Higher plasma soluble Receptor for Advanced Glycation End Products (sRAGE) levels are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-year follow-up study. incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-yr follow-up study

AbstractObjective To investigate the associations of plasma levels of soluble receptor for advanced glycation endproducts (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes, and the extent to which any such associations could be explained by endothelial and renal dysfunction, low-grade inflammation, arterial stiffness and advanced glycation endproducts (AGEs). Research design and methods We prospectively followed 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of sRAGE and other biomarkers were measured at baseline. The median follow-up duration was 12.3 (7.6-12.5) years. Results The incidence of fatal and non-fatal CVD and of all-cause mortality increased with higher baseline levels of Ln-sRAGE independently of other CVD risk factors: hazard ratio (HR)=1.90 (95%CI=1.13 to 3.21) and HR=2.12 (1.26 to 3.57) per 1 unit increase in Ln-sRAGE, respectively. Adjustments for estimated glomerular filtration rate (eGFR(MDRD)), but not or to a smaller extent for markers of endothelial dysfunction, low-grade inflammation, arterial stiffness and AGEs, attenuated these associations to HR=1.59 (0.91 to 2.77) for fatal and non-fatal CVD events, and to HR=1.90 (1.09 to 3.31) for all-cause mortality. In addition, in patients with nephropathy the rate of decline of GFR was 1.38 ml/min/1.73 m(2) per year greater per 1 unit increase of Ln-sRAGE at baseline (p=0.036). Conclusions Higher levels of sRAGE are associated with incident fatal and non-fatal CVD, and all-cause mortality in individuals with type 1 diabetes. sRAGE-associated renal dysfunction may partially explain this association.