Glycemia and Cardiac Involvement in Friedreich's Ataxia

项目摘要/摘要 这项研究的首要目标是评估血糖指标之间的关系。 以及弗里德里希共济失调(FA)患者心脏受累的测量。FA是一种罕见的， 神经肌肉疾病通常合并糖尿病、糖耐量受损和 心肌病。在FA中，心肌病是由于心律失常或心脏引起的常见死亡原因 失败了。这项研究将检验血糖变异性增加和 远足和心脏肥大和功能障碍。要做到这一点，我们将利用FA临床 有1000多名参与者参与了这项研究，其中400多人在 费城儿童医院。我们将使用连续的方法评估血糖变异性 使用稳定同位素口服葡萄糖监测血糖和葡萄糖和胰岛素代谢 耐受性测试。从心脏的角度来看，我们将使用现成的近期临床 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 心肌肥大和功能障碍的早期标志物。对该协会的评估将 导致未来研究干预对血糖异常的影响的建议，以便 改善长期心脏结局。除了这个重要的研究目标之外，这个提议 还提供培训机会。我将通过以下途径学习人类受试者研究的关键技能 完成这项研究和教学课程的统计学和临床试验。通过利用 稳定同位素口服葡萄糖耐量试验，我会扩大我对乳酸和 葡萄糖代谢，以及胰岛素分泌和敏感性的模型。我将完成一份 美国国立卫生研究院关于使用稳定同位素以促进这一学习的讲习班。最后，我会增加我的 心脏影像和心血管内分泌学方面的知识。这是体验式的和 授课学习将与持续的专业发展、拨款写作、 手稿写作，以及继续获得儿科内分泌学和临床技能 糖尿病。Ruth L.Kirschstein个人国家研究服务奖 博士后研究员(F32)将使我成为K23职业发展的最佳人选 授予在心脏病学和临床相关交叉学科上进一步研究这些兴趣的奖项 糖尿病在这种罕见疾病中的作用。

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.