Faber Rebekka, Zander Mette, Pena Adam, Michelsen Marie M, Mygind Naja D, Prescott Eva
Department of Cardiology, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark.
Department of Endocrinology, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark.
Cardiovasc Diabetol. 2015 Apr 22;14:41. doi: 10.1186/s12933-015-0206-3.
Impaired coronary microcirculation is associated with a poor prognosis in patients with type 2 diabetes. In the absence of stenosis of major coronary arteries, coronary flow reserve (CFR) reflects coronary microcirculation. Studies have shown beneficial effects of glucagon-like peptide-1 (GLP-1) on the cardiovascular system. The aim of the study was to explore the short-term effect of GLP-1 treatment on coronary microcirculation estimated by CFR in patients with type 2 diabetes.
Patients with type 2 diabetes and no history of coronary artery disease were treated with either the GLP-1 analogue liraglutide or received no treatment for 10 weeks, in a randomized, single-blinded, cross-over setup with a 2 weeks wash-out period. The effect of liraglutide on coronary microcirculation was evaluated using non-invasive trans-thoracic Doppler-flow echocardiography during dipyridamole induced stress. Peripheral microvascular endothelial function was assessed by Endo-PAT2000®. Interventions were compared by two-sample t-test after ensuring no carry over effect.
A total of 24 patients were included. Twenty patients completed the study (15 male; mean age 57 ± 9; mean BMI 33.1 ± 4.4, mean baseline CFR 2.35 ± 0.45). There was a small increase in CFR following liraglutide treatment (change 0.18, CI95% [-0.01; 0.36], p = 0.06) but no difference in effect in comparison with no treatment (difference between treatment allocation 0.16, CI95% [-0.08; 0.40], p = 0.18). Liraglutide significantly reduced glycated haemoglobin (HbA1c) (-10.1 mmol/mol CI95% [-13.9; -6.4], p = 0.01), systolic blood pressure (-10 mmHg CI95% [-17; -3], p = 0.01) and weight (-1.9 kg CI95% [-3.6; -0.2], p = 0.03) compared to no treatment. There was no effect on peripheral microvascular endothelial function after either intervention.
In this short-term treatment study, 10 weeks of liraglutide treatment had no significant effect on neither coronary nor peripheral microvascular function in patients with type 2 diabetes. Further long-term studies, preferably in patients with more impaired microvascular function and using a higher dosage of GLP-1 analogues, are needed to confirm these findings.
ClinicalTrials.gov: NCT01931982 .
冠状动脉微循环受损与2型糖尿病患者的不良预后相关。在主要冠状动脉无狭窄的情况下，冠状动脉血流储备（CFR）反映冠状动脉微循环。研究表明胰高血糖素样肽-1（GLP-1）对心血管系统有有益作用。本研究的目的是探讨GLP-1治疗对2型糖尿病患者通过CFR评估的冠状动脉微循环的短期影响。
将无冠状动脉疾病病史的2型糖尿病患者随机、单盲、交叉分组，接受GLP-1类似物利拉鲁肽治疗或不治疗10周，洗脱期为2周。在双嘧达莫诱导的应激状态下，使用无创经胸多普勒血流超声心动图评估利拉鲁肽对冠状动脉微循环的影响。通过Endo-PAT2000®评估外周微血管内皮功能。在确保无残留效应后，采用两样本t检验比较干预措施。
共纳入24例患者。20例患者完成研究（15例男性；平均年龄57±9岁；平均体重指数33.1±4.4，平均基线CFR 2.35±0.45）。利拉鲁肽治疗后CFR有小幅升高（变化0.18，95%CI[-0.01；0.36]，p=0.06），但与未治疗相比效果无差异（治疗组间差异0.16，95%CI[-0.08；0.40]，p=0.18）。与未治疗相比，利拉鲁肽显著降低糖化血红蛋白（HbA1c）（-10.1 mmol/mol，95%CI[-13.9；-6.4]，p=0.01）、收缩压（-10 mmHg，95%CI[-17；-3]，p=0.01）和体重（-1.9 kg，95%CI[-3.6；-0.2]，p=0.03）。两种干预措施对外周微血管内皮功能均无影响。
在这项短期治疗研究中，10周的利拉鲁肽治疗对2型糖尿病患者的冠状动脉和外周微血管功能均无显著影响。需要进一步的长期研究，最好在微血管功能受损更严重的患者中进行，并使用更高剂量的GLP-1类似物，以证实这些发现。
ClinicalTrials.gov：NCT01931982 。
