Correlation among soluble receptors for advanced glycation end-products, soluble vascular adhesion protein-1/semicarbazide-sensitive amine oxidase (sVAP-1) and cardiometabolic risk markers in apparently healthy adolescents: a cross-sectional study

Abstract

In non-diabetics, low levels of soluble receptor for advanced glycations end products (sRAGE) associate with an increased risk of development of diabetes, cardiovascular afflictions, or death. The majority of studies in non-diabetics report an inverse relationship between measures of obesity, cardiometabolic risk factors and sRAGE and/or endogenous secretory RAGE (esRAGE) levels. To elucidate whether this inconsistency is related to the metabolically healthy obese phenotype, or a different impact of the risk factors in presence and absence of obesity, we analyzed data from 2206 apparently healthy adolescents (51 % girls) aged 15-to-19 years. The association of sRAGE levels with soluble vascular adhesion protein-1/semicarbazide sensitive amine oxidase (sVAP-1/SSAO) was also investigated. Centrally obese, including metabolically healthy, adolescents present significantly lower sRAGE and esRAGE, but not sVAP-1, levels in comparison with their lean counterparts. An increasing number of cardiometabolic risk factors did not associate with significant changes in sRAGE, esRAGE or sVAP-1 levels either in lean or in obese subjects. In multivariate analyses, WHtR, hsCRP, markers of glucose homeostasis, renal function, adiponectin, and sVAP-1 associated significantly with sRAGE and esRAGE. SVAP-1 correlated significantly with glycemia, adiponectin, hsCRP, and sRAGE. Thus, in adolescents, a decline in sRAGE and esRAGE precedes the development of metabolic syndrome. When combined, standard and non-standard cardiometabolic risk factors explain only minor proportion in a variability of sRAGE and esRAGE (8 %-11 %); or sVAP-1 (12 %-20 %). Elucidation of pathogenetic mechanisms underlying early decline in sRAGE and esRAGE levels in obese adolescents and their clinical impact with regard to future cardiometabolic health requires further studies.

Advanced glycation end products and their receptors did not show any association with body mass parameters in metabolically healthy adolescents

“…In this cohort of healthy community‐dwelling adolescents, we did not find any correlation between markers of obesity, such as BMI or waist circumference, and circulating levels of CML or sRAGE, two commonly measured parameters of the AGE‐RAGE axis. This was in contrast to previous studies that showed decreased levels of CML and sRAGE when obese and lean children and adolescents were compared .…”

“…In addition, a study in adolescents showed that soluble receptor for advanced glycation end products (sRAGE) was inversely correlated with the increasing number of components of metabolic syndrome in males but not in females . It has also been reported that a reduction in sRAGE precedes the development of metabolic syndrome . Few studies have been carried out in adolescents, which is a strategically important population, to establish long‐term lifestyle changes aimed at avoiding chronic medical conditions such as diabetes and cardiovascular disease.…”

Gender Differences in Cardiometabolic Risk Factors in Metabolically Healthy Normal Weight Adults with Central Obesity

“…Circulating sRAGE may act as decoy and ameliorate the response towards tissue destruction [33]. Despite that measures of obesity are considered as the most important determinants of low sRAGE levels [34], we did not observe significant betweengroup differences thereof. However, the recent study in healthy women showed that low sRAGE levels reflect accumulation of visceral fat mainly at the epicardial level and are present in advance of metabolic complications [35].…”

Association between metabolically healthy central obesity in women and levels of soluble receptor for advanced glycation end products, soluble vascular adhesion protein-1, and activity of semicarbazide-sensitive amine oxidase

“…Thus, if sRAGE levels mirror tissue RAGE expression, plasma sRAGE should be increased in obesity. In obese pre-pubertal children and adolescents esRAGE-to-sRAGE ratio remains constant (27,28). Thus, endogenous secretory and metalloproteinases-shaded isoforms of sRAGE decline proportionally.…”