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

• 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
• 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

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.

项目总结/文摘