Racial differences in circulating levels of the soluble receptor for advanced glycation endproducts in middle-aged and older adults

Abstract

Background Low levels of the soluble receptor for advanced glycation endproducts (sRAGE) have been implicated in a number of chronic diseases. Previous studies indicate that sRAGE levels are ~30% lower in Blacks compared to Whites. However, the reasons for these differences are unclear. Purpose We aimed to identify predictors of circulating sRAGE biomarkers among Black and White adults at high cardiac risk. Methods Serum levels of total sRAGE, endogenous secretory RAGE (esRAGE), carboxymethyl-lysine (CML, a major RAGE ligand), and their ratios were measured in 99 Blacks and 454 Whites. Results Blacks had a more adverse cardiovascular risk profile, as well as lower median levels of total sRAGE (972 vs. 1564 pg/ml) and esRAGE (474 vs. 710 pg/ml) compared to Whites (p<0.0001). In addition, the proportion of esRAGE was higher in Blacks (47% vs. 44%, p=0.02), as were the CML/total sRAGE (0.89 vs. 0.56 ng/pg) and CML/esRAGE (1.72 vs. 1.20 ng/pg) ratios (p<0.0001). Racial differences persisted after adjustment for key covariates including age, gender, tobacco use, comorbidities, BMI, blood pressure, glucose, insulin, triglycerides, C-reactive protein, and renal function (p<0.05). Race alone accounted for nearly half of the variability in total sRAGE levels (10.6%; model explained 23.9%). In stratified analyses, gender and heart rate were independently associated with total sRAGE and esRAGE in Whites, while CML and C-reactive protein were associated with total sRAGE in Blacks. Conclusions We identified several independent predictors of sRAGE biomarkers. Notably, Black race was associated with an adverse AGE/RAGE profile, including lower sRAGE and higher CML/sRAGE ratios.

Circulating Levels of the Soluble Receptor for AGE (sRAGE) during Escalating Oral Glucose Dosages and Corresponding Isoglycaemic i.v. Glucose Infusions in Individuals with and without Type 2 Diabetes

“…Further, factors previously reported to influence circulating levels of sRAGE and sRAGE ligands such as AGEs [ 20 , 21 ] were stringently matched between groups in the present study, including age, adiposity, and gender. Baseline sRAGE serum concentrations tended to be negatively associated with waist circumference, in agreement with previous studies showing lower circulating sRAGE [ 22 , 23 ] and AGE [ 24 , 25 ] concentrations in obese or overweight individuals populations as compared to lean controls. This decline in circulating sRAGE with obesity is postulated to result from sequestration of AGEs by sRAGE into adipose tissue, as reported in pre-clinical models [ 26 ].…”

Increased glycated albumin and decreased esRAGE levels in serum are related to negative coronary artery remodeling in patients with type 2 diabetes: an Intravascular ultrasound study

“…We did not examine the coronary lesions by IVUS with angiographic diameter stenosis > 70% and < 50%, so the remodeling pattern and relationship of serum levels of GA and esRAGE with remodeling status in mild and severe stenotic lesions were not known. Serum GA and esRAGE levels may vary by race [ 59 , 60 ]. Our findings may also not be applicable to overtly calcified lesions, as these lesions were excluded from this study considering the unreliable measurement of EEM area.…”

Novel dietary factors in diabetic and non-diabetic kidney disease

“…Overall, many factors thought to influence circulating levels of AGEs [456][457][458] were stringently matched between groups including age and adiposity and gender in this study. However, concordant with previous studies in various populations [459][460][461][462][463], we do report a strong positive association between baseline sRAGE and CML concentrations. Baseline sRAGE plasma concentrations were also inversely related to waist to hip ratios.…”

“…Baseline sRAGE plasma concentrations were also inversely related to waist to hip ratios. Lower circulating sRAGE [460,463,464] and AGE [458,460,[463][464][465][466] concentrations have also been reported in obese or overweight populations as compared to lean controls. These studies suggest a down regulation of sRAGE expression with obesity.…”