Arterial stiffness and advanced glycation end products in type 2 diabetes mellitus

Abstract

Aim: Binding of advanced glycation end products (AGEs) to theircellular receptors plays an important role in the development ofdiabetic vascular complications and animal studies have shown that thesoluble receptor for advanced glycation end products (sRAGE) may havecytoprotective properties by acting as a decoy. An inverse associationbetween endogenous sRAGE level and carotid intima-media thicknesshas recently been reported in type 1 diabetic patients. We haveinvestigated whether there is an association between arterial stiffnessand serum levels of AGEs and sRAGE in patients with type 2 diabetesmellitus.Methods: Arterial stiffness was assessed non-invasively by measuringcarotid-femoral pulse wave velocity (PWV). Serum sRAGE was assayed byan ELISA kit (R&D Systems) and serum AGEs by competitive ELISA using apolyclonal rabbit antisera raised against AGE-RNase.Results: PWV was significantly increased in type 2 diabetic patients(n = 137) compared with healthy age-matched controls (n = 67)(9.3 ± 2.2 m/s vs. 7.3 ± 1.2 respectively, P<0.01). In the diabeticpatients, PWV correlated with age (r = 0.50, P<0.01), body mass index(r = 0.21, P = 0.01), HDL (r = -0.18, P = 0.03), systolic BP (r = 0.54,P<0.01), serum AGEs (r = 0.33, P<0.01) but not with sRAGE. Todetermine what were the determinants of PWV, stepwise linearregression analysis was performed. Gender, smoking status, duration ofdiabetes and continuous variables which showed an association withPWV on univariate analysis were entered into the model. Systolic BP, age,serum AGEs, body mass index and duration of diabetes were found to beindependent determinants of PWV.Conclusion: Arterial stiffness is increased in type 2 diabetic patients andis associated with serum AGEs but not sRAGE. The association betweenserum AGEs and arterial stiffness is independent of the classicalcardiovascular risk factors.