diabetes (14).…”

A drop in the circulating concentrations of soluble receptor for advanced glycation end products is associated with seroconversion to autoantibody positivity but not with subsequent progression to clinical disease in children en route to type 1 diabetes

“…Increasing evidence of the involvement of AGEs and sRAGE in the pathogenesis of type 1 diabetes and other autoimmune diseases has been accumulating over recent years . The RAGE/AGE axis is implicated to be a potential therapeutic target for new treatments for metabolic and inflammatory diseases .…”