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

了解并针对青年发病 2 型糖尿病的病理生理学 - 生物统计学研究中心

基本信息

批准号：
10583114
负责人：
Ionut Bebu
金额：
$ 228万
依托单位：
GEORGE WASHINGTON UNIVERSITY
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：
2023-04-01 至 2028-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10583114
关键词：
Address Adolescent Adult Agreement Beta Cell Biometry Case Report Form Cell physiology Certification Characteristics Child Childhood Chronic stress Clinical Research Clinical Trials Collaborations Communication Complications of Diabetes Mellitus Conflict of Interest Consent Coupled Creativeness Data Deterioration Development Devices Diabetes Mellitus Enrollment Ensure Environmental Risk Factor Epidemiology Ethnic Origin Event Functional disorder Funding Future Gender Genetic Materials Goals Hormonal Incidence Infrastructure Institutional Review Boards Insulin Resistance Intention Intervention Laboratories Leadership Logistics Manuals Manuscripts Mediator Metabolic Methodology Methods Monitor Multicenter Studies National Institute of Diabetes and Digestive and Kidney Diseases Non-Insulin-Dependent Diabetes Mellitus Obesity Obesity Epidemic Observational Study Participant Pathogenesis Performance Persons Phenotype Physiological Physiology Population Characteristics Prediabetes syndrome Prevalence Prevention approach Prevention strategy Privatization Procedures Process Protocols documentation Puberty Publications Qualifying Quality Control Race Reporting Research Research Design Research Personnel Resources Risk Risk Factors Safety Serious Adverse Event Sex Differences Site Specific qualifier value Statistical Data Interpretation Statistical Methods System Training Translating Universities Validation Washington Youth adverse childhood events blood glucose regulation clinical research site cohort collaborative environment comparative effectiveness study data exchange data management diabetes control diabetes prevention program diabetes risk effective therapy ethnic diversity experience follow-up glycemic control high risk improved innovation insulin secretion insulin sensitivity meetings multidisciplinary novel operation preservation prevent primary outcome programs progression risk quality assurance racial diversity randomized trial recruit repository response secondary outcome sedentary lifestyle success timeline treatment strategy type 2 diabetes in children user-friendly virtual web site

项目摘要

Project Summary/Abstract Type 2 diabetes (T2D) in youth is increasingly prevalent in parallel with the obesity epidemic, yet effective treatment and prevention strategies are limited. The physiologic reduction in insulin sensitivity occurring during puberty in combination with obesity-related insulin resistance enhance the risk of T2D. Yet it remains unclear why some youth experience normal pubertal progression with intact β-cell function, while others do not, despite similar phenotypic and metabolic characteristics. The low incidence and prevalence of T2D in youth compared to adult’s turns the focus to identifying and characterizing pathophysiological precursors to T2D. More information is needed regarding the unique events during puberty to better understand the basic pathophysiology of glucose control, insulin sensitivity, β-cell function, and T2D risk in youth, as well as differences by sex/gender and race/ethnicity, and the potential contribution of harmful environmental factors that are characteristic of this population. Importantly, this research needs to address the timeline of pathophysiological activity from normoglycemia to prediabetes to youth-onset T2D (YO-T2D). The Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes (UTP-T2D) Consortium provides a unique opportunity to characterize the risk progression profile and mechanisms underlying the development of YO-T2D, and evaluate the effects of modifiable and non-modifiable risk factors. Ultimately, the results of this study will establish a basic pathophysiology to inform future studies aimed at achieving glycemic control, improving insulin sensitivity, preserving β-cell function, and/or preventing T2D in youth. To address this goal, the UTP-T2D study will recruit, enroll, and follow a large racially and ethnically diverse cohort of 3,000 at- risk obese youth in early puberty, extensively phenotype them as they transition through puberty, and characterize the course of decline and dysfunction in pathophysiological indicators that lead to T2D. The expected duration of the UTP-T2D study is 5 years, including planning, recruitment, follow-up, analysis, and reporting. In addition to addressing the aims with analyses conducted as part of the proposed study, the UTP- T2D consortium will store longitudinal biospecimens and genetic material with the intention of acquiring additional ancillary funding to pursue analysis of emerging indicators. The Biostatistics Research Center (BRC) will enhance the value of the UTP-T2D Consortium by 1) overseeing all operational aspects of the Consortium, 2) providing administrative resources and logical support of the Consortium, and 3) providing scientific and biostatistical expertise for the Consortium. Through effective organization, communication, and support, and by promoting a collaborative environment, the BRC will provide the framework and infrastructure for the Consortium to successfully recruit a cohort of early pubertal youth at risk for developing prediabetes and T2D, deeply phenotype them through puberty, and ultimately contribute to a better understanding of the pathophysiology of YO-T2D.

项目概要/摘要青少年 2 型糖尿病 (T2D) 与肥胖流行同时日益流行，但仍有效治疗和预防策略是有限的。青春期与肥胖相关的胰岛素抵抗相结合会增加患 T2D 的风险，但目前尚不清楚。为什么有些青少年会经历正常的青春期进展且具有完整的 β 细胞功能，而另一些青少年则不然，尽管相似的表型和代谢特征相比，青少年 T2D 的发病率和患病率较低。成人的重点转向识别和表征 T2D 的病理生理学前兆。需要了解青春期期间的独特事件，以更好地了解葡萄糖的基本病理生理学控制、胰岛素敏感性、β细胞功能和青少年 T2D 风险，以及性别和性别之间的差异种族/族裔，以及具有此特征的有害环境因素的潜在贡献重要的是，这项研究需要解决病理生理活动的时间表。血糖正常到糖尿病前期再到青年发病的 T2D (YO-T2D)。了解并针对青年发病 2 型糖尿病 (UTP-T2D) 联盟的病理生理学提供了一个独特的机会来描述风险进展状况和潜在的机制 YO-T2D 的开发，并评估可改变和不可改变的风险因素的影响。这项研究的结果将建立一个基本的病理生理学，为未来旨在实现血糖目标的研究提供信息控制、提高胰岛素敏感性、保留 β 细胞功能和/或预防青少年 T2D 来解决这个问题。目标，UTP-T2D 研究将招募、登记和跟踪一个由 3,000 名不同种族和族裔组成的大型队列—— 青春期早期青少年肥胖的风险，主要是在青春期过渡时对他们进行表型分析，以及描述导致 T2D 的病理生理指标下降和功能障碍的过程。 UTP-T2D研究预计持续5年，包括规划、招募、随访、分析和除了通过作为拟议研究的一部分进行的分析来解决目标之外，UTP- T2D 联盟将存储纵向生物样本和遗传物质，目的是获取更多用于对新指标进行分析的辅助资金。生物统计研究中心 (BRC) 将通过 1) 监督来增强 UTP-T2D 联盟的价值联盟的所有运营方面，2）为联盟提供行政资源和逻辑支持联盟，以及 3) 通过有效为联盟提供科学和生物统计专业知识。组织、沟通和支持，并通过促进协作环境，BRC 将提供联盟成功招募一批青春期早期青年的框架和基础设施患糖尿病前期和 T2D 的风险，通过青春期对它们进行深入的表型分析，并最终导致更好地了解 YO-T2D 的病理生理学。