Longitudinal effect of insulin resistance on right ventricular function

项目摘要 胰岛素抵抗是对胰岛素信号的反应减弱，是一个主要的公共卫生问题。在……里面 除了在射血分数保持不变的情况下，胰岛素抵抗是心力衰竭的危险因素，胰岛素抵抗也是一个 在右室重构和功能障碍中的作用。RV函数是一个重要的决定因素 与左心室(LV)功能相比，心血管健康状况的特征要差得多-RV 功能障碍与一般人群和潜在疾病患者的预后较差有关。 心脏病。然而，以前的研究使用了RV功能的负荷依赖测量，这是 使用传统的经胸超声心动图评估是出了名的困难。此外，目前还不清楚 针对胰岛素敏感性的治疗(如二甲双胍和噻唑烷二酮类药物)可以改善RV 功能。选择性地解除胰岛素抵抗对右室的影响，而不是室间 伴随而来的左心功能不全的相互作用带来了额外的挑战。 这项研究的目标是检查胰岛素抵抗对RV谱系的纵向影响 斑点跟踪超声心动图的功能，一种比传统方法更敏感的新方法 右室功能指标。首先，我们将确定胰岛素增敏药物对右心室的影响。 在代表以社区为基础的人群的动脉粥样硬化(MESA)多种族研究中的作用。 第二，我们将研究胰岛素抵抗对慢性阻塞性肺疾病患者右室和左室功能的纵向影响。 肺动脉高压(PAH)，代表有潜在右室功能障碍的队列。 这一建议将提高对右室胰岛素抵抗变化之间的联系的理解 功能。这项研究利用一种新的超声心动图技术来研究一种可能是 未来用于识别RV功能障碍的高危个体，并研究旨在 改善这一人群的胰岛素敏感性。最后，该项目将为 职业发展奖重点研究旨在改善代谢功能的干预措施 有房室功能障碍风险的个体。

Project Summary Insulin resistance is the decreased response to insulin signaling and is a major public health concern. In addition to being a risk factor for heart failure with preserved ejection fraction, insulin resistance also plays a role in right ventricular (RV) remodeling and dysfunction. RV function is an important determinant of cardiovascular health which is much less well-characterized compared to the left ventricular (LV) function – RV dysfunction is associated with worse outcomes in both the general population and in those with underlying cardiac disease. However, prior studies have used load-dependent measures of RV function, which is notoriously difficult to assess using traditional transthoracic echocardiography. Further, it is unknown whether therapies targeting insulin sensitivity (such as metformin and thiazolidinedione medications) could improve RV function. Disentangling the impact of insulin resistance selectively for the RV as opposed to interventricular interaction from concomitant left ventricular dysfunction has posed additional challenges. The goal of this study is to examine the longitudinal impact of insulin resistance across the spectrum of RV function using speckle-tracking echocardiography, a novel method which is more sensitive than traditional indices of RV function. First, we will determine the effect of insulin-sensitizing medications on right ventricular function in the Multi-Ethnic Study of Atherosclerosis (MESA), representing a community-based population. Second, we will examine the longitudinal effect of insulin resistance on RV and LV function in patients with pulmonary arterial hypertension (PAH), representing a cohort with underlying RV dysfunction. This proposal will improve understanding of the association between changes in insulin resistance on RV function. The research utilizes a novel echocardiography technique to study an emerging pathway that may be used in the future to identify individuals at increased risk for RV dysfunction and studying interventions aimed at improving insulin sensitivity on this population. Finally, this project will provide key preliminary data for a Career Development Award focused on studying interventions aimed at improving metabolic function among individuals at risk for RV dysfunction.