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

项目总结 荟萃分析研究发现，患有精神分裂症的儿童在神经认知功能方面存在轻微但显著的缺陷。 1型糖尿病(T1D)与没有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，神经成像研究一致地观察到大脑结构的差异 以及T1D儿童的脑发育，特别是脑白质微结构。有证据表明 发病年龄、发病时的糖尿病酮症酸中毒(DKA)和长期接触 高血糖或严重低血糖可能会增加这些缺陷的风险或严重程度，但研究结果喜忧参半， 许多研究受到年龄较大的青少年或患有T1D的成年人、小样本或 横截面设计。因此，随着时间的推移，一项关于患有T1D的幼儿的大型前瞻性研究 需要严格的评估和跟踪，以确定可修改的风险和保护因素 这一人群中的神经认知并发症。这个U34规划奖将提供时间和资源 需要准备对患有T1D的幼儿(6至10岁)进行观察性纵向队列研究 在注册时)，以及没有糖尿病的儿童的对照组。我们将与其他公司签订合同 临床研究中心，获得制定神经成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名儿科医生 心理学家、儿科神经学家、儿科内分泌学家和儿科神经放射科专家； 成像科学和成像数据的协调，以及在分析方面经验丰富的生物统计学家 成像数据，以及研究人员使用一种基于手机的新方法来实时捕获儿童功能- 时间，称为生态瞬时评估。范德比尔特大学儿童糖尿病项目(CDP) 医疗中心为大量不同的T1D儿童提供服务，并具有强大的多中心历史 与其他儿科糖尿病中心的合作。拟议的项目将评估假设的风险因素。 (发病年龄、出现时的DKA和血糖控制)，以及潜在的可修改的保护因素 (儿童睡眠质量、照顾者痛苦和糖尿病设备的使用)。此外，我们还将优化成像 允许协调跨站点和扫描仪的神经成像数据的协议和处理工具 最可靠的分析。该项目有可能影响儿童的临床护理标准 T1D，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.