Association Between Endogenous Secretory Receptor for Advanced Glycation-end Products (esRAGE) and Carotid Intima-media Thickness in Type 2 Diabetes

Abstract

Background:

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.

Objectives:

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)).

Methods:

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.

Results:

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.

Conclusions:

This study demonstrated that circulating esRAGE levels are independently associated with smaller cIMT in T2DM patients.

Key words

endogenous secretory receptor for advanced ­glycation end-products - Tumor necrosis factor alpha - Interleukin 6 - Atherosclerosis - Diabetes mellitus

^† Equal contributors

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