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.

项目摘要 /摘要青年发病2型糖尿病（YOT2D）每年的患病率增加了约5％，并且不成比例地影响许多少数族裔/族裔群体的青年。 yot2d是一个快速进步的年轻人的疾病导致许多终身健康并发症，导致发病率增加和死亡。研究表明，YOT2D进展的关键标记是β细胞的失败。迄今为止，尚未阐明β细胞衰竭的预测因子，因此尚未阐明YOT2D的进展早期干预和预防不可能。本提案的目标，确定代谢和青少年2型糖尿病（影响DM）的心理心理前因和特征是发展全面的预测模型将确定有开发Yot2D风险最高风险的年轻人实施保存β细胞功能的预防策略的阶段。总体假设是生理和社会心理因素，特别是青春期的结合，在子宫曝光和社会心理中的结合压力是Yot2d发展的主要驱动力。该队列将包括最高风险的人为了在身体，代谢和心理上对它们进行深层表型的发展，努力开发全面的预测模型。 AIM 1将检查葡萄糖稳态和变化随着时间的流逝，使用常规的OGTT方法以及自由活动的连续葡萄糖监测（CGM）。然后，这些措施将用于检查它们与β细胞功能的关系，这是糖尿病进展鉴定了预测Yot2d的关键血糖特征。 AIM 2将确定生理学和心理社会变量，例如激素，心脏代谢健康，能量消耗，不利的童年事件（ACE），以及在预测β细胞功能并因此yot2d的子宫暴露中。其他新颖的预测因子 YOT2D的of将在AIM 3中进行检查，专门针对代谢组轮廓，微生物组和循环 mirna。使用这些新型变量以及确定的血糖，生理和心理社会变量在上一个目标中，将开发一个预测YOT2D的综合模型。俄克拉荷马大学健康科学中心（OUHSC）非常适合这项研究（以最高的儿童肥胖和大量西班牙裔和美洲原住民的速度，全国第八人口），并建立了伙伴关系。在今日试验中，俄克拉荷马州临床中心招募和保留比其他14个研究站点中的任何一个。总的来说，这一建议将导致鉴定代谢和社会心理的先例和特征，这些预测临床 yot2d的进展。此外，它将确定影响β细胞功能的因素，导致发展通过维持β细胞功能来防止YOT2D的干预措施，导致微血管降低童年和成年时期的并发症。