Myocardial and Vascular Stiffness in Diabetics with Heart Failure and a Norman EF

描述（由申请人提供）： 博士大卫阿吉拉尔是一个非侵入性心脏病专家强烈致力于在临床研究的职业生涯。他在哈佛医学院布里格姆妇女医院完成了内科住院医师和心脏病学奖学金，目前是贝勒医学院的医学助理教授。这个指导职业发展奖（K 01）将通过几种机制发展阿吉拉尔博士的职业生涯，包括每周的指导会议，临床科学家培训计划，以及德克萨斯大学公共卫生学院的教学课程。作为该奖项的一部分，阿吉拉尔博士将解决主动脉和左心室（LV）舒张僵硬度在糖尿病患者的心脏衰竭（HF）和射血分数（EF）正常的重要性，并将测试与胰高血糖素样肽-1（GLP-1）受体激活剂（exengland）的治疗策略对主动脉和LV舒张僵硬度的影响。糖尿病常见于HF和正常EF患者，并与发病率和死亡率增加相关。糖尿病患者中导致这些不良结局的机制尚不清楚，是改善结局的障碍。我们假设，在HF和EF正常的患者中，糖尿病患者的LV舒张刚度将大于非糖尿病患者，并且这种增加的LV舒张刚度将与增加的主动脉刚度相关。我们还假设，这种增加的左心室舒张期僵硬度将与增加的心肌胶原积聚的血清生物标志物相关。晚期糖基化终末产物（AGEs）在这一过程中的重要性也将通过检验主动脉僵硬度和LV舒张期僵硬度增加与血清AGEs水平升高直接相关的假设进行检查。最后，我们假设，在HF和EF正常的个体中，用exenlavin治疗2型糖尿病12周将与主动脉和LV舒张期僵硬度以及异常心肌胶原积聚的血清生物标志物的改善相关。鉴于糖尿病患病率的增加以及糖尿病和EF正常的HF所造成的疾病负担，这项工作具有重要的公共卫生意义。阿吉拉尔博士将研究导致HF和EF正常的糖尿病患者不良结局的机制，并将测试糖尿病特异性治疗策略，希望改善这一高危患者群体的结局。

DESCRIPTION (provided by applicant): Dr. David Aguilar is a non-invasive cardiologist strongly committed to a career in clinical research. He completed his internal medicine residency and cardiology fellowship at the Brigham and Women's Hospital, Harvard Medical School and is currently an Assistant Professor of Medicine at Baylor College of Medicine (BCM). This Mentored Career Development Award (K01) will develop Dr. Aguilar's career through several mechanisms, including weekly mentoring meetings, the Clinical Scientist Training Program, and didactic coursework at the University of Texas School of Public Health and BCM. As part of the award, Dr. Aguilar will address the importance of aortic and left ventricular (LV) diastolic stiffness in diabetic patients with heart failure (HF) and normal ejection fraction (EF) and will test the effects of a treatment strategy with a glucagon-like peptide-1 (GLP-1) receptor activator (exenatide) on aortic and LV diastolic stiffness. Diabetes is commonly seen in patients with HF and normal EF and is associated with increased morbidity and mortality. The mechanisms contributing to these adverse outcomes in diabetic patients are poorly understood and represent a barrier to improving outcomes. We hypothesize that, in patients with HF and normal EF, LV diastolic stiffness will be greater in diabetic patients than in non-diabetic patients and that this increased LV diastolic stiffness will correlate with increased aortic stiffness. We also hypothesize that this increased LV diastolic stiffness will correlate with serum biomarkers of increased myocardial collagen accumulation. The importance of advanced glycation end products (AGEs) in this process will be examined by also testing the hypothesis that increased aortic stiffness and LV diastolic stiffness are directly correlated with increased serum levels of AGEs. Finally, we hypothesize that treatment of type 2 diabetes with exenatide for 12 weeks in individuals with HF and normal EF will be associated with improvement in aortic and LV diastolic stiffness and in serum biomarkers of abnormal myocardial collagen accumulation. Given the increasing prevalence of diabetes and the burden of disease attributed to both diabetes and HF with normal EF, this work has significant public health implications. Dr. Aguilar will study mechanisms contributing to the adverse outcomes in diabetic individuals with HF and normal EF and will test a diabetes-specific treatment strategy in hopes of improving outcomes in this high-risk group of patients.