Understanding, Predicting and Preventing Type 2 Diabetes in Youth, Boston Clinical Center (UPP Study)

了解、预测和预防青少年 2 型糖尿病，波士顿临床中心（UPP 研究）

• 批准号: 10583740
• 负责人: Amy Debra Fleischman
• 金额: $ 16.68万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-10 至 2029-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583740
• 关键词: Address; Adolescent; Adrenal Glands; Adult; Affect; Age; Androgens; Area; B-Lymphocytes; Basal metabolic rate; Beta Cell; Biological; Blood Vessels; Body Composition; Body mass index; Boston; COVID-19 pandemic; Cell physiology; Characteristics; Child; Childhood; Clinical; Clinical Research; Clinical assessments; Collaborations; Color; Communities; Continuous Glucose Monitor; Data; Data Collection; Detection; Development; Diabetes Mellitus; Diagnosis; Diet Surveys; Disease; Dual-Energy X-Ray Absorptiometry; Early Diagnosis; Environmental Risk Factor; Epigenetic Process; Evaluation; Evolution; Family history of; Fatty acid glycerol esters; Feces; Future; General Hospitals; Genomics; Geography; Glucose; Glycosylated hemoglobin A; Gonadal Hormones; Growth; Hair; Hand Strength; Hepatic; Home; Hormonal; Hormones; Hyperglycemia; Impairment; Incidence; Insulin Resistance; Insulin-Like Growth Factor I; Light; Massachusetts; Measurable; Measures; Mediator; Metabolic; Neighborhood Health Center; Neighborhoods; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Participant; Pathogenesis; Pediatric Hospitals; Peripheral Blood Mononuclear Cell; Phenotype; Physical activity; Physiological; Plasma; Prediabetes syndrome; Prevention; Puberty; Public Health; Research; Risk; Risk Factors; Risk Reduction; Running; Sampling; Shapes; Somatotropin; Stress; Systems Biology; Techniques; Testing; Triglycerides; Ultrasonography; Urine; VO2max; Visceral fat; Youth; actigraphy; biobank; blood glucose regulation; clinical center; cohort; community setting; data repository; diabetes pathogenesis; fasting plasma glucose; fitness; high body mass index; high risk; incretin hormone; indexing; insulin secretion; insulin sensitivity; macrovascular disease; marginalized community; marginalized population; metabolomics; modifiable risk; multiple omics; predictive marker; predictive modeling; prevent; progression marker; progression risk; recruit; remote assessment; repository; sample collection; social factors; social health determinants; trend; type 2 diabetes in children; ultrasound; waist circumference; wearable device

Project Summary / Abstract Rising obesity has led to an unprecedented increase in pre-diabetes (preD) and type 2 diabetes (T2D) incidence in children and adolescents, a worrisome trend amplified by the COVID 19 pandemic. Based on current evidence, it remains difficult to predict whether children and adolescents with preD will progress to T2D. Our proposal aims to address key questions in the pathogenesis of T2D, focusing on modifiable risk factors. Leveraging a collaboration between Boston Children’s Hospital, Joslin Diabetes Center, and Massachusetts General Hospital, in partnership with community health centers in the Greater Boston area, we propose to recruit a diverse cohort of early pubertal youth (ages 7-15, n=300) with preD, elevated BMI (≥95th percentile), a positive family history of diabetes, and one or more additional risk factors. We propose to combine rigorous annual clinical studies with convenient remote assessments, to gain a granular understanding of metabolic, hormonal and environmental factors contributing to T2D pathogenesis. In Aim 1, we will test whether measures of glucose homeostasis and beta cell function differ between youth with preD who progress to T2D versus those who revert to normoglycemia or remain preD. We propose to analyze glycemia and beta cell function using oral GTT and incretin hormone levels, and assessments adaptable to community settings, e.g., continuous glucose monitors and home A1c kits. In Aim 2, we will test whether fitness level and amount of physical activity differ between youth with preD who progress to T2D versus those who revert to normoglycemia or remain preD. We propose to evaluate fitness level using detailed clinical assessments, including VO2 max, assessments adaptable to community settings including grip strength, and free-living assessments using wearables and app-based activity tracking. In Aim 3, we will test whether evolution of body composition during growth and puberty predicts progression to T2D. We propose to analyze body composition (total and visceral fat) using DXA, and hepatic fat using echography-based assessments, gonadal hormones, adrenal androgens, and mediators of growth hormone action, as well as assessments adaptable to community settings, e.g., BMI and app-based dietary surveys. As secondary aims, we propose to create a data repository to allow evaluation of social and environmental factors contributing to T2D onset at a consortium level, with measures including social determinants of health, neighborhood and geographic characteristics (using geocoding techniques), and the environmental exposome. We also propose the creation of a biological repository to allow multi-omics studies to identify genomic, epigenetic, and/or metabolomic markers for progression from preD to T2D in youth at a consortium level. We propose to collect a rich biorepository of longitudinal samples (i.e., plasma, PBMCs, urine, stool, hair) from all participants that will set the stage for future systems biology-driven studies. Together, these studies will permit development of a predictive model based on variables easily measurable at the community level, which can then be applied to the detection and treatment of youth at highest risk of T2D.

项目摘要/摘要