Identifying Modifiable Risk and Protective Factors for Neurocognitive Complications of Pediatric Type 1 Diabetes

项目摘要 荟萃分析研究已经发现，在儿童神经认知功能的小，但显着的缺陷， 1型糖尿病（T1 D）与无糖尿病的同龄人相比，特别是在记忆，学习， 和执行功能技能。此外，神经影像学研究始终观察到大脑结构的差异 和脑发育，特别是脑白色物质的显微结构。证据表明 发病年龄、发病时的糖尿病酮症酸中毒（DKA）和暴露于慢性 高血糖症或严重低血糖症可能会增加这些缺陷的风险或严重性， 许多研究因纳入年龄较大的青少年或T1 D成人、样本量小或 横截面设计。因此，一项针对T1 D幼儿的大型前瞻性研究随着时间的推移， 需要进行严格的评估和随访，以确定可改变的风险和保护因素， 神经认知并发症这个U34规划奖将提供时间和资源 需要准备一项针对T1 D儿童（6 - 10岁）的观察性纵向队列研究 在登记时），以及无糖尿病儿童的对照组。我们将与其他公司签订合同， 临床研究中心，获得制定神经影像协调计划所需的数据，并最终确定 协议，包括神经成像和神经认知测试。我们的多学科团队包括一个儿科 心理学家、儿科神经学家、儿科内分泌学家和儿科神经放射学家; 成像科学和成像数据的协调，以及具有分析经验的生物统计学家， 成像数据，以及研究人员使用一种新的基于移动的手机的方法来捕捉儿童功能在真实的- 时间，称为生态瞬时评估。儿童糖尿病项目（CDP）范德比尔特大学 医疗中心服务于大量不同的T1 D儿童人群，并具有强大的多中心历史 与其他儿科糖尿病中心合作。拟议的项目将评估假设的风险因素 (age发病时的DKA和血糖控制），以及潜在的可改变的保护因素 （儿童睡眠质量、看护者痛苦和糖尿病设备的使用）。此外，我们将优化成像 协议和处理工具，以允许跨研究中心和扫描仪协调神经成像数据， 最强大的分析。该项目有可能影响儿童的临床护理标准， T1 D，并确定预防和干预的关键时期，以改善大脑健康和功能。

PROJECT SUMMARY Meta-analytic studies have identified small but significant deficits in neurocognitive functioning in children with type 1 diabetes (T1D) compared to their peers without diabetes, especially in the areas of memory, learning, and executive function skills. Further, neuroimaging studies consistently observe differences in brain structures and brain development in children with T1D, particularly brain white matter microstructure. Evidence suggests that factors such as age of onset, diabetic ketoacidosis (DKA) at time of onset, and exposure to chronic hyperglycemia or severe hypoglycemia may increase risk or severity of these deficits but findings are mixed, and many studies were limited by the inclusion of older adolescents or adults with T1D, small samples or cross-sectional designs. Thus, a large prospective study of young children with T1D followed over time with rigorous assessment and follow-up is needed to identify modifiable risk and protective factors for neurocognitive complications in this population. This U34 planning award will provide the time and resources needed to prepare for an observational, longitudinal cohort study of young children with T1D (age 6 to 10 years at enrollment), and a comparison group of children without diabetes. We will establish contracts with other clinical research centers, obtain data needed to develop neuroimaging harmonization plans, and finalize the protocols, including neuroimaging and neurocognitive testing. Our multidisciplinary team includes a pediatric psychologist, a pediatric neurologist, a pediatric endocrinologist, and a pediatric neuroradiologist; experts in imaging science and harmonization of imaging data, as well as a biostatistician experienced in analyses with imaging data, and a researcher using a novel mobile phone-based method to capture child function in real- time, called ecological momentary assessment. The Children's Diabetes Program (CDP) Vanderbilt University Medical Center serves a large, diverse population of children with T1D and has a strong history of multicenter collaborations with other pediatric diabetes centers. The proposed project will assess hypothesized risk factors (age of onset, DKA at presentation and glycemic control), as well as potentially modifiable protective factors (child sleep quality, caregiver distress, and use of diabetes devices). In addition, we will optimize imaging protocols and processing tools to allow for harmonization of neuroimaging data across sites and scanners for the most robust analysis. This project has the potential to influence standards of clinical care for children with T1D and to pinpoint critical periods for prevention and intervention to improve brain health and function.