Impact of Congenital Hyperinsulinism on Trajectories of Neurocognitive Function Across School Age

项目概要/摘要 此K23应用程序的总体目标是为额外的培训和经验提供支持， 主要研究者，一位儿科内分泌学家和流行病学家，需要建立一个独立的， 以病人为导向的高胰岛素血症研究项目先天性高胰岛素血症（HI）是最常见的 导致婴儿和儿童持续低血糖的原因。HI中低血糖的发作与严重 在生命的最初几年发生的神经认知发展时期。虽然HI儿童更有可能 有神经认知缺陷，关于影响神经认知轨迹的因素知之甚少。 受影响儿童的发展。本研究的目的是：（1）识别HI儿童的神经认知轨迹 采用加速纵向设计，（2）检查时间之间的关系， 通过比较HI的两种临床表型与 临床过程中的自然变化。为了实现这些目标，将建立一个全面的神经认知电池， 在基线时给药，并在基线后1年和2年重复给药， 局灶性HI（低血糖暴露限于生命早期）、弥漫性HI（生命早期和持续低血糖 暴露），年龄、性别和社会经济地位与健康对照组匹配。该项目的成果将填补 关于高胰岛素血症性低血糖在显著脑缺血期间的影响的知识存在重大空白 发展并对临床实践产生重大影响。这项研究也可能具有广泛的影响 用于与高胰岛素血症性低血糖症相关的其他疾病，包括糖尿病。校长 研究人员将充分利用丰富的科学环境和优秀的资源所提供的 费城儿童医院和宾夕法尼亚大学，以实现她的研究和培训目标。 该提案包括纵向数据分析和纵向神经认知结果的高级培训 评估，这将通过教学课程，实践研究的结合来实现 经验和支持形成了一个专家，多学科的指导和咨询团队。支持这篇 K23将使主要研究者能够作为独立研究者开始成功的职业生涯 致力于优化高胰岛素血症儿童的神经认知结果。

PROJECT SUMMARY/ABSTRACT The overall objective of this K23 application is to provide support for the additional training and experience that the principal investigator, a pediatric endocrinologist and epidemiologist, needs to develop an independent, patient-oriented research program in hyperinsulinism. Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infants and children. Onset of hypoglycemia in HI overlaps with a critical period of neurocognitive development that occurs in the first years of life. While children with HI are more likely to have neurocognitive deficits, little is known about the factors influencing trajectories of neurocognitive development in affected children. This project will: (1) identify neurocognitive trajectories in children with HI employing an accelerated longitudinal design, and (2) examine the relationship between timing of hypoglycemia exposure and neurocognitive outcomes through comparison of two clinical phenotypes of HI with natural variation in clinical course. To accomplish these aims a comprehensive neurocognitive battery will be administered at baseline and repeated at 1- and 2-years after baseline, to school-aged children with cured, focal HI (hypoglycemia exposure limited to early life), diffuse HI (early life and ongoing hypoglycemia exposure), and age, sex, and socioeconomic status matched healthy controls. The results of this project will fill critical gaps in knowledge about the impact of hyperinsulinemic hypoglycemia during periods of marked brain development and carry significant implications for clinical practice. This study may also have broad implications for other disorders associated with hyperinsulinemic hypoglycemia, including diabetes mellitus. The principal investigator will take full advantage of the rich scientific environment and outstanding resources afforded by the Children’s Hospital of Philadelphia and University of Pennsylvania to achieve her research and training goals. The proposal includes advanced training in longitudinal data analysis and longitudinal neurocognitive outcome assessment, which will be achieved through a combination of didactic coursework, practical research experience, and support form an expert, multidisciplinary mentorship and advisory team. The support of this K23 will enable the principal investigator to launch a successful career as an independent investigator dedicated to optimizing neurocognitive outcomes for children with hyperinsulinism.