Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Cardiovasc Diabetol. 2019 Oct 5;18(1):130. doi: 10.1186/s12933-019-0937-7.
Cardiovascular diseases (CVDs) are globally the leading cause of death and hypertension is a significant risk factor. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists has been associated with decreases in blood pressure and CVD risk. Our aim was to investigate the association between endogenous GLP-1 responses to oral glucose and peripheral and central haemodynamic measures in a population at risk of diabetes and CVD.
This cross-sectional study included 837 Danish individuals from the ADDITION-PRO cohort (52% men, median (interquartile range) age 65.5 (59.8 to 70.7) years, BMI 26.1 (23.4 to 28.5) kg/m, without antihypertensive treatment and known diabetes). All participants received an oral glucose tolerance test with measurements of GLP-1 at 0, 30 and 120 min. Aortic stiffness was assessed by pulse wave velocity (PWV). The associations between GLP-1 response and central and brachial blood pressure (BP) and PWV were assessed in linear regression models adjusting for age and sex.
A greater GLP-1 response was associated with lower central systolic and diastolic BP of - 1.17 mmHg (95% confidence interval (CI) - 2.07 to - 0.27 mmHg, P = 0.011) and - 0.74 mmHg (95% CI - 1.29 to - 0.18 mmHg, P = 0.009), respectively, as well as lower brachial systolic and diastolic BP of - 1.27 mmHg (95% CI - 2.20 to - 0.33 mmHg, P = 0.008) and - 1.00 (95% CI - 1.56 to - 0.44 mmHg, P = 0.001), respectively. PWV was not associated with GLP-1 release (P = 0.3). Individuals with the greatest quartile of GLP-1 response had clinically relevant lower BP measures compared to individuals with the lowest quartile of GLP-1 response (central systolic BP: - 4.94 (95% CI - 8.56 to - 1.31) mmHg, central diastolic BP: - 3.05 (95% CI - 5.29 to - 0.80) mmHg, brachial systolic BP: - 5.18 (95% CI - 8.94 to - 1.42) mmHg, and brachial diastolic BP: - 2.96 (95% CI - 5.26 to - 0.67) mmHg).
Greater glucose-stimulated GLP-1 responses were associated with clinically relevant lower central and peripheral blood pressures, consistent with beneficial effects on the cardiovascular system and reduced risk of CVD and mortality. Trial registration ClinicalTrials.gov Identifier: NCT00237549. Retrospectively registered 10 October 2005.
心血管疾病（CVD）是全球范围内导致死亡的主要原因，高血压是一个重要的危险因素。胰高血糖素样肽-1（GLP-1）受体激动剂的治疗与血压降低和 CVD 风险降低有关。我们的目的是研究口服葡萄糖后内源性 GLP-1 反应与糖尿病和 CVD 高危人群的外周和中枢血液动力学测量之间的关系。
这项横断面研究纳入了 ADDITION-PRO 队列中的 837 名丹麦人（52%为男性，中位（四分位间距）年龄 65.5（59.8 至 70.7）岁，BMI 26.1（23.4 至 28.5）kg/m，无抗高血压治疗和已知糖尿病）。所有参与者均接受了口服葡萄糖耐量试验，并在 0、30 和 120 分钟时测量 GLP-1。通过脉搏波速度（PWV）评估主动脉僵硬度。在校正年龄和性别后，使用线性回归模型评估 GLP-1 反应与中心和肱动脉血压（BP）和 PWV 之间的关系。
GLP-1 反应越强，中心收缩压和舒张压分别降低-1.17mmHg（95%置信区间（CI）-2.07 至-0.27mmHg，P=0.011）和-0.74mmHg（95% CI-1.29 至-0.18mmHg，P=0.009），肱动脉收缩压和舒张压也分别降低-1.27mmHg（95% CI-2.20 至-0.33mmHg，P=0.008）和-1.00mmHg（95% CI-1.56 至-0.44mmHg，P=0.001）。GLP-1 释放与 PWV 无关（P=0.3）。与 GLP-1 反应最低四分位的个体相比，GLP-1 反应最高四分位的个体具有临床相关的更低的 BP 测量值（中心收缩压：-4.94mmHg（95% CI-8.56 至-1.31mmHg），中心舒张压：-3.05mmHg（95% CI-5.29 至-0.80mmHg），肱动脉收缩压：-5.18mmHg（95% CI-8.94 至-1.42mmHg），肱动脉舒张压：-2.96mmHg（95% CI-5.26 至-0.67mmHg））。
更强的葡萄糖刺激 GLP-1 反应与临床相关的更低的中心和外周血压相关，这与心血管系统的有益影响和降低 CVD 和死亡率的风险一致。
ClinicalTrials.gov 标识符：NCT00237549。2005 年 10 月 10 日回顾性注册。
