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

先天性高胰岛素血症对整个学龄期神经认知功能轨迹的影响

• 批准号: 10723317
• 负责人: Elizabeth Rosenfeld
• 金额: $ 18.22万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723317
• 关键词: Acceleration; Address; Advisory Committees; Affect; Age; Applications Grants; Award; Biostatistical Methods; Blood Glucose; Brain; Characteristics; Child; Childhood; Clinical; Clinical Trials; Cognition; Data Analyses; Dedications; Development; Diabetes Mellitus; Diffuse; Disease; Endocrinologist; Environment; Epidemiologist; Epidemiology; Future; Goals; Growth; Hyperinsulinism; Hypoglycemia; Infant; Intervention; Knowledge; Life; Liquid substance; Longitudinal Studies; Measures; Mentored Patient-Oriented Research Career Development Award; Mentorship; Methods; Modeling; Neurocognitive; Neurocognitive Deficit; Outcome; Outcome Assessment; Outcome Measure; Patient-Focused Outcomes; Pattern; Pediatric Hospitals; Pennsylvania; Perinatal; Persistent Hyperinsulinemia Hypoglycemia of Infancy; Philadelphia; Physicians; Positioning Attribute; Principal Investigator; Research; Research Design; Research Personnel; Resources; Risk; School-Age Population; Scientist; Socioeconomic Status; Statistical Methods; Stress; Time; Training; United States National Institutes of Health; Universities; Variant; Work; aged; career; clinical phenotype; clinical practice; cognitive development; critical period; experience; improved; innovation; longitudinal design; multidisciplinary; neonatal period; patient oriented research; peer; primary outcome; programs; sex; skill acquisition

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.

项目概要/摘要 此 K23 应用程序的总体目标是为额外培训和经验提供支持， 主要研究者是一名儿科内分泌学家和流行病学家，需要建立一个独立的、 以患者为导向的高胰岛素血症研究项目是最常见的。 婴儿和儿童持续低血糖的原因与危重病中低血糖的发生重叠。 神经认知发育阶段发生在生命的最初几年，而患有 HI 的儿童更有可能发生。 存在神经认知缺陷，但对于影响神经认知轨迹的因素知之甚少 该项目将：(1) 确定患有 HI 的儿童的神经认知轨迹。 采用加速纵向设计，并且（2）检查时间之间的关系 通过比较 HI 的两种临床表型与低血糖暴露和神经认知结果 为了实现这些目标，将需要一个全面的神经认知电池。 在基线时对已治愈的学龄儿童进行治疗，并在基线后 1 年和 2 年重复进行 局灶性 HI（仅限于生命早期的低血糖暴露）、弥漫性 HI（生命早期和持续的低血糖） 暴露），以及与健康对照相匹配的年龄、性别和社会经济地位。该项目的结果将填补。 关于高胰岛素低血糖在显着脑损伤期间的影响的知识存在重大差距 的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。 用于与高胰岛素性低血糖相关的其他疾病，包括糖尿病。 研究者将充分利用研究所丰富的科研环境和优秀的资源 费城儿童医院和宾夕法尼亚大学帮助她实现了研究和培训目标。 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，将通过教学课程和实践研究相结合来实现 经验和支持形成了一个专家、多学科的指导和咨询团队。 K23 将使主要研究者能够作为独立研究者开启成功的职业生涯 致力于优化高胰岛素血症儿童的神经认知结果。