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利拉鲁肽对 2 型糖尿病患者肾功能和血管活性激素的短期影响:一项随机临床试验。

Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial.

机构信息

Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.

Novo Nordisk A/S, Bagsvaerd, Denmark.

出版信息

Diabetes Obes Metab. 2016 Jun;18(6):581-9. doi: 10.1111/dom.12651. Epub 2016 Mar 22.

Abstract

AIMS

To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal variables in patients with type 2 diabetes.

METHODS

The study was a placebo-controlled, double-blind, crossover trial in 11 male patients with type 2 diabetes. Measurements included (51) Cr-EDTA plasma clearance estimated glomerular filtration rate (GFR) and MRI-based renal blood flow (RBF), tissue perfusion and oxygenation.

RESULTS

Liraglutide had no effect on GFR [95% confidence interval (CI) -6.8 to 3.6 ml/min/1.73 m(2) ] or on RBF (95% CI -39 to 30 ml/min) and did not change local renal blood perfusion or oxygenation. The fractional excretion of lithium increased by 14% (p = 0.01) and sodium clearance tended to increase (p = 0.06). Liraglutide increased diastolic and systolic blood pressure (3 and 6 mm Hg) and heart rate (2 beats per min; all p < 0.05). Angiotensin II (ANG II) concentration decreased by 21% (p = 0.02), but there were no effects on other renin-angiotensin system components, atrial natriuretic peptides (ANPs), methanephrines or excretion of catecholamines.

CONCLUSIONS

Short-term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short-term as opposed to long-term treatment. Catecholamine levels were unchanged and the results did not support a GLP-1-ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP-1 receptor agonists.

摘要

目的

研究每日 1 次给予 1.2mg 利拉鲁肽(一种胰高血糖素样肽-1(GLP-1)受体激动剂)对 2 型糖尿病患者的主要肾脏变量的影响。

方法

这是一项安慰剂对照、双盲、交叉临床试验,共纳入 11 名 2 型糖尿病男性患者。测量包括(51)Cr-EDTA 血浆清除率估计肾小球滤过率(GFR)和 MRI 测量的肾血流(RBF)、组织灌注和氧合。

结果

利拉鲁肽对 GFR 无影响[95%可信区间(CI)-6.8 至 3.6ml/min/1.73m2]或 RBF(95%CI-39 至 30ml/min),也未改变局部肾血流灌注或氧合。锂的排泄分数增加 14%(p=0.01),钠清除率有增加的趋势(p=0.06)。利拉鲁肽使舒张压和收缩压分别升高 3mmHg 和 6mmHg(均 p<0.05)和心率增加 2 次/分钟(p<0.05)。血管紧张素 II(ANG II)浓度降低 21%(p=0.02),但对其他肾素-血管紧张素系统成分、心房利钠肽(ANP)、甲氧基肾上腺素或儿茶酚胺的排泄无影响。

结论

短期利拉鲁肽治疗不影响肾血流动力学,但可降低近端肾小管钠重吸收。与长期治疗相比,短期治疗会使血压升高。儿茶酚胺水平不变,结果不支持 GLP-1-ANP 轴。ANG II 水平降低,这可能是 GLP-1 受体激动剂发挥肾脏保护作用的原因。

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