Karolinska Institutet, Department of Medicine, Cardiology Unit, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden.
Diabetologia. 2012 Mar;55(3):600-7. doi: 10.1007/s00125-011-2415-y. Epub 2011 Dec 27.
AIMS/HYPOTHESIS: Endothelial dysfunction is important in the development of vascular complications in diabetes. Patients with type 2 diabetes have increased production of the vasoconstrictor and pro-inflammatory peptide, endothelin-1. Short-term intra-arterial administration of endothelin antagonists improves endothelium-dependent vasodilatation in patients with type 2 diabetes. We tested the hypothesis that oral administration of the dual endothelin receptor antagonist, bosentan, improves peripheral endothelial function in patients with type 2 diabetes and microalbuminuria.
This placebo-controlled and double-blind study was performed on 46 patients with type 2 diabetes and microalbuminuria (urine albumin/creatinine ratio >3 mg/mmol) at a medical university department. Patients were randomised to bosentan, 125 mg two times per day (n = 28), or placebo (n = 28) for 4 weeks. The computer-generated randomisation code was kept in sealed envelopes. Patients and people doing examinations or assessing outcomes were blinded. The primary endpoint was change in microvascular endothelium-dependent vasodilatation, based on change in digital reactive hyperaemia index. The secondary endpoint was change in brachial artery flow-mediated vasodilatation.
Reactive hyperaemia index increased from 1.73 ± 0.43 (mean ± SD) at baseline to 2.08 ± 0.59 at follow-up (p < 0.05) in the bosentan group (n = 22), but did not change in the placebo group (1.84 ± 0.49 to 1.87 ± 0.47; n = 24). The change in reactive hyperaemia index from baseline was greater in the bosentan group than in the placebo group (p < 0.05). Nitroglycerine-induced digital hyperaemia was not affected. Brachial artery flow-mediated vasodilatation and blood pressure did not change during treatment.
CONCLUSIONS/INTERPRETATION: Oral treatment of 4 weeks duration with the dual endothelin receptor antagonist, bosentan, improves peripheral endothelial function in patients with type 2 diabetes and microalbuminuria.
目的/假设：内皮功能障碍在糖尿病血管并发症的发展中很重要。2 型糖尿病患者内皮素-1的产生增加，内皮素-1 是一种血管收缩和促炎肽。短期动脉内给予内皮素拮抗剂可改善 2 型糖尿病患者的内皮依赖性血管舒张功能。我们检验了这样一个假设，即口服双重内皮素受体拮抗剂波生坦可改善 2 型糖尿病合并微量白蛋白尿患者的外周内皮功能。
该研究在一所医科大学的一个科室进行，共纳入 46 名 2 型糖尿病合并微量白蛋白尿（尿白蛋白/肌酐比值>3mg/mmol）的患者。患者被随机分为波生坦组（n=28）和安慰剂组（n=28），每天两次分别服用 125mg 波生坦或安慰剂，疗程 4 周。计算机生成的随机化代码被保存在密封的信封中。患者和进行检查或评估结果的人员均设盲。主要终点是根据数字反应性充血指数的变化来评估微血管内皮依赖性血管舒张功能的变化。次要终点是肱动脉血流介导的血管舒张功能的变化。
波生坦组（n=22）的反应性充血指数从基线时的 1.73±0.43（均值±标准差）增加到随访时的 2.08±0.59（p<0.05），而安慰剂组（n=24）无变化（1.84±0.49 到 1.87±0.47）。与安慰剂组相比，波生坦组的反应性充血指数从基线的变化更大（p<0.05）。硝酸甘油诱导的手指充血不受影响。肱动脉血流介导的血管舒张功能和血压在治疗期间均无变化。
口服双重内皮素受体拮抗剂波生坦治疗 4 周可改善 2 型糖尿病合并微量白蛋白尿患者的外周内皮功能。
