Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes

了解并针对青年发病 2 型糖尿病的病理生理学

基本信息

批准号：
10583335
负责人：
Micah Olson
金额：
$ 6.49万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-10 至 2029-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10583335
关键词：
Accelerometer Adolescence Adolescent Age Area Arizona Attention Behavior Behavioral Beta Cell Biological Biological Process Biology Blood specimen Cell physiology Characteristics Child Child health care Childhood Clinic Clinical Research Collection Communities Complex Continuous Glucose Monitor Cox Proportional Hazards Models Data Diabetes Mellitus Diabetes prevention Disease Disparity Dual-Energy X-Ray Absorptiometry Eating Ecological momentary assessment Education Endocrine Enrollment Environment Environmental Risk Factor Epigenetic Process Ethnic Origin Exposure to Family Family history of Fasting Fatty acid glycerol esters Functional disorder Funding Future Genetic Predisposition to Disease Genomics Health Health behavior Health behavior and outcomes Healthcare Systems Hepatic Hour Household Hyperglycemia Incidence Individual Insulin Resistance Life Low income Magnetic Resonance Imaging Modeling Morbid Obesity National Institute on Minority Health and Health Disparities Neighborhoods Non-Insulin-Dependent Diabetes Mellitus OGTT Obesity Organ Outcome Pancreas Participant PhenX Toolkit Phenotype Physical activity Physiological Physiology Poverty Prediabetes syndrome Predisposition Prevention program Process Puberty Race Research Research Personnel Restaurants Risk Risk Factors Sampling Science Services Single Parent Site Social Environment Structure of beta Cell of islet System Time United States National Institutes of Health Validation Visceral fat Vulnerable Populations Work Youth cohort community engagement contextual factors density design diabetes risk ethnic diversity ethnic minority population experience fast food glucose tolerance health determinants health equity high risk high risk population housing instability improved insulin secretion insulin sensitivity intergenerational medical specialties member metabolomics minority children novel marker population health prenatal exposure prevent prospective racial minority population recruit sex sleep pattern social social determinants social health determinants social influence sociodemographics structural determinants treatment program

项目摘要

ABSTRACT: Type 2 diabetes (T2D) in youth reduces quality and years of life. Disparities in T2D emerge early in life and disproportionately impact low-income and minority youth. T2D is the result of complex processes involving biological susceptibility and interdependent social, behavioral, and environmental factors that represent the root causes of disparities. Obesity, insulin resistance and pancreatic β-cell dysfunction have been the focus of many clinical studies aimed at understanding the pathophysiology of T2D in youth. However, multiple factors directly and indirectly contribute to risk including unhealthy behaviors, puberty, genetic predisposition, and epigenetic modulation. These additional factors are influenced by the social and environmental context that must but considered to advance our understanding of T2D in high-risk populations. Our transdisciplinary team has extensive experience understanding, preventing, and managing T2D among vulnerable and underrepresented youth. For over a decade, our research has been guided by a Community Advisory Board that has informed multiple NIH-funded studies focused on T2D in vulnerable populations. Our overall approach to T2D research is framed within an Expanded Ecodevelopmental Model that considers cultural, environmental, and social contexts that influence individual health behaviors and health outcomes during critical life periods. We will apply this model and leverage high-volume pediatric endocrine practice situated within one of the nation’s largest integrated pediatric healthcare systems to recruit a diverse sample of youth with obesity and prediabetes. To further support this work, we have developed a robust community engagement strategy to ensure that the research extends the available science AND advances towards health equity in the local community. Our transdisciplinary team is well-suited to contribute to a national consortium that identifies high-risk youth, understands the pathophysiology of T2D, and ultimately improves the health of this population. With this context, we propose the following Specific Aims: Specific Aim 1: Enroll, phenotype, and prospectively follow an ethnically diverse cohort of 6000 (400/site) children ages 8-14 with obesity and prediabetes. Specific Aim 2: Integrate free living assessments of glycemia and health behaviors. Specific Aim 3: Document family, social and environmental conditions that contribute to T2D risk. Specific Aim 4: Collect and bank fasting blood samples to support genomic and metabolomic analyses using validation and discovery approaches. Specific Aim 5: Examine the individual and potential interactive effects of biological, behavioral, and social determinants of T2D risk.

抽象的：青少年 2 型糖尿病 (T2D) 会降低生命质量并缩短生命年限。 T2D 对低收入和少数族裔青年的影响尤为严重，这是涉及复杂过程的结果。代表根源的生物易感性和相互依赖的社会、行为和环境因素肥胖、胰岛素抵抗和胰腺β细胞功能障碍一直是许多人关注的焦点。临床研究旨在了解青少年 T2D 的病理生理学，然而，多种因素直接影响。并间接导致风险，包括不健康行为、青春期、遗传倾向和表观遗传这些额外因素受到社会和环境背景的影响，但必须如此。我们的跨学科团队已被认为可以增进我们对高危人群中 T2D 的了解。在了解、预防和管理弱势和代表性不足的 T2D 方面拥有丰富的经验十多年来，我们的研究一直由社区咨询委员会指导，该委员会已向青年提供信息。 NIH 资助的多项研究重点关注易感人群的 T2D 我们的 T2D 研究总体方法。是在一个扩展的生态发展模型中构建的，该模型考虑了文化、环境和社会我们将应用影响生命关键时期个人健康行为和健康结果的环境。该模型并利用位于全国最大的儿科内分泌诊所之一的大量儿科内分泌实践整合儿科医疗保健系统，招募肥胖和糖尿病前期的不同青少年样本。为了进一步支持这项工作，我们制定了强有力的社区参与战略，以确保研究扩展了现有科学并促进当地社区的健康公平。跨学科团队非常适合为识别高风险青少年的国家联盟做出贡献，了解 T2D 的病理生理学，并最终改善该人群的健康。在此背景下，我们提出以下具体目标：具体目标 1：登记、表型分析并前瞻性追踪 6000 名不同种族的队列（400 人/中心） 8-14岁患有肥胖症和糖尿病前期的儿童。具体目标 2：整合血糖和健康行为的免费生活评估。具体目标 3：记录导致 T2D 风险的家庭、社会和环境条件。具体目标 4：收集并储存空腹血样，以支持使用以下方法进行基因组和代谢组学分析：验证和发现方法。具体目标 5：检查生物、行为和社会的个体和潜在交互影响 T2D 风险的决定因素。