Circulating soluble receptor for advanced glycation end products: relation to vascular complications and oxidative stress in type II diabetic patients

ABSTRACT

Advanced glycation end products [AGEs] and their specific receptor [RAGE] system play an important role in the development of diabetic vascular complications. Recently, an endogenous secretory receptor form, called soluble RAGE [sRAGE] has been identified in human sera. Interestingly, it was reported that sRAGE binds AGE ligands and acts as a decoy receptor that neutralizes AGE actions. To clarify the relationship between serum sRAGE levels and micro-and macrovascular complications as well as oxidative stress in type 2 diabetic patients. This cross-sectional study was conducted on sixty patients with type 2 diabetes mellitus and twenty age and sex matched healthy subjects serving as controls. All patients and control subjects were subjected to a thorough clinical assessment, and measurement of fasting blood glucose, glycosylated haemoglobin [HbA[1C]], lipid profile, 24 hours urinary albumin excretion, high sensitivity CRP [hsCRP],oxidized low density lipoprotein [oxLDL], and sRAGE. The presence of retinopathy and the intima-media thickness [IMT] of the carotid artery were also evaluated. Serum sRAGE levels were significantly lower in patients with type 2 diabetes mellitus compared to control subjects and were inversely correlated with HbA[1C], hsCRP, 24 hours urinary albumin excretion, and oxLDL. Using multiple stepwise regression analysis, HbA[1C],, hsCRP, and urinary albumin excretion remained independent determinants of serum sRAGE levels. In addition, serum sRAGE levels were inversely correlated with mean carotid IMT in diabetic patients only. Also, serum sRAGE levels were significantly lower in diabetic patients with retinopathy compared to those without retinopathy and in diabetic patients with macroalbuminuria compared to those with normo- or microalbuminuria. Serum sRAGE levels were decreased in type 2 diabetic patients and low serum sRAGE levels may be a risk factor for the development and progression of diabetic vascular complications