Glycemia and Cardiac Involvement in Friedreich's Ataxia

弗里德赖希共济失调的血糖和心脏受累

基本信息

批准号：
10434538
负责人：
Jaclyn Tamaroff
金额：
$ 7.71万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-11 至 2023-08-08
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10434538
关键词：
Active Learning Adult Adverse effects Appearance Area Under Curve Award Biometry Cardiac Cardiac Myocytes Cardiology Cardiomyopathies Cardiovascular system Cause of Death Child Childhood Clinical Clinical Research Clinical Skills Clinical Trials Collaborations Complement Data Development Diabetes Mellitus Dimensions Echocardiography Educational workshop Endocrinology Environment Evaluation Exercise Fellowship Friedreich Ataxia Functional disorder Future Genes Glucose Glycemic Index Goals Grant Heart Hypertrophy Heart failure Human Human Subject Research Hyperglycemia Hypertrophy Impairment Individual Individual National Research Service Award Inherited Insulin Intervention Intervention Trial K-Series Research Career Programs Knowledge Learning Life Link Manuscripts Measurement Measures Mentorship Metabolic Metabolism Methods Mitochondria Modeling Muscle Proteins Myocardial Myocardial dysfunction Myocardium Natural History Neuromuscular Diseases Non-Insulin-Dependent Diabetes Mellitus OGTT Outcome Participant Pathogenicity Pathway interactions Pediatric Hospitals Phenotype Philadelphia Positioning Attribute Postdoctoral Fellow Production Progressive Disease Protocols documentation Rare Diseases Regression Analysis Research Research Methodology Research Personnel Risk Factors Role Severities Site Skeletal Muscle Techniques Technology Testing Thick Training Training and Infrastructure Trinucleotide Repeats United States National Institutes of Health Variant Writing blood glucose regulation clinical outcome measures clinically relevant cohort diabetes pathogenesis epidemiology study experience frataxin functional status glucose metabolism glucose monitor heart function heart imaging impaired glucose tolerance improved indexing insulin secretion insulin sensitivity interest mathematical model multidisciplinary novel marker patient oriented research prevent skills stable isotope statistics training opportunity

项目摘要

PROJECT SUMMARY/ABSTRACT The overarching goal of this study is to evaluate the relationship between measures of glycemia and measures of cardiac involvement in individuals with Friedreich’s Ataxia (FA). FA is a rare, neuromuscular disorder commonly complicated by diabetes, impaired glucose tolerance, and cardiomyopathy. Cardiomyopathy is a common cause of death in FA due to arrythmias or heart failure. This study will examine the association between increased glucose variability and excursion and cardiac hypertrophy and dysfunction. To do this, we will leverage the FA Clinical Outcomes Measures Study with over 1000 participants, over 400 of whom are followed at the Children’s Hospital of Philadelphia. We will evaluate glycemic variability using continuous glucose monitors and glucose and insulin metabolism using stable-isotope oral glucose tolerance tests. From a cardiac perspective, we will use both readily available recent clinical echocardiograms as well as, in a smaller pilot cohort, detailed echocardiograms to evaluate early markers of cardiac hypertrophy and dysfunction. The evaluation of this association will lead to future proposals studying the impact of intervening on glucose abnormalities in order to improve long term cardiac outcomes. In addition to this important research goal, this proposal also provides training opportunities. I will learn critical skills in human subjects’ research through both the completion of this study and didactic courses in statistics and clinical trials. By utilizing the stable-isotope oral glucose tolerance test, I will extend my understanding of lactate and glucose metabolism, as well as modelling of insulin secretion and sensitivity. I will complete a NIH workshop on the use of stable-isotopes to further this learning. Finally, I will increase my knowledge regarding cardiac imaging and cardiovascular endocrinology. This experiential and didactic learning will be in conjunction with continued professional development, grant writing, manuscript writing, and the continued attainment of clinical skills in pediatric endocrinology and diabetes. The Ruth L. Kirschstein National Research Service Award for the Individual Postdoctoral Fellow (F32) will position me optimally to propose a K23 career development award furthering these research interests on the clinically relevant intersection of cardiology and diabetology in this rare disease.

项目概要/摘要本研究的总体目标是评估血糖测量值之间的关系对弗里德赖希共济失调 (FA) 患者进行心脏受累的测量是一种罕见的情况。神经肌肉疾病通常并发糖尿病、糖耐量受损和心肌病是 FA 中因心律失常或心脏死亡的常见原因。这项研究将检查葡萄糖变异性增加与失败之间的关联。为此，我们将利用 FA 临床。超过 1000 名参与者参与的成果衡量研究，其中 400 多名参与者在我们将使用连续的血糖变异性来评估费城儿童医院。使用稳定同位素口服葡萄糖进行血糖监测以及葡萄糖和胰岛素代谢从心脏的角度来看，我们将使用两种现成的最新临床试验。超声心动图，以及在较小的试点队列中，详细的超声心动图来评估心脏肥大和功能障碍的早期标志物将评估这种关联。导致未来研究干预对葡萄糖异常的影响的建议，以便除了这一重要的研究目标之外，该提案还改善了长期心脏结果。还提供培训机会，我将通过这些学习人类受试者研究的关键技能。通过利用统计和临床试验完成本研究和教学课程。稳定同位素口服葡萄糖耐量试验，我将扩展我对乳酸和我将完成葡萄糖代谢以及胰岛素分泌和敏感性的建模。 NIH 关于使用稳定同位素来进一步学习的研讨会最后，我将增加我的知识。有关心脏成像和心血管内分泌学的知识。教学学习将与持续的专业发展、资助写作、手稿写作，以及继续获得儿科内分泌学和临床技能露丝·L·基尔施斯坦国家研究服务个人奖。博士后研究员 (F32) 将为我提供最佳的 K23 职业发展建议该奖项进一步促进了心脏病学和临床相关交叉领域的研究兴趣糖尿病这种罕见疾病。