Schneider David J, Hardison Regina M, Lopes Neuza, Sobel Burton E, Brooks Maria Mori
Cardiology Division and Cardiovascular Research Institute, University of Vermont, Burlington, Vermont, USA.
Diabetes Care. 2009 May;32(5):944-9. doi: 10.2337/dc08-1308. Epub 2009 Feb 19.
To determine whether obesity increases platelet reactivity and thrombin activity in patients with type 2 diabetes plus stable coronary artery disease.
We assessed platelet reactivity and markers of thrombin generation and activity in 193 patients from nine clinical sites of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D). Blood taken at the time of enrollment was used for assay of the concentration of prothrombin fragment 1.2 (PT1.2, released when prothrombin is activated) and fibrinopeptide A (FPA, released when fibrinogen is cleaved). Platelet activation was identified with the use of flow cytometry in response to 0, 0.2, and 1 micromol/l adenosine diphosphate (ADP).
Concentrations of FPA, PT1.2, and platelet activation in the absence of agonist were low. Greater BMI was associated with higher platelet reactivity in response to 1 microm ADP as assessed by surface expression of P-selectin (r = 0.29, P < 0.0001) but not reflected by the binding of fibrinogen to activated glycoprotein IIb-IIIa. BMI was not associated with concentrations of FPA or PT1.2. Platelet reactivity correlated negatively with A1C (P < 0.04), was not related to the concentration of triglycerides in blood, and did not correlate with the concentration of C-reactive peptide. CONCLUSIONS Among patients enrolled in this substudy of BARI 2D, a greater BMI was associated with higher platelet reactivity at the time of enrollment. Our results suggest that obesity and insulin resistance that accompanies obesity may influence platelet reactivity in patients with type 2 diabetes.
确定肥胖是否会增加2型糖尿病合并稳定型冠状动脉疾病患者的血小板反应性和凝血酶活性。
我们评估了来自旁路血管成形术血运重建研究2糖尿病(BARI 2D)九个临床站点的193例患者的血小板反应性以及凝血酶生成和活性标志物。入组时采集的血液用于检测凝血酶原片段1.2(PT1.2,凝血酶原激活时释放)和纤维蛋白肽A(FPA,纤维蛋白原裂解时释放)的浓度。使用流式细胞术鉴定血小板对0、0.2和1微摩尔/升二磷酸腺苷(ADP)的反应性。
在无激动剂的情况下,FPA、PT1.2的浓度以及血小板活化程度较低。通过P-选择素的表面表达评估,较高的体重指数(BMI)与对1微摩尔ADP反应时更高的血小板反应性相关(r = 0.29,P < 0.0001),但纤维蛋白原与活化的糖蛋白IIb-IIIa的结合未反映出这种相关性。BMI与FPA或PT1.2的浓度无关。血小板反应性与糖化血红蛋白(A1C)呈负相关(P < 0.04),与血液中甘油三酯浓度无关,也与C反应肽浓度无关。结论:在参与BARI 2D这项子研究的患者中,较高的BMI与入组时较高的血小板反应性相关。我们的结果表明,肥胖以及伴随肥胖的胰岛素抵抗可能会影响2型糖尿病患者的血小板反应性。