Identifying Metabolic and Psychosocial Antecedents and Characteristics of youth-onset Type 2 diabetes (IMPACT DM)

项目摘要/摘要 青年2型糖尿病(YOT2D)的患病率每年以大约5%的速度增长， 对许多少数族裔/族裔群体的青年造成不成比例的影响。YOT2D是一个快速进步的 年轻人的疾病会导致许多终身健康并发症，从而增加发病率和 死亡率。研究表明，YOT2D进展的一个关键标志是β细胞的失败。到目前为止， 识别β细胞衰竭的预测因素，从而进展到YOT2D还没有阐明 早期干预和预防是不可能的。本提案的目标是确定新陈代谢和 青年起病的2型糖尿病(IMPACT DM)的心理社会因素和特征，是发展一种 全面的预测模型，将确定青少年患YOT2D的风险最高，设置 实施保护β细胞功能的预防策略的阶段。最重要的假设是一个 生理和心理社会因素的结合，特别是青春期、宫内暴露和心理社会因素 压力，是YOT2D发展的主要驱动力。该队列将包括那些风险最高的人 开发YOT2D，以便在生理、代谢和心理上对他们进行深入的表型 努力开发一个全面的预测模型。目标1将检查葡萄糖的动态平衡和 使用常规OGTT方法和自由生活连续血糖监测随时间变化的血糖 (CGM)。然后将使用这些测量来检查它们与β细胞功能的关系，该功能是 糖尿病进展识别预测YOT2D的关键血糖特征。目标2将确定生理学和 心理社会变量，如激素、心脏代谢健康、能量消耗、不良童年 事件(ACE)，以及宫内暴露，预测β细胞功能，从而预测YOT2D。更多新的预测值 YOT2D的研究将在目标3中进行，特别关注代谢组、微生物组和循环 MiRNA。使用这些新变量以及确定的血糖、生理和心理社会变量 在前面的目标中，将开发一个全面的模型来预测YOT2D。俄克拉荷马大学 健康科学中心(OUHSC)非常适合这项研究，因为它所服务的人群 (儿童肥胖率最高，拉美裔和美洲原住民最多，在全国排名第八 人口)，并建立了伙伴关系。在今天的试验中，俄克拉荷马临床中心招募了 保留的参与者比其他14个研究地点中的任何一个都多。总体而言，这项提议将导致 确定代谢和心理社会影响因素以及预测临床的特征 YOT2D的进展。此外，它还将确定影响β细胞功能的因素，从而导致发育 通过维持β细胞功能来预防YOT2D的干预措施，导致微血管减少 儿童期和成年期的并发症。

Project Summary / Abstract Youth onset type 2 diabetes (YOT2D) is increasing in prevalence by approximately 5% per year, and disproportionately impacts youth from many minority race/ethnic groups. YOT2D is a rapidly progressive disease in young adults leading to many life-long health complications resulting in increased morbidity and mortality. Research shows a key marker in the progression of YOT2D is failure of the β cells. To date, identifying predictors of β cell failure and thus the progression to YOT2D have not been elucidated making early intervention and prevention impossible. The goal of the present proposal, Identifying Metabolic and Psychosocial Antecedents and Characteristics of youth-onset Type 2 diabetes (IMPACT DM), is to develop a comprehensive prediction model that will identify youth at the highest risk of developing YOT2D setting the stage to implement prevention strategies preserving β cell function. The overarching hypothesis is that a combination of physiologic and psychosocial factors, specifically puberty, in utero exposures, and psychosocial stresses, are major drivers of the development of YOT2D. The cohort will include those at the highest risk of developing YOT2D in order to deeply phenotype them physically, metabolically, and psychosocially all in an effort to develop a comprehensive prediction model. Aim 1 will examine glucose homeostasis and changes in glycemia over time using conventional OGTT methods as well as free-living continuous glucose monitoring (CGM). These measures will then be used to examine their relationship to β cell function which is the driver of diabetes progression identifying key glycemic features that predict YOT2D. Aim 2 will identify physiologic and psychosocial variables such as hormones, cardiometabolic health, energy expenditure, adverse childhood events (ACEs), and in utero exposures that predict β cell function and thus YOT2D. Additional novel predictors of YOT2D will be examined in Aim 3, specifically focusing on metabolomic profiles, microbiome, and circulating miRNA. Using these novel variables as well as the glycemic, physiologic, and psychosocial variables identified in the previous aims, a comprehensive model to predict YOT2D will be developed. The University of Oklahoma Health Sciences Center (OUHSC) is exceptionally well-suited for this study because of the population served (8th in the nation for the highest rates of childhood obesity and substantial Hispanic and Native American populations), and established partnerships. In the TODAY trial, the Oklahoma clinical center recruited and retained more participants than any of the other 14 study sites. Overall this proposal will lead to the identification of metabolic and psychosocial antecedents and characteristics that predict the clinical progression of YOT2D. Also, it would identify factors impacting β cell function leading to the development interventions to prevent YOT2D through maintaining β cell function, resulting in the reduction of microvascular complications during childhood and young adulthood.