Nakamura Kazuo, Yamagishi Sho-ichi, Adachi Hisashi, Kurita-Nakamura Yayoi, Matsui Takanori, Yoshida Takafumi, Sato Akira, Imaizumi Tsutomu
Departments of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Diabetes Metab Res Rev. 2007 Jul;23(5):368-71. doi: 10.1002/dmrr.690.
Advanced glycation end products (AGEs)-receptor (RAGE) axis is implicated in diabetic vascular complication. Since a soluble form of RAGE (sRAGE) could be generated from the cleavage of cell surface RAGE in endothelial cells (ECs), serum sRAGE levels may be elevated in diabetes consequent to EC damage. In this study, we examined whether sRAGE levels were elevated in type 2 diabetic patients compared with non-diabetic healthy subjects.
Serum sRAGE levels were examined in 75 Japanese type 2 diabetic patients (29 men and 46 women; mean age 66 +/- 11 years) and 75 age- and sex-matched non-diabetic healthy control subjects. We explored the association between sRAGE levels and coronary artery disease (CAD) in diabetic patients.
Serum sRAGE levels were significantly higher in diabetic patients than in non-diabetic subjects (965.3 +/- 544.2 vs 415 +/- 150.4 pg/mL, p < 0.001). In the univariate analysis, diastolic blood pressure (inversely), LDL cholesterol, triglycerides, HDL cholesterol, hemoglobin A(1c), and creatinine were significantly associated with sRAGE. After performing multivariate analyses, the presence of diabetes (p < 0.0001) was a sole independent determinant of sRAGE. Furthermore, there was a significant difference in sRAGE levels between diabetic patients with CAD and those without CAD (1680.6 +/- 891.1 vs 855.2 +/- 372.1 pg/mL, p < 0.001). Multiple stepwise regression analysis revealed that sRAGE and creatinine levels were independent determinants of CAD.
The present study demonstrated that serum sRAGE levels were significantly higher in type 2 diabetic patients than in non-diabetic subjects and positively associated with the presence of CAD.
晚期糖基化终末产物（AGEs）-受体（RAGE）轴与糖尿病血管并发症有关。由于可溶性RAGE（sRAGE）可由内皮细胞（ECs）表面RAGE的裂解产生，糖尿病患者因EC损伤血清sRAGE水平可能升高。在本研究中，我们检测了2型糖尿病患者与非糖尿病健康受试者相比sRAGE水平是否升高。
检测了75例日本2型糖尿病患者（29例男性和46例女性；平均年龄66±11岁）和75例年龄及性别匹配的非糖尿病健康对照者的血清sRAGE水平。我们探讨了糖尿病患者sRAGE水平与冠状动脉疾病（CAD）之间的关联。
糖尿病患者血清sRAGE水平显著高于非糖尿病受试者（965.3±544.2 vs 415±150.4 pg/mL，p<0.001）。单因素分析中，舒张压（呈负相关）、低密度脂蛋白胆固醇、甘油三酯、高密度脂蛋白胆固醇、糖化血红蛋白A1c和肌酐与sRAGE显著相关。进行多因素分析后，糖尿病的存在（p<0.0001）是sRAGE的唯一独立决定因素。此外，有CAD的糖尿病患者与无CAD的糖尿病患者的sRAGE水平存在显著差异（1680.6±891.1 vs 855.2±372.1 pg/mL，p<0.001）。多元逐步回归分析显示，sRAGE和肌酐水平是CAD的独立决定因素。
本研究表明，2型糖尿病患者血清sRAGE水平显著高于非糖尿病受试者，且与CAD的存在呈正相关。
