The relationship between endogenous secretory RAGE and cardiac autonomic
function in prediabetes
Abstract
Aims: The putative protective role of esRAGE for cardiac autonomic
function (CAF) remain 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.
Material and methods: Forty eight subjects of mean age 52.7±11.2years
and mean BMI 28.4±6.3kg/m2, divided into 2 groups according to glucose
tolerance: 16 with normal glucose tolerance (NGT) and 24 with
prediabetes, were enrolled. A standard OGTT was performed. The glucose
tolerance was defined according to 2006 WHO criteria. Fasting, 120-min
glucose, lipids, creatinine and HbA1c were measured. eGFR was calculated
(CKD-EPI). Fasting, 120-min insulin (ECLIA method), esRAGE, sRAGE and
AGEs (ELISA method) were assessed. HOMA-IR was calculated. Tissue AGEs
were assessed by skin autofluorescence (AGE-Reader, DiagnOpticsTM). CAF
was evaluated with ANSAR, applying deep breathing, Valsalva and
standing. Results: There was a significant decline in CAF in prediabetes
in comparison to NGT. Serum and tissue AGEs, sRAGE and esRAGE levels
were similar between groups. On the matrix analysis, both sympathetic
and parasympathetic activity 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. Conclusion: 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.