GLP-1类似物exenatide对糖尿病患者心脏舒张功能及内皮依赖性血管舒张的影响

Effects of GLP-1 Agonist Exenatide on Cardiac Diastolic Function and Vascular Endothelial Function in Diabetic Patients

目的研究胰高血糖素样肽-1(GLP-1)受体激动剂艾塞那肽(exenatide)对糖尿病患者心脏舒张功能及血管内皮细胞功能的影响。方法血糖控制欠佳的糖尿病患者随机分为GLP-1组(GLP-1组,n=13)和胰岛素组(INS组,n=12)。在二甲双胍治疗基础上,GLP-1组加用exenatide,胰岛素组加用胰岛素治疗。分别于治疗前、后检测空腹血糖(FBG)、血脂、糖化血红蛋白(HbA1c)、血压及一般临床指标,超声检测左室射血分数(LVEF)、舒张早期二尖瓣最大血流速度(E)、舒张晚期二尖瓣最大血流速度(A),组织多普勒二尖瓣环处舒张早期最大运动速度(e)、组织多普勒二尖瓣环处舒张晚期最大运动速度(a)、肱动脉血流介导的内皮依赖性血管舒张功能(EDV)、硝酸甘油介导的非内皮依赖性血管舒张功能(EIV)。结果经24周治疗后,两组患者FBG、HbA1c水平均较治疗前下降(P<0.05),但治疗后两组间FBG、HbA1c差异无统计学意义(P>0.05)。两组患者治疗前均存在心脏舒张功能减退。治疗后GLP-1组患者二尖瓣环处组织多普勒e峰、e/a值、E/e值改善(P<0.05),而胰岛素组的e峰、e/a值、E/e值较治疗前变化不明显(P>0.05)。两组患者治疗后的EDV较治疗前改善(P<0.01),且治疗后GLP-1组EDV高于胰岛素组(P<0.05)。治疗前后两组间比较EIV无明显变化(P>0.05)。结论 GLP-1可显著改善左室舒张功能及内皮依赖性舒张功能,其心血管功能的改善可能独立于降糖作用之外。

Objective To study the protective effect of glucagon-like peptide-1（GLP-1）on the left ventricular diastolic function and endothelial function in patients with type 2diabetes.Methods 27 patients with type 2diabetes were randomly divided into two groups：GLP-1treated group and insulin treated group.Patients in the GLP-1group were given GLP-1analogue and metformin hydrochloride.Patients in the insulin group were given insulin and metformin hydrochloride.The outcomes of treatments were measured by fasting plasma glucose（FBG）,fasting lipid profile,glycosylated hemoglobin（HbA1c）,blood pressure and general clinical features. High resolution Doppler ultrasound was performed to detect mitral early diastolic rapid filling（E-wave）,atrial contraction late filling（A-wave）,E/A ratio,early diastolic mitral annular velocity（e）,late diastolic mitral annular velocity（a）,e/a ratio,endothelium-dependent vasodilatation（EDV） mediated by brachial arterial blood flow,and endothelium-independent vasodilatation（EIV）mediated by nitroglycerin.Results The levels of FBG and HbA1 c decreased significantly in both groups after treatments（P〈 0.05）.Patients in the GLP-1group showed improved e,e/a ratio,and E/e ratio after treatments（P〈 0.05）,but no significant changed in E,A,and E/A ratio（P〉 0.05）.By contrast,patients in the insulin group showed no significant changes in e,a,E,A,E/A ratio,e/a ratio and E/e ratio after treatments（P〉 0.05）.EDV increased significantly after treatments in both groups（P〈 0.05）.A higher level of post-treatment EDV was found in patients in the GLP-1group compared with those in the insulin group.No significant changes in EIV were found in both groups.Conclusion GLP-1may be able to mitigate the left ventricular diastolic dysfunction and improve endothelial function of patients with type 2diabetes.Our findings suggest that GLP-1 has the potential to prevent or delay cardiovascular complications in patients with type 2diabetes.Further studies are needed.