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Endogenous secretory receptor for advanced glycation endproducts (esRAGE) and AGEs/esRAGE ratio as biomarkers of atherosclerosis risk in type 2 diabetes

Objective Endogenous secretory receptor for advanced glycation endproducts (esRAGE) an isoform of soluble RAGE, acts as decoy for AGEs. We hypothesized ratio of AGE-to-esRAGE could be link to atherosclerosis in diabetes. To examine this issue, we compared serum levels of esRAGE and methylglyoxal-adduct as well as the AGE-to-esRAGE ratio between type 2 diabetic patients with and without established macrovascular disease. Patients and Methods Methylglyoxal-adducts, AGEs and esRAGE were measured in type 2 diabetes (n=130) and healthy controls (n=30). A history of macrovascular events (cardiovascular disease, cerebral vasculopathy or peripheral vascular disease) was recorded in 50 subjects. Results esRAGE levels were lower in type 2 diabetic patients compared with control subjects (0.330±0.197 vs. 0.458±0.074 ng/ml, p=0.003). In diabetic population es RAGE correlated positively with MG-adducts, HbA1c, BMI, and triglyceride, and inversely with CRP, LDL and homocystein. Multiple stepwise regression analysis was performed to determine which parameters best predicted the esRAGE level. Finally, urinary MG-adduct excretion (p<0.001), AGEs (p<0.001), and AGE/esRAGE (p<0.001, inversely) remained to be independently associated circulatory esRAGE. Multiple stepwise regression model was used to evaluate the relationship between macrovascular disease as a dependent variable, and metabolic and AGE- parameters as independent variables. Analysis pointed to LDL (β=0.40 P=0.0001), HbA1c (β=0.37 P=0.0007), AGE/esRAGE (β=0.31 P=0.007) and homocysteine (β=0.25 P=0.013) as significant independent contributors to diabetic macrovascular disease. Conclusion A decreased level of esRAGE may therefore be a biomarker of atherosclerosis acting as either a decoy receptor or another mechanism.

Advanced glycation pathway; Type 2 diabetes; Hyperlipemia; Macrovascular disease; Endogenous secretory receptor for AGE; AGE-to-esRAGE ratio

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