Identifying lifelong factors that impact brain health and outcomes in type 1 diabetes: The Cognition and Longitudinal Assessments of Risk Factors over 30 Years (CLARiFY) Diabetes Complications Study

确定影响 1 型糖尿病大脑健康和结果的终生因素：30 年来风险因素的认知和纵向评估 (CLARiFY) 糖尿病并发症研究

• 批准号: 10665709
• 负责人: Richard Beare
• 金额: $ 46.51万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665709
• 关键词: 6 year old; Acute; Adult; Adverse effects; Age; Belief; Blood Vessels; Brain; Cerebrum; Child; Childhood; Childhood diabetes; Chronic; Clinical; Clinical Management; Cognition; Cognitive; Cognitive deficits; Cohort Studies; Community Health; Complications of Diabetes Mellitus; Cross-Sectional Studies; Data; Data Collection; Diabetes Mellitus; Diabetic Ketoacidosis; Diagnosis; Disease; Disease susceptibility; Educational Intervention; Exhibits; Exposure to; Future; Glycosylated hemoglobin A; Goals; Growth; Health; Hyperglycemia; Hypoglycemia; Impaired cognition; Incidence; Individual; Insulin-Dependent Diabetes Mellitus; Knowledge; Life; Life Cycle Stages; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Metabolic; Microvascular Dysfunction; Morbidity - disease rate; Outcome; Participant; Pediatric Hospitals; Perfusion; Population; Predisposition; Prevalence; Prospective Studies; Public Health; Recording of previous events; Research; Risk; Risk Assessment; Risk Factors; Stratification; Testing; Time; Well in self; Work; Youth; brain health; brain volume; cognitive change; cognitive function; cognitive performance; cognitive retraining; cognitive skill; cohort; cost; design; early childhood; emerging adult; evidence base; follow-up; functional outcomes; individualized medicine; insulin dependent diabetes mellitus onset; longitudinal analysis; macrovascular disease; magnetic resonance imaging biomarker; neurodevelopment; neurotoxic; neurotoxicity; prepuberty; preservation; prevent; prospective; resilience factor; treatment strategy

ABSTRACT Type 1 diabetes (T1D) is associated with brain and cognition changes as well as well-documented longer-term micro- and macrovascular complications. The impact of brain changes and cognitive deficits on functional out- comes, however, is less clear, and most current data relates to T1D youth. Thus, T1D is associated with signif- icant health and functional morbidity, and in addition to personal costs, community and public health burden is significant and likely increasing in line with the rising global T1D prevalence. Much current information about T1D outcomes is derived from cross-sectional or longitudinal studies with short follow-up periods. These have provided rich data about the short-term T1D impact on individuals, but have an inability to discern causal asso- ciations and longer-term effects. Longitudinal studies examining within-individual changes in brain and cogni- tion over time are required to better define specific risk and resilience factors that influence long-term out- comes. The Royal Children’s Hospital (RCH) diabetes cohort study is the only prospective study of individuals with T1D from childhood diagnosis through adulthood, with four previous waves of data collection. At baseline, participants with T1D did not differ from healthy controls on IQ, specific cognitive skills, or emotional well-being. Subsequent waves of data collection documented structural and functional brain changes, cognitive decre- ments, and poorer functional outcome in T1D compared to healthy controls into early adulthood. We now pro- pose a further follow-up of this cohort, the CLARiFY study (The Cognition and Longitudinal Assessments of Risk Factors over 30 Years (CLARiFY) Diabetes Complications Study), to document brain, cognition, and func- tional outcomes in mid-adult life ~30 years after T1D onset. We will use longitudinal data from the current study and from previous waves of data collection to identify which glycemic insults are most detrimental to the brain/cognition and at which age/stage of neurodevelopment. The following specific hypotheses will be tested: 1) in cross-sectional analyses, T1D subjects will have lower brain volumes, lower cognitive scores, and poorer functional outcomes at middle adulthood than non-T1D subjects, and in longitudinal analyses, T1D subjects will exhibit a greater decline in cognitive performance that associates with greater MRI differences at middle adulthood, and greater change in MRI brain volumes from 12 years to 30 years post-diagnosis; and 2) hyper- glycemia in childhood (<18 years) will be the strongest dysglycemic determinant of brain health in mid-adult life. Further, the association between pre-pubertal hyperglycemia and brain outcomes will be most pronounced in those with (a) T1D onset at <6 years of age; (b) severe hypoglycemia and/or DKA episodes after early expo- sure to hyperglycemia, and (c) evidence of extra-cerebral microvascular and/or macrovascular disease in mid- adult life. An empirically based stratification of glycemic neurotoxic ‘risk’ as it varies across the life cycle would allow clinicians to offer optimal clinical management designed to both achieve good metabolic outcomes while at the same time protecting the developing brain and preserving cognitive function.

抽象的 1型糖尿病（T1D）与大脑和认知变化以及有据可查的长期有关 微血管并发症。大脑变化和认知缺陷对功能外的影响 但是，来了，不太清楚，大多数当前数据与T1D青年有关。那，t1d与显着相关 ICANT的健康和功能性发病率，除了个人成本外，社区和公共卫生伯恩是 与全球T1D流行率上升相符的显着且可能增加。关于有关的许多有关有关的信息 T1D结果来自横断面或纵向研究，随访时间短。这些有 提供了有关短期T1D对个体影响的丰富数据，但无法辨别因果关系 阳离子和长期影响。纵向研究检查了大脑和认知的个体内部变化 随着时间的流逝，需要更好地定义特定的风险和弹性因素，这些风险和弹性因素影响长期的外观 来。皇家儿童医院（RCH）糖尿病队列研究是个人的唯一前瞻性研究 从儿童期诊断到成年期的T1D，有四个以前的数据收集浪潮。基线， 具有T1D的参与者与智商，特定认知能力或情感健康的健康对照没有差异。 随后的数据收集波记录了结构性和功能性大脑的变化，认知衰落 与成年初期的健康对照相比，T1D的晶状体和功能效果较差。我们现在支持 澄清研究（认知和纵向评估 30年以来的危险因素（澄清）糖尿病并发症研究），以记录大脑，认知和功能 T1D发作后30年，成年生活中的结局。我们将使用当前研究的纵向数据 从以前的数据收集浪潮中，以确定哪些血糖损伤最有害于 大脑/认知以及神经发育的年龄/阶段。将测试以下特定假设： 1）在横断面分析中，T1D受试者的脑量较低，认知评分较低，较差 成年中期的功能结果比非T1D受试者，在纵向分析中，T1D受试者 在中间的MRI差异与更大的MRI差异相关的认知表现下降将更大 成年，MRI脑体积从诊断后的12年增加到30年； 2）超级 儿童时期（<18岁）将是成年后大脑健康的强大性血糖决定剂 生活。此外，预伯伯尔前高血糖和大脑结果之间的关联将最为明显 在（a）T1D发作的人中，年龄在6岁时； （b）早期博览会后严重的低血糖和/或DKA发作 一定要高血糖，以及（c）中脑外微血管和/或大血管疾病的证据 成人生活。基于经验的血糖神经毒性“风险”随着生命周期的变化而变化 允许临床医生提供最佳的临床管理，旨在实现良好的代谢结果 同时保护发展中的大脑并保留认知功能。