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

确定青年发病 2 型糖尿病 (IMPACT DM) 的代谢和心理社会因素和特征

• 批准号: 10584028
• 负责人: Jeanie Beatrice Tryggestad
• 金额: $ 5.55万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-23 至 2029-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584028
• 关键词: Address; Adolescent; Affect; Algorithms; Beta Cell; Biochemical; Biological Markers; Biological Specimen Banks; Body Composition; C-Peptide; Cell physiology; Central obesity; Characteristics; Child; Childhood; Chronic stress; Complications of Diabetes Mellitus; Continuous Glucose Monitor; Development; Diabetes Mellitus; Diagnosis; Disease; Disease Progression; Early Intervention; Energy Metabolism; Environment; Ethnic Origin; Ethnic Population; Failure; Fatty acid glycerol esters; Fructosamine; Glucose; Glycosylated hemoglobin A; Goals; Health; Health Sciences; High Density Lipoprotein Cholesterol; Hispanic Americans; Hormones; Hour; Hydrocortisone; Hypertension; Insulin; Intervention; Measurable; Measures; Mediating; Mental Depression; Metabolic; Methods; MicroRNAs; Microvascular Dysfunction; Modeling; Morbidity - disease rate; Native Americans; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Oklahoma; Pancreas; Participant; Patient Recruitments; Pattern; Pharmacologic Substance; Phenotype; Physiological; Population; Prediabetes syndrome; Predictive Value; Pregnancy; Prevalence; Prevention; Prevention strategy; Progressive Disease; Proinsulin; Proteins; Psychosocial Factor; Psychosocial Stress; Puberty; Records; Regression Analysis; Research; Rest; Risk; Risk Factors; Salivary; Serum; Site; Testing; Time; Treatment Failure; Universities; Youth; adipokines; adverse childhood events; blood glucose regulation; cardiometabolism; circulating microRNA; clinical center; clinical predictors; cohort; cytokine; deprivation; design; exercise capacity; experience; fasting glucose; gut microbiome; high risk; in utero; indexing; macrovascular disease; maternal obesity; metabolomics; microbiome; minority children; mortality; novel; novel marker; obesity in children; patient retention; predictive modeling; prenatal exposure; preservation; prevent; psychosocial; psychosocial stressors; racial minority; racial minority population; recruit; socioeconomics; therapy development; time use; treatment optimization; young adult

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.

项目总结/摘要 青年发病2型糖尿病（YOT 2D）的患病率每年增加约5%， 对许多少数种族/族裔群体的青年产生了不成比例的影响。YOT 2D是一个快速发展的 青年人的疾病导致许多终身健康并发症，导致发病率增加， mortality.研究表明，YOT 2D进展的一个关键标志是β细胞的衰竭。到目前为止， 确定β细胞衰竭的预测因素，因此尚未阐明向YOT 2D的进展， 早期干预和预防不可能。本提案的目标，确定代谢和 青年发病2型糖尿病的心理社会因素和特征（IMPACT DM），是制定一个 一个综合预测模型，将确定青年在发展YOT 2D的最高风险， 阶段，以实施保护β细胞功能的预防策略。总体假设是， 生理和社会心理因素的结合，特别是青春期、子宫内暴露和社会心理因素 是YOT 2D发展的主要驱动力。该队列将包括那些风险最高的人， 发展YOT 2D，以便在身体，代谢和心理社会方面深入表现他们， 努力建立一个全面的预测模型。目标1将检查葡萄糖稳态和 使用传统OGTT方法以及自由生活连续血糖监测随时间推移而变化 （CGM）。然后，这些测量将用于检查它们与β细胞功能的关系，β细胞功能是 糖尿病进展确定预测YOT 2D的关键血糖特征。目标2将确定生理和 社会心理变量，如激素、心脏代谢健康、能量消耗、不良童年 事件（ACE）和子宫内暴露，预测β细胞功能，从而预测YOT 2D。其他新的预测因素 将在目标3中检查YOT 2D的水平，特别关注代谢组学特征、微生物组和循环 小RNA。使用这些新的变量以及血糖，生理和心理社会变量确定 在先前的目标中，将开发一个预测YOT 2D的综合模型。俄克拉荷马州大学 健康科学中心（OUHSC）非常适合这项研究，因为它所服务的人群 (8th美国儿童肥胖率最高， 人口），并建立了伙伴关系。在TODAY试验中，俄克拉荷马州临床中心招募了 比其他14个研究中心保留了更多的参与者。总的来说，这项建议将导致 确定代谢和心理社会的前因和特征，预测临床 YOT 2D的发展此外，它还将确定影响β细胞功能导致发展的因素 通过维持β细胞功能预防YOT 2D的干预措施，导致微血管减少 儿童期和青年期的并发症。