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

项目总结/摘要 2型糖尿病（T2D）在年轻人中越来越普遍，与肥胖流行病平行，但有效 治疗和预防策略有限。胰岛素敏感性的生理性降低发生在 青春期与肥胖相关的胰岛素抵抗相结合增加了T2D的风险。但目前还不清楚 为什么有些年轻人经历正常的青春期进展，β细胞功能完整，而其他人则没有，尽管 相似的表型和代谢特征。青年T2D的低发病率和患病率 成人的转变的重点是识别和表征T2D的病理生理学前体。更多信息 为了更好地理解葡萄糖代谢的基本病理生理学， 控制，胰岛素敏感性，β细胞功能和青年T2D风险，以及性别/性别和 种族/民族，以及有害的环境因素的潜在贡献，这是特点 人口重要的是，这项研究需要解决的病理生理活动的时间轴， 糖尿病前期到青年发病型T2D（YO-T2D）。 青年发病2型糖尿病（UTP-T2D）联盟的理解和靶向病理生理学 提供了一个独特的机会，以表征风险进展概况和机制的基础上， YO-T2D的发展，并评估可改变和不可改变的风险因素的影响。最终 这项研究的结果将建立一个基本的病理生理学，以告知未来的研究，旨在实现血糖 控制，改善胰岛素敏感性，保留β细胞功能和/或预防青年T2D。为了解决这个 UTP-T2D研究的目标是招募、入组和随访一个大型的3,000名种族和民族多样化的队列， 在青春期早期有肥胖风险的青少年，在青春期过渡时广泛表现为表型， 表征导致T2D的病理生理学指标的下降和功能障碍的过程。的 UTP-T2D研究的预期持续时间为5年，包括计划、招募、随访、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实现目标外，UTP- T2D联盟将储存纵向生物标本和遗传物质， 提供辅助资金，以分析新出现的指标。 生物统计研究中心（BRC）将通过以下方式提高UTP-T2D联盟的价值：1）监督 联合体的所有业务方面，2）提供行政资源和逻辑支持， 3）为联盟提供科学和生物统计专业知识。通过有效 组织、沟通和支持，并通过促进协作环境，BRC将提供 该联盟成功招募一批青春期早期青年的框架和基础设施 发展为糖尿病前期和T2D的风险，通过青春期深入表型，并最终导致 更好地了解YO-T2D的病理生理学。

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.