Endogenous Secretory Receptor for Advanced Glycation End-products in Diabetes with Hyperlipaemia

Background Endogenous secretory receptor (esRAGE) for advanced glycation end-product (AGE), a soluble receptor isoform, acts as decoy for AGEs. We hypothesized that AGE-to-esRAGE ratio could be a 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 concomitant hyperlipaemia. Methods Methylglyoxal-adducts, total AGEs and esRAGE were measured in diabetes without hyperlipaemia (n=32), diabetes with hyperlipaemia (n=98) and hyperlipaemia with normal glucose metabolism (n=38). A history of macrovascular events was recorded in 72 subjects. Results esRAGE level was lower in type 2 diabetic patients compared with the control subjects (0.330±0.197 vs. 0.458±0.074 ng/ml, p=0.003). In diabetes with concomitant hyperlipaemia esRAGE was significantly decreased in comparison with hyperlipaemia (0.306±0.2 vs. 0.367±0.1 ; p=0.019) or diabetes alone (0.306±0.2 vs. 0.404±0.1 ; p=0.004). The calculated AGE-to- esRAGE ratio pointed to increased production of AGEs and low expression of esRAGE. Significantly higher AGE/esRAGE values were found in the subpopulation of diabetic patients with hyperlipaemia (p<0.001). A 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. The results pointed to LDL (β=0.40 p<0.001), HbA1c (β=0.37 p<0.001), 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 High AGE-to-esRAGE ratio and esRAGE down- regulation observed in diabetes with concomitant hyperlipaemia were found to be independent predictors of macrovascular disease.