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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要青少年发病的 2 型糖尿病 (YOT2D) 患病率每年增加约 5%，并且 YOT2D 对许多少数族裔/族裔群体的青少年产生了不成比例的影响。年轻人的疾病会导致许多终生健康并发症，从而导致发病率增加和迄今为止，研究表明 YOT2D 进展的一个关键标志是 β 细胞的衰竭。 β 细胞衰竭的预测因子以及因此进展为 YOT2D 的预测因子尚未阐明本提案的目标是识别代谢和预防。青年发病 2 型糖尿病 (IMPACT DM) 的心理社会前因和特征综合预测模型将确定发展 YOT2D 风险最高的青少年，并设定阶段实施保护 β 细胞功能的预防策略。生理和心理社会因素的结合，特别是青春期、子宫内暴露和心理社会因素压力是 YOT2D 发展的主要驱动力，该群体将包括那些面临最高风险的人。开发 YOT2D，以便在身体、代谢和社会心理方面深入了解他们的表型努力开发一个全面的预测模型，目标 1 将检查葡萄糖稳态和变化。使用传统 OGTT 方法以及自由生活连续血糖监测随时间变化的血糖 (CGM) 然后将使用这些措施来检查它们与β细胞功能的关系，β细胞功能是β细胞功能的驱动因素。糖尿病进展，识别预测 YOT2D 的关键血糖特征，目标 2 将识别生理和血糖特征。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），以及预测 β 细胞功能的子宫内暴露，从而预测 YOT2D。 YOT2D 的研究将在目标 3 中进行检查，特别关注代谢组学概况、微生物组和循环 miRNA。使用这些新变量以及已确定的血糖、生理和心理变量。在之前的目标中，俄克拉荷马大学将开发一个预测 YOT2D 的综合模型。健康科学中心 (OUHSC) 由于所服务的人群而非常适合这项研究（儿童肥胖率最高，西班牙裔和美洲原住民比例居全国第八位）人口），并在今日试验中建立了合作伙伴关系，俄克拉荷马州临床中心招募并建立了合作伙伴关系。总体而言，该提案将导致比其他 14 个研究中心保留更多的参与者。识别代谢和心理社会因素以及预测临床的特征此外，它还将确定影响导致发育的 β 细胞功能的因素。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青年期的并发症。