Glycemia and Cardiac Involvement in Friedreich's Ataxia

项目总结/摘要 本研究的首要目标是评估测量的关系， 和弗里德赖希共济失调（FA）患者心脏受累的测量。FA是一种罕见的， 神经肌肉疾病，通常并发糖尿病、葡萄糖耐量受损和 心肌病心肌病是FA患者因心律失常或心脏病而死亡的常见原因 失败本研究将检查血糖变异性增加与 漂移和心脏肥大和功能障碍。为此，我们将利用FA临床 结果测量研究，有1000多名参与者，其中400多人在 费城儿童医院我们将使用连续的 使用稳定同位素口服葡萄糖的葡萄糖监测器以及葡萄糖和胰岛素代谢 耐受性试验从心脏的角度来看，我们将使用两个现成的最近的临床 超声心动图，以及在一个较小的试点队列，详细的超声心动图，以评估 心脏肥大和功能障碍的早期标志物。对该协会的评价将 导致未来的建议，研究干预血糖异常的影响， 改善长期心脏预后。除了这一重要的研究目标， 还提供培训机会。我将通过以下方式学习人类受试者研究的关键技能： 完成这项研究以及统计学和临床试验方面的教学课程。通过利用 稳定同位素口服葡萄糖耐量试验，我将扩展我对乳酸盐的理解， 葡萄糖代谢，以及胰岛素分泌和敏感性的建模。我会完成一个 美国国立卫生研究院关于使用稳定同位素的研讨会，以促进这方面的学习。最后，我将增加我的 了解心脏成像和心血管内分泌学。这种经验和 教学式学习将与持续的专业发展，赠款写作， 手稿写作，并继续获得儿科内分泌学的临床技能， 糖尿病鲁思湖Kirschstein国家研究服务个人奖 博士后研究员（F32）将使我最佳地提出K23职业发展 该奖项促进了这些研究兴趣的临床相关交叉心脏病学和 糖尿病在这种罕见的疾病。

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.