Adipokines and Cardiovascular Disease in Diabetes

2型糖尿病（DM 2）与冠状动脉疾病（CAD）有因果关系，并且是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DM 2心血管（CV）疾病的发生和进展，但在人群水平上，这些措施仍然不足。目前解决DM2和CV疾病流行的策略可能会通过识别新的病理生理机制而得到极大的增强。脂肪组织是一种生物活性器官，可释放大量的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的心血管预后和各种治疗策略之间的任何关联。治疗效果可能部分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确立。我们提出了一系列新的研究，旨在调查脂肪因子和DM2之间的关联，相关CAD的严重程度，心血管预后，治疗效果和危险分层。本提案旨在作为正在进行的前瞻性旁路血管成形术血运重建研究2D（巴里2D）试验的辅助研究。作为巴里2D方案的一部分，在5年随访期间，将在基线和定期间隔时获得2368例患者的人口统计学、临床特征、传统风险因素、血管造影结果和药物治疗的完整数据。我们将检验以下主要假设：1）胰岛素供应与胰岛素增敏药物治疗对DM 2中脂肪因子水平（或其主要成分）产生不同的纵向效应。2)基线水平和脂肪因子水平（或其主要成分）随时间的变化是DM 2 CV结局的预测因子。3)随机化治疗对DM 2 CV结局的影响由脂肪因子水平（或其主要成分）介导（或促成）。识别参与DM 2患者CAD发展、进展和预后的特定病理生理因素及其对不同治疗方案的反应，将使设计更优化的治疗策略成为可能。

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.