Medical Clinic II, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Diabet Med. 2010 Apr;27(4):384-90. doi: 10.1111/j.1464-5491.2010.02957.x.
Type 2 diabetes is a potent cardiovascular risk factor, associated with proinflammatory and prothrombotic processes. The purpose of this study was to investigate whether platelet-bound CD40-CD40L signalling, P-selectin expression and soluble CD40L were increased in patients with diabetes mellitus and can be normalized by improving glycaemic control.
Soluble (s) CD40L, platelet surface expression of CD40L, CD40 and P-selectin (CD62P) on platelets were measured by flow cytometry in 71 patients with Type 2 diabetes mellitus and 37 healthy volunteers. In addition, the relationship of HbA1c to CD40-CD40L and P-selectin expression was determined in a longitudinal follow-up.
In patients with Type 2 diabetes, platelet membrane CD40 expression (Type 2 diabetes 3.1+/-0.61 vs. controls 2.5+/-0.85 mean fluorescence intensity; P=0.001), platelet-bound CD40L (1.2+/-0.32 vs. 1.1+/-0.14; P=0.034) as well as surface expression of CD62P (0.66+/-0.19 vs. 0.57+/-0.12; P=0.007) were higher than in control subjects. Plasma sCD40L values (3.2+/-1.70 vs. 1.8+/-0.50 ng/ml; P<0.001) were also significantly increased in Type 2 diabetes. After improving glycaemic control in patients with initial HbA1c>8.5% (n=15), platelet P-selectin and CD40-CD40L expression decreased significantly by 54.0%, 36.22% and 16.26%, respectively 1 year later.
Type 2 diabetes is associated with up-regulation of the platelet-bound CD40-CD40L system, platelet hyperactivity (enhanced P-selectin expression) and increased sCD40L levels. Improved glycaemic control, however, does help to correct abnormal platelet activation via down-regulation of CD40-CD40L system and P-selectin expression.
2 型糖尿病是一种强有力的心血管危险因素，与促炎和促血栓形成过程有关。本研究旨在探讨糖尿病患者的血小板结合 CD40-CD40L 信号、P-选择素表达和可溶性 CD40L 是否增加，以及改善血糖控制是否可以使其正常化。
通过流式细胞术测量 71 例 2 型糖尿病患者和 37 名健康志愿者的可溶性 (s) CD40L、血小板表面 CD40L、CD40 和 P-选择素 (CD62P)。此外，在纵向随访中确定 HbA1c 与 CD40-CD40L 和 P-选择素表达的关系。
在 2 型糖尿病患者中，血小板膜 CD40 表达（2 型糖尿病 3.1+/-0.61 对对照 2.5+/-0.85 平均荧光强度；P=0.001）、血小板结合 CD40L（1.2+/-0.32 对 1.1+/-0.14；P=0.034）以及 CD62P 表面表达（0.66+/-0.19 对 0.57+/-0.12；P=0.007）均高于对照组。2 型糖尿病患者的血浆 sCD40L 值（3.2+/-1.70 对 1.8+/-0.50 ng/ml；P<0.001）也显著升高。在初始 HbA1c>8.5%（n=15）的患者中改善血糖控制后，1 年后血小板 P-选择素和 CD40-CD40L 表达分别显著下降 54.0%、36.22%和 16.26%。
2 型糖尿病与血小板结合的 CD40-CD40L 系统上调、血小板活性增强（增强 P-选择素表达）和 sCD40L 水平升高有关。然而，改善血糖控制确实有助于通过下调 CD40-CD40L 系统和 P-选择素表达来纠正异常的血小板激活。
