Suguro Toshiaki, Watanabe Takuya, Kodate Syuusuke, Xu Gang, Hirano Tsutomu, Adachi Mitsuru, Miyazaki Akira
First Department of Internal Medicine, Showa University School of Medicine, Tokyo 142-8666, Japan.
Clin Sci (Lond). 2008 Dec;115(11):327-34. doi: 10.1042/CS20080014.
Human U-II (urotensin-II), the most potent vasoconstrictor peptide identified to date, is associated with cardiovascular disease. A single nucleotide polymorphism (S89N) in the gene encoding U-II (UTS2) is associated with the onset of Type 2 diabetes and insulin resistance in the Japanese population. In the present study, we have demonstrated a relationship between plasma U-II levels and the progression of diabetic retinopathy and vascular complications in patients with Type 2 diabetes. Eye fundus, IMT (intima-media thickness) and plaque score in the carotid artery, BP (blood pressure), FPG (fasting plasma glucose), HbA(1c) (glycated haemoglobin), U-II, angiogenesis-stimulating factors, such as VEGF (vascular endothelial growth factor) and heregulin-beta(1), and lipid profiles were determined in 64 patients with Type 2 diabetes and 24 non-diabetic controls. FPG, HbA(1c) and VEGF levels were significantly higher in patients with Type 2 diabetes than in non-diabetic controls. Diabetes duration, insufficient glycaemic and BP control, plasma U-II levels, IMT, plaque score and nephropathy grade increased significantly across the subjects as follows: non-diabetic controls, patients with Type 2 diabetes without retinopathy (group N), patients with Type 2 diabetes with simple (background) retinopathy (group A) and patients with Type 2 diabetes with pre-proliferative and proliferative retinopathy (group B). The prevalence of obesity and smoking, age, low-density lipoprotein, triacylglycerols (triglycerides) and heregulin-beta(1) were not significantly different among the four groups. In all subjects, U-II levels were significantly positively correlated with IMT, FPG, and systolic and diastolic BP. Multiple logistic regression analysis revealed that, of the above parameters, U-II levels alone had a significantly independent association with diabetic retinopathy. In conclusion, the results of the present study provide the first evidence that increased plasma U-II levels may be associated with the progression of diabetic retinopathy and carotid atherosclerosis in patients with Type 2 diabetes.
人尿调素-II（U-II）是迄今为止发现的最强效的血管收缩肽，与心血管疾病相关。编码U-II的基因（UTS2）中的单核苷酸多态性（S89N）与日本人群2型糖尿病的发病及胰岛素抵抗有关。在本研究中，我们证实了2型糖尿病患者血浆U-II水平与糖尿病视网膜病变进展及血管并发症之间的关系。对64例2型糖尿病患者和24例非糖尿病对照者测定了眼底、颈动脉内膜中层厚度（IMT）和斑块评分、血压（BP）、空腹血糖（FPG）、糖化血红蛋白（HbA1c）、U-II、血管生成刺激因子如血管内皮生长因子（VEGF）和神经调节蛋白-β1以及血脂谱。2型糖尿病患者的FPG、HbA1c和VEGF水平显著高于非糖尿病对照者。糖尿病病程、血糖和血压控制不佳、血浆U-II水平、IMT、斑块评分和肾病分级在以下受试者中显著增加：非糖尿病对照者、无视网膜病变的2型糖尿病患者（N组）、有单纯（背景）视网膜病变的2型糖尿病患者（A组）和有增殖前期及增殖性视网膜病变的2型糖尿病患者（B组）。肥胖和吸烟的患病率、年龄、低密度脂蛋白、三酰甘油（甘油三酯）和神经调节蛋白-β1在四组之间无显著差异。在所有受试者中，U-II水平与IMT、FPG以及收缩压和舒张压显著正相关。多因素逻辑回归分析显示，在上述参数中，仅U-II水平与糖尿病视网膜病变有显著独立关联。总之，本研究结果首次证明，血浆U-II水平升高可能与2型糖尿病患者糖尿病视网膜病变的进展及颈动脉粥样硬化有关。
