Planning for a Cohort Study on Neurocognitive Complication of Type 1 Diabetes in Children

项目摘要。患有1型糖尿病（T1D）的儿童患有轻微的认知障碍和结构性疾病。 大脑的变化。这些损害随着年龄的增长而进展，最终可能导致困难增加 管理疾病，导致血糖控制恶化，可能危及生命的并发症，和 生活质量下降。T1D认知功能下降的原因尚不清楚。集 低血糖症、慢性高血糖症、血糖变异性和糖尿病酮症酸中毒（DKA）都已被 建议扮演角色。增加对与T1D认知能力下降相关因素的理解， 负责这些关联的机制是必不可少的，因此保护认知的干预措施可以 被提议。最近的数据表明，高血糖和DKA发作引起的神经炎症 可能是导致认知能力下降的主要原因。还有证据表明， 因为营养、运动和睡眠质量可能调节慢性神经炎症的影响， 认知结果。在这个项目中，我们将努力计划对影响环境的因素进行全面研究， 与T1D儿童的认知相关。在建议的规划项目完成后，我们会 准备对新诊断的T1D儿童进行纵向队列研究。本研究将 确定血糖控制和DKA暴露如何预测大脑结构和认知的改变， 神经元损伤和炎症过程的标志物是否可以解释这些纵向关系。提出 评估将包括T1D相关因素（血糖控制、血糖变异性、低血糖、DKA）、脑 结构和认知功能（注意力、记忆力和智商）。此外，我们将计划测量 使用血液分析的炎症介质和神经炎症标记物（细胞因子测量， 外泌体分析，RNA微阵列），并评估可能改变炎症的因素，如饮食 （营养成分）、睡眠质量和锻炼。为了优化研究设计，我们将利用 多学科团队制定研究方案，包括儿科糖尿病专家，认知 发展，神经和全身炎症，MR成像，营养，睡眠医学和数据科学。的 团队将共同完成方案、工作流程和结果措施，并确定必要的 计算基础设施和数据分析策略。该团队还将评估研究的可行性（因素 影响入组成功率和方案公差），并通过以下方式确定必要的样本量： 评价生物化学和成像测量的可变性。增加参与者的替代办法 还将探讨保留问题，如远程（在线）与面对面认知测试。在这一结论 规划项目，我们将开发和优化一个协议，以探索与认知相关的因素， T1D儿童的发病率下降，为未来旨在保护认知功能的研究奠定了基础。

Project Summary. Children with type 1 diabetes (T1D) suffer from subtle cognitive impairments and structural alterations in the brain. These impairments progress with age and may eventually lead to increased difficulty managing the disease, resulting in worsening glycemic control, potentially life-threatening complications, and reductions in quality of life. Causes of cognitive decline in T1D are not well understood. Episodes of hypoglycemia, chronic hyperglycemia, glycemic variability and diabetic ketoacidosis (DKA) have all been suggested to play roles. Increased understanding of factors linked to cognitive decline in T1D, and the mechanisms responsible for these associations, is essential such that interventions to preserve cognition could be proposed. Recent data suggest that neuroinflammation resulting from hyperglycemia and episodes of DKA may be play a prominent role in causing cognitive decline. There is also evidence that modifiable factors such as nutrition, exercise, and sleep quality might modulate effects of chronic neuroinflammation and influence cognitive outcomes. In this project, we will engage in efforts to plan a comprehensive study of factors associated with cognition in children with T1D. At the completion of the proposed planning project, we will be prepared to conduct a longitudinal cohort study of children with newly diagnosed T1D. This study will determine how glycemic control and DKA exposure predict altered brain structure and cognition and establish whether markers of neuronal injury and inflammatory processes explain these longitudinal relations. Proposed assessments will include T1D-related factors (glycemic control, glycemic variability, hypoglycemia, DKA), brain structure and cognitive function (attention, memory and IQ). In addition, we will plan measurements of inflammatory mediators and markers of neuroinflammation using blood assays (cytokine measurements, exosome analyses, RNA microarrays), and evaluate factors that might modify inflammation such as diet (nutrient content), sleep quality and exercise. To optimize the study design, we will utilize the expertise of a multidisciplinary team to develop the study protocol, including experts in pediatric diabetes, cognitive development, neural and systemic inflammation, MR imaging, nutrition, sleep medicine, and data science. The team will work together to finalizing the protocol, work-flow and outcome measures, and identify the necessary computational infrastructure and data analysis strategies. The team will also assess study feasibility (factors affecting enrollment success and tolerance of the protocol) and determine necessary sample size by evaluating variability in biochemical and imaging measures. Alternative approaches to increase participant retention, such as remote (online) versus in person cognitive testing, will be explored. At the conclusion of this planning project, we will have developed and optimized a protocol to explore factors associated with cognitive decline in children with T1D, laying a foundation for future studies aimed at preserving cognitive function.