The relationship between endogenous secretory RAGE and cardiac autonomic function in prediabetes.

Abstract

The putative protective role of esRAGE for cardiac autonomic function (CAF) remains unclear. To address this question, the present study has assessed the relationship of serum AGEs, sRAGE and esRAGE, and tissue AGEs with CAF in a high-risk population without diabetes. This study enrolled 48 subjects of mean age 52.7±11.2years and mean BMI 28.4±6.3kg/m2 , divided into two groups according to glucose tolerance: 16 with normal glucose tolerance (NGT) and 24 with prediabetes. A standard oral glucose tolerance test (OGTT) was performed. The glucose tolerance was defined according to 2006 WHO criteria. Fasting, 120-minutes glucose, lipids, creatinine, and HbA1c were measured. eGFR was calculated (CKD-EPI). Fasting, 120-minutes insulin (ECLIA method), advanced glycation end products (AGEs), plasma-soluble receptor for AGE (sRAGE), and endogenous secreted isoform of the receptor for AGE (esRAGE), (ELISA method) were assessed. HOMA-IR was calculated. Tissue AGEs were assessed by skin autofluorescence (AGE-Reader, DiagnOpticsTM). CAF was evaluated with ANX 3.0 autonomic nervous-monitoring system (ANSAR), applying deep breathing, Valsalva, and standing. There was a significant decline in CAF in prediabetes in comparison with NGT. Serum and tissue AGEs, sRAGE, and esRAGE levels were similar between groups. On the matrix analysis, both sympathetic and parasympathetic activities at baseline and after standing and sympathetic tone during Valsalva were positively related to esRAGE in prediabetes. Multivariate regression analysis showed that esRAGE is an independent contributor to sympathetic, parasympathetic, and total autonomic tone in prediabetes accounting for about 28%, 34%, and 35% of their variances, respectively. Our results have demonstrated that CAF is decreased in prediabetes. esRAGE, but not sRAGE, is reciprocally related to CAF, probably opposing the negative effects of glycation.