糖尿病患者血栓形成环境的增强有助于增加血管事件的风险。阿司匹林,一种关键的抗血小板药物,对糖尿病结局的影响不一致,最佳给药方案仍不清楚.这项工作研究了阿司匹林剂量以及与血糖的相互作用对血栓形成的细胞和蛋白质成分的影响。
在一项开放标签交叉研究中,共有48名1型糖尿病患者和48名健康对照者被随机分配接受阿司匹林75或300毫克,每天一次(OD)。在每个治疗期之前和结束时进行透光率聚集测定法和纤维蛋白凝块研究。
与对照组相比,阿司匹林对糖尿病患者胶原诱导的血小板聚集(PA)的抑制作用降低,虽然较高的剂量显示出更好的疗效。较高的阿司匹林剂量促进了对照组的凝块溶解,而不是糖尿病患者。胶原蛋白诱导的PA与血糖控制相关,HbA1c最高的人群对阿司匹林的抑制作用较小。阈值分析表明,>65mmol/mol和>70mmol/mol的HbA1c水平与每天75和300mg剂量的阿司匹林反应不良相关。分别。较高的HbA1c也与较长的纤维蛋白凝块溶解时间相关。
与对照组相比,糖尿病患者对阿司匹林的抗血小板和促纤维蛋白溶解作用的反应不同。特别是,HbA1c升高的患者使用阿司匹林对PA的抑制作用降低.我们的研究结果表明,降低葡萄糖水平可以改善阿司匹林在糖尿病中的抗血栓作用,这可能具有未来的临床意义。
EudraCT,2008-007875-26,https://www.临床试验登记。eu/ctr-search/search?query=2008-007875-26.
The enhanced thrombotic milieu in diabetes contributes to increased risk of vascular events. Aspirin, a key antiplatelet agent, has inconsistent effects on outcomes in diabetes and the best dosing regimen remains unclear. This work investigated effects of aspirin dose and interaction with glycaemia on both the cellular and protein components of thrombosis.
A total of 48 participants with type 1 diabetes and 48 healthy controls were randomised to receive aspirin 75 or 300 mg once-daily (OD) in an open-label crossover
study. Light transmittance aggregometry and fibrin clot studies were performed before and at the end of each treatment period.
Aspirin demonstrated reduced inhibition of collagen-induced platelet aggregation (PA) in participants with diabetes compared with controls, although the higher dose showed better efficacy. Higher aspirin dose facilitated clot lysis in controls but not individuals with diabetes. Collagen-induced PA correlated with glycaemic control, those in the top HbA1c tertile having a lesser inhibitory effect of aspirin. Threshold analysis suggested HbA1c levels of > 65 mmol/mol and > 70 mmol/mol were associated with poor aspirin response to 75 and 300 mg daily doses, respectively. Higher HbA1c was also associated with longer fibrin clot lysis time.
Patients with diabetes respond differently to the antiplatelet and profibrinolytic effects of aspirin compared with controls. In particular, those with elevated HbA1c have reduced inhibition of PA with aspirin. Our findings indicate that reducing glucose levels improves the anti-thrombotic action of aspirin in diabetes, which may have future clinical implications.
EudraCT, 2008-007875-26, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2008-007875-26 .