Gohda Tomohito, Tanimoto Mitsuo, Moon Ju-Young, Gotoh Hiromichi, Aoki Tatsuya, Matsumoto Masakazu, Shibata Terumi, Ohsawa Isao, Funabiki Kazuhiko, Tomino Yasuhiko
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
Diabetes Res Clin Pract. 2008 Aug;81(2):196-201. doi: 10.1016/j.diabres.2008.04.013. Epub 2008 Jun 11.
The binding of advanced glycation end-products (AGEs) to their receptor for AGEs (RAGE) may play an important role in the development of diabetic vascular complications. Recently, soluble RAGE (sRAGE) has been identified as an alternative splicing form of RAGE. Furthermore, administration of sRAGE improved atherosclerosis in type 2 diabetic mice.
The objective of the present study is to investigate the role of endogenous secretory RAGE (esRAGE) as a biological marker for type 2 diabetic nephropathy, and also to determine whether serum esRAGE levels are associated with serum AGEs [including Nepsilon-(carboxymethyl) lysine-protein adducts (CML) and pentosidine] levels.
Serum esRAGE levels were examined in 107 type 2 diabetic patients including those on hemodialysis (HD). Diabetic patients were divided into three groups as follows: Group A [patients without nephropathy, i.e. normoalbuminuric stage (AER<30microg/mg creatinine)], Group B [patients with nephropathy (AER>30microg/mg creatinine) but excluding HD patients], and Group C (HD patients).
Serum esRAGE and AGEs (including CML and pentosidine) levels in Group C were significantly higher than in Group A or B. In single linear univariate correlation, serum esRAGE levels were correlated using body mass index (BMI), duration of diabetes, and serum creatinine, high-density lipoprotein (HDL)-cholesterol and AGEs (including CML and pentosidine) levels. Furthermore, in stepwise multivariate regression analysis, the levels of serum creatinine and duration of diabetes were independently associated with serum esRAGE levels.
Serum esRAGE levels are associated with the severity of renal dysfunction and duration of diabetes in type 2 diabetic patients.
晚期糖基化终末产物（AGEs）与其受体（RAGE）的结合可能在糖尿病血管并发症的发生发展中起重要作用。最近，可溶性RAGE（sRAGE）已被鉴定为RAGE的一种可变剪接形式。此外，给予sRAGE可改善2型糖尿病小鼠的动脉粥样硬化。
本研究旨在探讨内源性分泌型RAGE（esRAGE）作为2型糖尿病肾病生物标志物的作用，并确定血清esRAGE水平是否与血清AGEs[包括Nε-（羧甲基）赖氨酸-蛋白质加合物（CML）和戊糖苷]水平相关。
检测了107例2型糖尿病患者（包括接受血液透析的患者）的血清esRAGE水平。糖尿病患者分为以下三组：A组[无肾病患者，即正常白蛋白尿期（尿白蛋白排泄率<30μg/mg肌酐）]，B组[有肾病患者（尿白蛋白排泄率>30μg/mg肌酐）但不包括血液透析患者]，C组（血液透析患者）。
C组血清esRAGE和AGEs（包括CML和戊糖苷）水平显著高于A组或B组。在单一线性单变量相关性分析中，血清esRAGE水平与体重指数（BMI）、糖尿病病程、血清肌酐、高密度脂蛋白（HDL）胆固醇以及AGEs（包括CML和戊糖苷）水平相关。此外，在逐步多变量回归分析中，血清肌酐水平和糖尿病病程与血清esRAGE水平独立相关。
2型糖尿病患者血清esRAGE水平与肾功能不全的严重程度及糖尿病病程相关。
