Glycemia and Cardiac Involvement in Friedreich's Ataxia

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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.