Adipokines and Cardiovascular Disease in Diabetes

2型糖尿病(DM2)与冠状动脉疾病(CAD)有因果关系，是一种主要的健康和经济负担。尽管在过去几十年中实施了多种预防和治疗措施，以减少DM2地区心血管疾病的发生和发展，但在人口层面上，这些措施仍然不够。目前应对DM2和心血管疾病流行的策略可能会通过识别新的病理生理机制而大大加强。脂肪组织是一种生物活性器官，能释放大量旁分泌和内分泌介质(脂肪因子)。脂肪因子水平的变化可能有助于DM2的代谢和心血管后果，也可能有助于解释DM2的心血管预后与各种治疗策略之间的任何关联。治疗效果可能在一定程度上与血浆脂肪因子谱的变化有关。然而，脂肪因子在DM2心血管疾病的病理生理学中的作用尚未得到很好的证实。我们提出了一系列新的研究，旨在调查脂肪因子和DM2之间的相关性，包括相关冠心病的严重程度、心血管预后、治疗效果和风险分层。本提案旨在作为正在进行的前瞻性搭桥血管成形术血管重建术2D(BARI 2D)试验的辅助研究。作为BARI 2D方案的一部分，在为期5年的随访期内，2368名患者将获得关于人口统计学、临床特征、传统风险因素、血管造影结果和医疗治疗的完整数据。我们将检验以下主要假设：1)胰岛素供给治疗和胰岛素增敏药物治疗对DM2中脂肪因子水平(或其主要成分)产生不同的纵向影响。2)基线水平和脂肪因子水平(或其主成分)随时间的变化是预测DM2患者心血管预后的指标。3)在DM2中，随机治疗对心血管预后的影响是由脂肪因子水平(或其主成分)介导(或促成)的。识别与糖尿病患者冠心病的发生、发展和预后有关的特定病理生理因素，以及它们对不同治疗方案的反应，将有助于设计更理想的治疗策略。

Type 2 diabetes mellitus (DM2), is causally associated with coronary artery disease (CAD), and is a major health and economic burden. Despite multiple preventive and therapeutic measures implemented in the last few decades to decrease the occurrence and progression of cardiovascular (CV) disease in DM2, at the population level these measures remain insufficient. Current strategies addressing the epidemic of DM2 and CV disease may be greatly enhanced by the identification of novel pathophysiological mechanisms. Adipose tissue is a bioactive organ that releases numerous paracrine and endocrine mediators (adipokines). Changes in adipokine levels may contribute to metabolic and cardiovascular consequences of DM2, and may also help explain any association between cardiovascular prognosis and various therapeutic strategies in DM2. Effects of treatment may in part be related to changes in plasma adipokine profiles. However, the role of adipokines in the pathophysiology of cardiovascular disease in DM2 has not been well established. We propose a series of novel studies directed at investigating the association between adipokines and DM2, with respect to severity of associated CAD, cardiovascular prognosis, effects of therapy, and risk stratification. The present proposal is intended to be an ancillary study to the ongoing prospective Bypass Angioplasty Revascularization Investigation 2D (BARI 2D) trial. As part of the BARI 2D protocol, complete data regarding demographics, clinical characteristics, traditional risk factors, angiographic findings, and medical treatment will be available in 2368 patients at baseline and at regular intervals, during a 5-year follow-up period. We will test the following primary hypotheses: 1) That treatments with insulin provision versus insulin sensitizing drugs exert differential longitudinal effects on the adipokine levels (or their principal components) in DM2. 2) That baseline levels and changes in adipokine levels (or their principal components) over time are predictors of CV outcome in DM2. 3) That the effect of the randomized treatment on CV outcome in DM2 is mediated (or contributed to) by adipokine levels (or their principal components). Identification of specific pathophysiological factors involved in the development, progression, and prognosis of CAD in individuals with DM2, and their responses to different treatment options, will enable more optimal therapeutic strategies to be designed.