在 Bypass Angioplasty Revascularization Investigation 2 Diabetes（BARI 2D）试验中，胰岛素增敏策略对纤维蛋白溶解、抗血栓和抗炎的影响。
Profibrinolytic, antithrombotic, and antiinflammatory effects of an insulin-sensitizing strategy in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.
机构信息
Cardiovascular Research Institute, University of Vermont, Colchester Research Facility, Colchester, VT 05446, USA.
出版信息
Circulation. 2011 Aug 9;124(6):695-703. doi: 10.1161/CIRCULATIONAHA.110.014860. Epub 2011 Jul 18.
BACKGROUND
Effects were compared in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial of 2 mechanistically different strategies for treatment of hyperglycemia, insulin-sensitizing and insulin-providing strategies, on biomarker profiles reflecting the balance between fibrinolysis and thrombosis and the intensity of inflammation implicated in diabetic vasculopathy.
METHODS AND RESULTS
A total of 2368 patients with type 2 diabetes mellitus and clinically stable, angiographically documented coronary artery disease were randomized to treatment with 1 of the 2 strategies and followed for an average of 5 years. Plasminogen activator inhibitor type 1 antigen and activity, tissue plasminogen activator antigen, fibrinogen, D-dimer, C-reactive protein, insulin, and hemoglobin A(1c) were assayed in blood samples acquired at baseline and at 12 regular intervals throughout the follow-up interval. Higher baseline D-dimer, fibrinogen, and C-reactive protein portended a poor prognosis in patients in both groups. In contrast to the insulin-providing strategy, the insulin-sensitizing strategy led to (1) lower plasma insulin; (2) lower plasminogen activator inhibitor type 1 antigen and activity and lower tissue plasminogen activator antigen (known to track with plasminogen activator inhibitor type 1); and (3) lower C-reactive protein and fibrinogen at all intervals after baseline (P<0.001 for each).
CONCLUSIONS
The insulin-sensitizing treatment strategy led to changes in biomarker profiles indicative of decreased insulin resistance, an altered balance between thrombosis and fibrinolysis favoring fibrinolysis, and diminished intensity of the systemic inflammatory state, factors that have been associated with cardiovascular risk.
CLINICAL TRIAL REGISTRATION
http://www.clinicaltrials.gov. Unique identifier: NCT00006305.
背景
在 BARI 2D 试验中，比较了两种机制不同的高血糖治疗策略（胰岛素增敏和胰岛素提供策略）对反映纤溶与血栓平衡以及糖尿病血管病变中炎症强度的生物标志物谱的影响。
方法和结果
共有 2368 例 2 型糖尿病和临床稳定、血管造影证实的冠心病患者被随机分配接受 2 种策略中的 1 种治疗，并平均随访 5 年。在基线和随访期间的 12 个常规间隔采集血样，检测纤溶酶原激活物抑制剂 1 抗原和活性、组织型纤溶酶原激活物抗原、纤维蛋白原、D-二聚体、C 反应蛋白、胰岛素和血红蛋白 A1c。两组患者的基线 D-二聚体、纤维蛋白原和 C 反应蛋白较高预示预后不良。与胰岛素提供策略相比，胰岛素增敏策略导致（1）血浆胰岛素降低；（2）纤溶酶原激活物抑制剂 1 抗原和活性以及组织型纤溶酶原激活物抗原降低（与纤溶酶原激活物抑制剂 1 相关）；（3）基线后所有时间点的 C 反应蛋白和纤维蛋白原降低（P<0.001）。
结论
胰岛素增敏治疗策略导致生物标志物谱的变化，表明胰岛素抵抗降低，血栓与纤溶平衡向纤溶倾斜，全身炎症状态强度降低，这些因素与心血管风险相关。
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