Nakamura Kazuo, Yamagishi Sho-ichi, Adachi Hisashi, Matsui Takanori, Kurita-Nakamura Yayoi, Takeuchi Masayoshi, Inoue Hiroyoshi, Imaizumi Tsutomu
Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Diabetes Metab Res Rev. 2008 Feb;24(2):109-14. doi: 10.1002/dmrr.766.
Atherosclerosis is an inflammatory disease. Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine responsible for the recruitment of monocytes to inflammatory lesions in the vasculature, an initial step of atherosclerosis. Since serum levels of MCP-1 are higher in patients with type 2 diabetes, inhibition of MCP-1 may be a novel therapeutic target for prevention of accelerated atherosclerosis in diabetes. However, little is known about the regulation and determinants of serum MCP-1 levels in patients with diabetes. In this study, we examined the determinants of serum MCP-1 levels in type 2 diabetic patients.
Eighty-six consecutive outpatients with type 2 diabetes (36 male and 50 female; mean age 68.4+/-9.6) underwent a complete history and physical examination, determination of blood chemistries, MCP-1, tumour necrosis factor-alpha, adiponectin, advanced glycation end products (AGEs), and soluble form of receptor for AGEs (sRAGE). We examined the association between MCP-1 levels and those in anthropometric, metabolic and inflammatory variables in these subjects.
Univariate regression analysis showed that serum levels of MCP-1 were positively associated with AGEs (r=0.386, p<0.001) and sRAGE (r=0.315, p<0.001). After adjusting for age and sex, AGEs (p<0.001) and sRAGE (p<0.05) still remained significant.
The results demonstrate for the first time that circulating levels of AGEs and sRAGE are independent determinants of serum MCP-1 levels in patients with type 2 diabetes. Our present observations suggest the AGEs-RAGE system may be mainly involved in the elevation of MCP-1 in type 2 diabetic patients.
动脉粥样硬化是一种炎症性疾病。单核细胞趋化蛋白-1(MCP-1)是一种重要的趋化因子,负责将单核细胞募集到血管中的炎症病变部位,这是动脉粥样硬化的起始步骤。由于2型糖尿病患者的血清MCP-1水平较高,抑制MCP-1可能是预防糖尿病中加速动脉粥样硬化的新治疗靶点。然而,关于糖尿病患者血清MCP-1水平的调节和决定因素知之甚少。在本研究中,我们研究了2型糖尿病患者血清MCP-1水平的决定因素。
86例连续的2型糖尿病门诊患者(36例男性和50例女性;平均年龄68.4±9.6岁)接受了完整的病史和体格检查,测定了血液化学指标、MCP-1、肿瘤坏死因子-α、脂联素、晚期糖基化终产物(AGEs)和AGEs受体的可溶性形式(sRAGE)。我们研究了这些受试者中MCP-1水平与人体测量、代谢和炎症变量之间的关联。
单因素回归分析显示,血清MCP-1水平与AGEs(r=0.386,p<0.001)和sRAGE(r=0.315,p<0.001)呈正相关。在调整年龄和性别后,AGEs(p<0.001)和sRAGE(p<0.05)仍然具有显著性。
结果首次表明,AGEs和sRAGE的循环水平是2型糖尿病患者血清MCP-1水平的独立决定因素。我们目前的观察结果表明,AGEs-RAGE系统可能主要参与2型糖尿病患者MCP-1的升高。