Decrease in circulating concentrations of soluble receptors for advanced glycation end products at the time of seroconversion to autoantibody positivity in children with prediabetes.

Abstract

OBJECTIVE:

Dietary 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 METHODS:

Serum concentrations of sRAGE, N-ε(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.

RESULTS:

The prediabetic children had higher sRAGE concentrations before seroconversion (Pc = 0.03), at the appearance of multiple autoantibodies (Pc = 0.008), and close to diagnosis (Pc = 0.04). Close to diagnosis, the cases had lower CML concentrations than the controls (Pc = 0.004). Prediabetic children had a higher sRAGE/CML ratio than the controls before seroconversion (Pc = 0.008) and at diagnosis (Pc < 0.001).

CONCLUSIONS:

Prediabetic 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.

• Authors: Kirsi M Salonen, Samppa J Ryhänen, Josephine M Forbes, Danielle J Borg, Taina Härkönen, Jorma Ilonen, Olli Simell, Riitta Veijola, Per-Henrik Groop, Mikael Knip
• Journal: Diabetes care (Diabetes Care) Vol. 38 Issue 4 Pg. 665-70 (Apr 2015) ISSN: 1935-5548 [Electronic] United States
• PMID: 25573878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Autoantibodies
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• N(6)-carboxymethyllysine
• Lysine

Topics

• Autoantibodies (blood)
• Case-Control Studies
• Child
• Child, Preschool
• Diabetes Mellitus, Type 1 (blood, epidemiology)
• Disease Progression
• Down-Regulation
• Female
• Humans
• Infant
• Infant, Newborn
• Lysine (analogs & derivatives, blood)
• Male
• Prediabetic State (blood, epidemiology, pathology)
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (blood)