Association between endogenous secretory receptor for advanced glycation-end products (esRAGE) and carotid intima-media thickness in type 2 diabetes.

Advanced glycation end products (AGEs) contribute to vascular complications in type 2 diabetes (T2DM). Endogenous secretory receptor for advanced glycation end products (esRAGE) may inhibit the pathological effects of AGEs in T2DM vascular complications.To investigate the relationship between esRAGE and diabetic carotid atherosclerosis, using carotid intima-media thickness (cIMT); and to determine if esRAGE influences levels of inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)).Prospective observational study in 308 T2DM subjects (149 men and 159 women). An echotomographic system was used by a blinded operator to measure cIMT. Patients were divided into 2 groups according to cIMT. Body mass index was calculated and serum lipids were measured by an autoanalyzer. Enzyme-linked immunosorbent assays (ELISA) were used to detect serum esRAGE, TNF-α, and IL-6 levels.Patients with a cIMT≥0.9 mm were older (P<0.0001), had more smokers (P=0.01), had a higher systolic blood pressure (SBP) (P<0.0001), and had lower HDL-C levels (P=0.01). esRAGE was lower in patients with a cIMT ≥0.9 mm (0.231±0.135 vs. 0.343±0.164, P<0.0001), while TNF-α levels were elevated (83.68±55.27 vs. 65.71±45.91, P=0.002). There was no difference in IL-6 levels between the 2 groups. Univariate analyses showed that age, T2DM duration, SBP, HDL-C, esRAGE and TNF-α were associated with cIMT. Multivariate analysis showed that age, SBP, HDL-C, smoking and esRAGE levels were independently associated with cIMT, but not TNF-α.This study demonstrated that circulating esRAGE levels are independently associated with smaller cIMT in T2DM patients.