The correlation between toll like receptor 4 and carotid intima-media thickness in patients with type 2 diabetes

Abstract

Objective To investigate the correlation between toll like receptor 4(TLR4)pathway and carotid intima-media thickness(CIMT)in patients with type 2 diabetes mellitus(T2DM). Methods A total of 66 patients with T2DM were classified into two groups based on the value of CIMT, T2DM without macrovascular injury group(CIMT <0.9 mm, 20 subjects)and T2DM with macrovascular injury group(CIMT≥0.9 mm, or with plaques, 46 subjects), 40 gender and age matched healthy subjects were used as the control group. The CIMT, serum levels of high-sensitivity C-reactive protein(hs-CRP), interleukin-6(IL-6), and monocyte chemotactic protein-1(MCP-1)were tested. The level of TLR4 protein expression on peripheral blood monocyte cells was detected using flow cytometry. Single-factor analysis of variance, Pearson linear analysis, multivariate linear stepwise regression model, and Logistic regression model were performed to analyze the data. Results The level of TLR4 in T2DM with macrovascular injury group was significantly higher than that in both the T2DM without macrovascular injury group and the control group[(18.60±4.64 vs 14.92±3.47, 12.80±2.60), all P<0.05]. In addition, the levels of IL-6, hs-CRP, and MCP-1 in T2DM with macrovascular injury group were significantly increased as compared with those in control group[(6.08±3.16 vs 4.52±2.04)pg/ml, (2.67±2.40 vs 1.53±1.49)mg/dl, (307.99±113.39 vs 242.50±48.04)pg/ml, respectively all P<0.05], but there was no significant difference between T2DM with macrovascular injury group and T2DM without macrovascular injury group. Pearson linear analysis showed that CIMT was positively correlated with TLR4, IL-6, hs-CRP, MCP-1 levels, age, fasting blood glucose, HbA1C, and homeostasis model assessment for insulin resistance(HOMA-IR)(r=0.540, 0.244, 0.271, 0.329, 0.381, 0.490, 0.471, 0.410, respectively, all P<0.05), while negatively correlated with the level of high density lipoprotein-cholesterol(HDL-C)(r=-0.323, P<0.05). TLR4 level was also positively correlated with the level of CIMT, HOMA-IR, IL-6, hs-CRP, and MCP-1(r=0.540, 0.428, 0.214, 0.242, 0.385, respectively, all P<0.05), while negatively correlated with the level of HDL-C(r=-0.384, P<0.05). Multivariate linear stepwise regression analysis showed that TLR4, age, and fasting blood glucose are the independent risk factors for CIMT in patients with type 2 diabetes(R2=0.292, 0.423, 0.492, all P<0.05). Logistic regression analysis showed that the increased TLR4 level was a risk factor of carotid artery plaque formation(OR=1.345, 95%CI 1.10-1.64, P<0.05). Conclusions The increased TLR4 level is a risk factor for the plaque formation in carotid, and that the TLR4 inflammatory signaling pathway seems to be involved in the pathogenesis of macrovascular injury in T2DM.(Chin J Endocrinol Metab, 2015, 31: 1017-1021) Key words: Diabetes mellitus, type 2; Toll-like receptor 4; Atherosclerosis; Carotid intima-media thickness