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

• 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
• 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

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.

项目摘要/摘要 青年中2型糖尿病（T2D）与肥胖流行同行越来越普遍 治疗和预防策略有限。胰岛素敏感性的生理降低在 青春期与肥胖相关的胰岛素抵抗结合增强了T2D的风险。但还不清楚 为什么有些青年会以完整的β细胞功能经历正常的青春期进展 相似的表型和代谢特征。与年轻人相比 成年人的重点是识别和表征T2D的病理生理前体。更多信息 对于青春期期间的独特事件，需要更好地了解葡萄糖的基本病理生理学 年轻人的控制，胰岛素敏感性，β细胞功能和T2D风险以及性别/性别的差异 种族/种族以及有害环境因素的潜在贡献 人口。重要的是，这项研究需要解决从 糖尿病到青年发作的T2D（YO-T2D）的正常血糖。 对青年2型糖尿病（UTP-T2D）财团的病理生理学的理解和靶向 提供了一个独特的机会来表征风险进度概况和基础机制 开发YO-T2D，并评估可修改和不可修改的危险因素的影响。最终， 这项研究的结果将建立基本的病理生理学，以告知未来的研究，以实现血糖 控制，提高胰岛素敏感性，保留β细胞功能和/或预防青年的T2D。解决这个问题 目标是，UTP-T2D研究将招募，注册和遵循大约3,000个大致和种族多样的队列 冒险在青春期初期肥胖青年，在过渡青春期过渡时广泛表型，并且 表征导致T2D的病理生理指标的下降和功能障碍。这 UTP-T2D研究的预期持续时间为5年，包括计划，招聘，后续，分析和 报告。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财团将存储纵向生物测量和遗传物质，以获取更多 辅助资金以追求新兴指标的分析。 生物统计研究中心（BRC）将通过1）监督UTP-T2D联盟的价值 财团的所有运营方面，2）提供行政资源和逻辑支持 财团和3）为财团提供科学和生物统计学专业知识。通过有效 组织，沟通和支持，通过促进协作环境，BRC将提供 财团的框架和基础设施成功地招募了一群青年早期青年队 出现糖尿病前和T2D的风险，通过青春期深层表型，并最终有助于 更好地了解YO-T2D的病理生理学。