Brain Health Across the Metabolic Continuum in Youth at Risk for T2D

患有 T2D 风险的青少年整个代谢连续体的大脑健康

基本信息

批准号：
10488062
负责人：
SILVA A ARSLANIAN
金额：
$ 64.15万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-11 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10488062
关键词：
Address Adolescent Adult Affect Age Aggressive course Alzheimer&apos s disease risk American Beta Cell Blood Vessels Body mass index Brain Cell physiology Cerebrovascular Circulation Child Clinical Cognition Cognitive Delayed Memory Developmental Process Diagnosis Diffusion Disease Ethnic Origin Functional disorder Funding Goals Hippocampus (Brain)Hyperglycemia Impaired cognition Impairment Inflammation Insulin Resistance Insulin deficiency Intervention Knowledge Lead Magnetic Resonance Imaging Measures Metabolic Metabolic dysfunction Microvascular Dysfunction National Institute of Diabetes and Digestive and Kidney Diseases Nature Non-Insulin-Dependent Diabetes Mellitus Obesity Outcome Overweight Persons Physiological Predictive Factor Prevalence Public Health Race Reporting Research Risk Risk Factors Socioeconomic Status Statistical Models Structure Time Weight Youth arterial spin labeling body system brain health cognitive testing early onset early-onset obesity executive function follow-up glucose tolerance impaired glucose tolerance insulin secretion lifetime risk neurodevelopment neuroinflammation processing speed sex spectrograph systemic inflammatory response white matter

项目摘要

Type 2 diabetes mellitus (T2D) is a significant public health problem affecting ~30 million American. Obesity, insulin resistance, insulin deficiency (β cell dysfunction) and dysglycemia all precede the diagnosis of T2D and are known to promote inflammation and ultimately lead to microvascular complications. More recently, research has identified brain-related complications in adult-onset T2D, including reduced regional brain structure and function, impaired cognition, and increased lifetime risk for Alzheimer’s disease. Alarmingly, an increasing number of children and adolescents are being diagnosed with T2D, likely due to the growing prevalence and earlier onset of obesity. Youth-onset T2D appears to have a more aggressive course than adult-onset T2D, with earlier onset and more rapid progression of microvascular complications. In addition, studies of youth with obesity and youth-onset T2D have reported robust differences in regional brain structure and cognition, suggesting that brain effects may follow the same aggressive course as the more typical vascular complications. Unfortunately, little is known about the factors associated with poor brain structure and function in youth with T2D. To address this critical gap in knowledge, we propose to study youth across the spectrum of body mass index (BMI) and metabolic dysfunction. This approach will allow us to disentangle the relationship of key features of T2D risk (e.g. obesity) with intermediary physiologic changes that pose a risk for the brain (e.g. insulin resistance, inflammation, β-cell dysfunction and dysglycemia) that may lead to reduced brain structure and function in T2D. We will determine which of these factors are most associated with differences in brain structure and function among groups, over time, and how these effects differ from normal neurodevelopment. Given that the disease occurs at a time when brains are undergoing dramatic developmental processes, the aggressive nature of youth-onset T2D progression and complications in other organ systems, these results may provide guidance and justification for longer follow-up, interventional or mechanistic studies and have important clinical implications.

2 型糖尿病 (T2D) 是影响约 3000 万美国人的重大公共卫生问题。胰岛素抵抗、胰岛素缺乏（β 细胞功能障碍）和血糖异常均先于 T2D 诊断，最近的研究表明，它们会促进炎症并最终导致微血管并发症。已经确定了成人发病的 T2D 中与大脑相关的并发症，包括区域大脑结构减少和功能、认知受损以及终生罹患阿尔茨海默病的风险增加。大量儿童和青少年被诊断患有 T2D，这可能是由于患病率不断上升以及青少年发病的 T2D 似乎比成人发病的 T2D 具有更严重的病程。此外，针对青少年的研究表明，微血管并发症发病较早且进展较快。据报道，肥胖和青年发病的 T2D 在区域大脑结构和认知方面存在巨大差异，这表明大脑效应可能与更典型的血管并发症具有相同的侵袭性过程。不幸的是，我们对与青少年大脑结构和功能不良相关的因素知之甚少。为了解决这一关键的知识差距，我们建议研究青少年的各个体重范围。这种方法将使我们能够理清关键特征的关系。 T2D 风险（例如肥胖）与对大脑构成风险的中间生理变化（例如胰岛素抵抗力、炎症、β细胞功能障碍和血糖异常）可能导致大脑结构减少和我们将确定哪些因素与大脑结构差异最相关。随着时间的推移，群体之间的功能以及这些影响与正常神经发育有何不同。这种疾病发生在大脑正在经历戏剧性的发育过程时，攻击性的这些结果可能提供青少年发病的 T2D 进展和其他器官系统并发症的性质为长期随访、介入或机制研究提供指导和理由，并具有临床重要意义影响。