Establishing the Pathways Between Diabetes and Cardiac Dysfunction: Epidemiology, Biomarkers, and Imaging

项目摘要/摘要 Justin Echouffo Tcheugui，医学博士，约翰斯医院内分泌科助理教授 霍普金斯大学医学院。他寻求K23指导下的以患者为导向的研究生涯 发展奖，以获得基本技能和指导的研究经验，作为独立的职业生涯 新陈代谢和心血管疾病领域的内科科学家。他的研究提案详细说明了 五年计划，总体目标是实现临床、生物标记物和成像特征 糖尿病相关的心功能障碍，包括主要致病途径的确定 以社区为基础的黑人和白人成年人队列，以及以诊所为基础的糖尿病患者样本。 这项研究的具体目的是：1)评估高血糖与纵向变化之间的关系 心脏结构和功能，以及心力衰竭及其亚型的发生率和进展；2)确定新的 糖尿病相关心功能障碍发生的分子途径 蛋白质组学方法；3)评估冠状动脉微血管疾病是否是糖尿病的特异性标志- 使用包括心脏正电子发射在内的双重研究方法，研究相关的心功能不全 微血管功能障碍的体层摄影(PET)和循环生物标志物。这项研究将告知心力衰竭 糖尿病患者的预防和治疗，因为它可能识别与以下方面相关的新生物标记物 与糖尿病相关的心脏功能障碍，可以增强我们对病理生理学的理解，并起到 未来研究中干预措施的潜在目标。在进行拟议研究的同时，申请人将拥有 在先进的流行病学和生物统计学方法方面进行量身定做的深入教学和实践培训， 生物标志物和蛋白质组学研究，以及在心脏PET中作为一种研究性成像技术，以及 通过在新的队列中领导数据收集，发展临床研究设计和性能方面的专业知识。 所获得的技能将填补申请者的关键培训空白，从而使Echouffo Tcheugui博士能够成为 成功的独立资助的研究事业。他的长期目标是建立一个研究项目 旨在促进对糖尿病心血管并发症的了解，并预示未来 糖尿病患者心血管风险预测和预防策略。

PROJECT SUMMARY/ABSTRACT Justin Echouffo Tcheugui, MD, PhD is an Assistant Professor in the Division of Endocrinology at the Johns Hopkins University School of Medicine. He seeks a K23 Mentored Patient-Oriented Research Career Development Award to obtain essential skills and mentored research experience for an independent career as a physician scientist in the field of metabolism and cardiovascular diseases. His research proposal details a five-year plan, with an overarching goal of achieving a clinical, biomarker and imaging characterization of diabetes-related cardiac dysfunction including an identification of key pathways of pathogenicity, in a large community-based cohort of black and white adults, and in a clinic-based sample of individuals with diabetes. The specific aims of the research are: 1) Assess the association of hyperglycemia with longitudinal changes in cardiac structure and function, and incidence and progression of heart failure and its subtypes; 2) Identify novel molecular pathways underlying the occurrence of diabetes-related cardiac dysfunction, using a plasma proteomic approach; 3) Evaluate whether coronary microvascular disease is a specific marker of diabetes- related cardiac dysfunction, using a dual investigative approach including cardiac positron emission tomography (PET) and circulation biomarkers of microvascular dysfunction. This study will inform heart failure prevention and treatment among individuals with diabetes, as it may identify novel biomarkers associated with diabetes-related cardiac dysfunction that can enhance our understanding of pathophysiology and serve as potential targets for interventions in future studies. Concurrent to the proposed research, the applicant will have tailored, in-depth didactic and hands-on training in advanced epidemiologic and biostatistics methods, biomarker and proteomics research, and in cardiac PET as an investigative imaging technique, as well as develop expertise in the design and performance of clinical studies, by leading data collection in a new cohort. The acquired skills will fill key training gaps for the applicant, thereby positioning Dr. Echouffo Tcheugui for a successful independently funded research career. His long-term goals are to establish a research program aimed at advancing the understanding of cardiovascular complications in diabetes, and informing future strategies for cardiovascular risk prediction and prevention among individuals with diabetes.