Paclíková Markéta, Konečný Lukáš, Carazo Alejandro, Matoušová Kateřina, Krčmová Lenka Kujovská, Blaha Vladimír, Šmahelová Alena, Mladěnka Přemysl
Department of Internal Medicine-Metabolic Care and Gerontology, Faculty of Medicine in Hradec Králové, University Hospital, Charles University, Hradec Králové, Czech Republic.
Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic.
Cardiovasc Diabetol. 2025 Aug 7;24(1):323. doi: 10.1186/s12933-025-02891-6.
It is well known that platelets from diabetic patients can be resistant to clinically used antiplatelet drugs.
To assess the phenomenon in more detail, 50 adult patients suffering from type 1 diabetes mellitus (T1D) were recruited and their responses to 7 platelet aggregation inducers, as well as to 3 clinically used antiplatelet drugs (acetylsalicylic acid /ASA/, ticagrelor and vorapaxar) and one experimental compound, 4-methylcatechol, were assessed ex vivo. A control group of 50 generally healthy age-matched controls was also included for comparison.
T1D patients exhibited a lower aggregation reaction to 3 inducers but were conversely more resistant to the effect of ASA and vorapaxar than controls. Ticagrelor tended to be less active in T1D as well. On the other hand, 4-methylcatechol was equally or even more potent in T1D than in healthy controls. Plasma glucose levels above 7 mM were associated with lower platelet aggregation responses to four aggregation inducers. In contrast, the effect of 4-methylcatechol, unlike that of ASA, did not appear to be strongly influenced by glycemia. Further subanalyses, excluding hypertensive patients and significantly more frequently administered drugs, did not substantially modify the results.
Conclusively, 4-methylcatechol seems to be a prototypical antiplatelet compound with a strong effect even in diabetic patients.
众所周知,糖尿病患者的血小板可能对临床使用的抗血小板药物产生耐药性。
为了更详细地评估这一现象,招募了50名成年1型糖尿病(T1D)患者,对他们离体状态下对7种血小板聚集诱导剂、3种临床使用的抗血小板药物(乙酰水杨酸/ASA/、替格瑞洛和沃拉帕沙)以及一种实验性化合物4-甲基邻苯二酚的反应进行了评估。还纳入了50名年龄匹配的一般健康对照者作为对照组进行比较。
T1D患者对3种诱导剂的聚集反应较低,但与对照组相比,对ASA和沃拉帕沙的作用具有更高的耐药性。替格瑞洛在T1D患者中的活性也往往较低。另一方面,4-甲基邻苯二酚在T1D患者中的作用与健康对照者相当,甚至更强。血糖水平高于7 mM与对四种聚集诱导剂的血小板聚集反应较低有关。相比之下,与ASA不同,4-甲基邻苯二酚的作用似乎不受血糖影响。进一步的亚组分析,排除高血压患者和使用频率明显更高的药物后,结果没有实质性改变。
总之,4-甲基邻苯二酚似乎是一种典型的抗血小板化合物,即使在糖尿病患者中也有很强的作用。