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

儿童 1 型糖尿病神经认知并发症的队列研究规划

• 批准号: 10020976
• 负责人: SIMONA GHETTI
• 金额: $ 35.22万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10020976
• 关键词: 10 year old; Adult; Aerobic Exercise; Affect; Age; Antibodies; Attention; Big Data; Biochemical; Biological Assay; Blood; Blood - brain barrier anatomy; Brain; Brain Chemistry; Brain Injuries; Child; Childhood diabetes; Chronic; Cognition; Cognitive; Cohort Studies; Complication; Data; Data Analyses; Data Science; Dementia; Diabetic Ketoacidosis; Diet; Disease Management; Elderly; Encephalitis; Enrollment; Equilibrium; Evaluation; Event; Exercise; Family dynamics; Feasibility Studies; Foundations; Functional disorder; Future; Glycosylated hemoglobin A; Hyperglycemia; Hypoglycemia; Image; Impaired cognition; Impairment; Individual; Inflammation; Inflammation Mediators; Inflammatory; Insulin-Dependent Diabetes Mellitus; Intervention; Lead; Life; Light; Link; Longitudinal Studies; Longitudinal cohort study; Machine Learning; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mediator of activation protein; Medicine; Memory; Mental Health; Methods; Multicenter Studies; Neurocognitive; Neuronal Injury; Newly Diagnosed; Nutrient; Onset of illness; Outcome; Outcome Measure; Patients; Persons; Phase; Physiological; Play; Procedures; Process; Protocols documentation; Quality of life; RNA; Research Design; Risk; Rodent Model; Role; Sample Size; Severities; Short-Term Memory; Siblings; Site; Sleep; Structure; Testing; Time; Work; cognitive ability; cognitive development; cognitive function; cognitive testing; cohort; computer infrastructure; cost; cytokine; dementia risk; diet and exercise; exosome; glycemic control; high risk; inflammatory marker; insulin dependent diabetes mellitus onset; long term memory; multidisciplinary; neuroinflammation; neuron loss; non-diabetic; nutrition; participant retention; preservation; prevent; primary outcome; prospective; relating to nervous system; secondary outcome; sleep quality; success

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.

项目摘要。 1型糖尿病（T1D）的儿童患有细微的认知障碍和结构性 大脑的改变。这些障碍随着年龄的增长而进展，最终可能导致难度增加 控制这种疾病，导致血糖控制恶化，潜在的威胁生命的并发症和 减少生活质量。 T1D认知能力下降的原因尚不清楚。情节 低血糖，慢性高血糖，血糖变异性和糖尿病性酮症酸中毒（DKA）均已 建议扮演角色。对与T1D认知能力下降有关的因素的了解加深了 负责这些关联的机制是必不可少的，使得保持认知的干预措施可以 提出。最近的数据表明，高血糖和DKA发作引起的神经炎症 可能在引起认知能力下降方面发挥着重要作用。也有证据表明，可修改的因素此类因素 作为营养，运动和睡眠质量可能会调节慢性神经炎症和影响的影响 认知结果。在这个项目中，我们将努力计划对因素的全面研究 与T1D儿童的认知有关。拟议的计划项目完成时，我们将 准备对新诊断的T1D儿童进行纵向队列研究。这项研究会 确定血糖控制和DKA暴露如何预测大脑结构和认知的改变，并建立 神经元损伤和炎症过程的标志是否可以解释这些纵向关系。建议的 评估将包括与T1D相关因素（血糖控制，血糖变异性，低血糖，DKA），大脑 结构和认知功能（注意，记忆和智商）。此外，我们将计划测量 使用血液测定的神经炎症的炎症介质和标志物（细胞因子测量， 外部分析，RNA微阵列）和评估可能改变炎症（例如饮食）的因素 （营养含量），睡眠质量和运动。为了优化研究设计，我们将利用 多学科团队开发研究方案，包括小儿糖尿病专家 发育，神经和系统性炎症，MR成像，营养，睡眠医学和数据科学。这 团队将共同努力确定协议，工作流和结果指标，并确定必要的 计算基础架构和数据分析策略。团队还将评估研究可行性（因素 影响协议的入学成功和公差），并确定必要的样本量 评估生化和成像措施的变异性。增加参与者的替代方法 将探索保留率，例如远程（在线）与人为认知测试的保留率。在此结束时 计划项目，我们将开发并优化了一项协议，以探索与认知相关的因素 T1D儿童的下降，为未来的研究奠定了旨在维护认知功能的基础。