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

描述（由申请人提供）： David Aguilar 博士是一位无创心脏病专家，致力于临床研究事业。他在哈佛医学院布莱根妇女医院完成了内科住院医师培训和心脏病学专科培训，目前是贝勒医学院 (BCM) 的医学助理教授。该指导职业发展奖 (K01) 将通过多种机制发展阿吉拉尔博士的职业生涯，包括每周指导会议、临床科学家培训计划以及德克萨斯大学公共卫生学院和 BCM 的教学课程。作为该奖项的一部分，Aguilar 博士将探讨主动脉和左心室 (LV) 舒张期僵硬度对于心力衰竭 (HF) 和射血分数 (EF) 正常的糖尿病患者的重要性，并将测试胰高血糖素样肽 1 (GLP-1) 受体激活剂（艾塞那肽）治疗策略对主动脉和左心室舒张期僵硬度的效果。糖尿病常见于 HF 和 EF 正常的患者，并且与发病率和死亡率增加相关。人们对糖尿病患者产生这些不良结果的机制知之甚少，这也是改善结果的障碍。我们假设，在 HF 和 EF 正常的患者中，糖尿病患者的 LV 舒张期硬度将大于非糖尿病患者，并且这种左心室舒张期硬度的增加将与主动脉硬度的增加相关。我们还假设左心室舒张僵硬度的增加与心肌胶原蛋白积累增加的血清生物标志物相关。晚期糖基化终末产物 (AGE) 在此过程中的重要性将通过检验主动脉僵硬度和左心室舒张期僵硬度增加与血清 AGE 水平增加直接相关的假设来检验。最后，我们假设，对心力衰竭和射血分数正常的个体使用艾塞那肽治疗 2 型糖尿病 12 周将与主动脉和左心室舒张期僵硬度以及心肌胶原蛋白异常积累的血清生物标志物的改善相关。鉴于糖尿病患病率不断增加，以及糖尿病和心力衰竭（EF 正常）造成的疾病负担，这项工作具有重大的公共卫生意义。 Aguilar 博士将研究导致 HF 和 EF 正常的糖尿病患者不良结果的机制，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果。

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.