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The PRIORITY Study: from PRedIctiOn to pReventIon of youth-onset TYpe 2 diabetes

优先研究：从预测到预防青少年发病的 2 型糖尿病

基本信息

批准号：
10583291
负责人：
SHEELA NATESH MAGGE
金额：
$ 6.38万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2023-02-22 至 2029-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10583291
关键词：
13 year old 14 year old Adolescent Adult Adult Children Affect African ancestry Age Asian B-Lymphocytes Baltimore Behavioral Beta Cell Black Populations Black race Blood Pressure Body Composition Body mass index Cardiovascular system Cell physiology Cell secretion Child Childhood Chronic stress Clinic Clinical Research Clinical Trials Communities Continuous Glucose Monitor Coupled Development Diagnosis Diet Disease Dual-Energy X-Ray Absorptiometry Early treatment Education Endocrinology Enrollment Epigenetic Process Ethnic Origin European ancestry Failure Family Family history of Fatty Liver Fatty acid glycerol esters Florida Functional disorder Future Genetic Glucagon Glucose Glycosylated hemoglobin A Health system Hepatic High Density Lipoproteins Hispanic Hispanic Populations Hour Impaired fasting glycaemia Impairment Incidence Income Inflammatory Insulin Insulin Resistance Kinetics Learning Life Lipids Longitudinal cohort Low income Measures Metabolic Metformin Methodology Microvascular Dysfunction Minority Minority Groups Minority Health Research Modeling Morbidity - disease rate Neighborhoods Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Not Hispanic or Latino OGTT Obesity Outcome Overweight Pacific Islander Parents Patient Self-Report Pharmacotherapy Phenotype Physical activity Physiological Prediabetes syndrome Prevalence Prevention Prevention strategy Primary Care Puberty Public Health Race Recording of previous events Risk Risk Factors Site Source South Asian Techniques Testing Treatment Failure Trust Visceral Youth adipokines adverse childhood events boys cardiovascular risk factor care providers children of color clinically relevant cohort depressive symptoms diabetes prevention program diabetes risk early onset ethnic diversity ethnic minority experience fasting glucose fitness genetic risk factor girls health care availability health care disparity high school impaired glucose tolerance improved in vivo innovation mathematical model metabolic phenotype minority children multidisciplinary neighborhood disadvantage novel obesity in children pandemic disease particle pediatrician predictive modeling preservation progression risk racial diversity racial minority recruit retention rate risk variant social social health determinants socioeconomic disadvantage socioeconomic disparity socioeconomics statistics stressor treatment strategy trustworthiness

项目摘要

Project Summary/Abstract Increases in pediatric obesity have led to an increased burden of youth-onset (Yo) type 2 diabetes (T2D), disproportionately affecting vulnerable youth. YoT2D is characterized by extreme insulin resistance, insulin hypersecretion, rapid b cell failure, and increased complications compared to adult T2D, raising concern for significant morbidity very early in life. However, the mechanism(s) and risk factors that cause some adolescents with prediabetes (PreDM) to progress to YoT2D while others do not, remain poorly understood. This proposal will study early pubertal youth at risk for YoT2D, to develop more precise prediction paradigms of progression to YoT2D, and to investigate pathophysiologic drivers. YoT2D disproportionately affects racial and ethnic minorities, often with multiple socioeconomic stressors, and the impact of social determinants of health (SDoH) on progression to YoT2D must be clarified. Dr. Sheela N. Magge (PI) has assembled a highly- experienced team from Johns Hopkins sites in Baltimore and Florida, including primary care pediatricians (Perrin, Polk, Showell, Hernandez) at clinics serving large Black and Hispanic populations with socioeconomic disadvantage. Participation in research by minoritized groups is influenced by the trustworthiness of the health system, and study recruitment will be aided by leveraging these trusted care providers. Dr. Magge proposes an innovative approach, recruiting from 3 distinct sources: 1. pediatric subspecialty clinics (endocrinology and obesity), 2. general pediatric clinics serving low-income children of color, and 3. offspring of adults with early onset (£40yrs) T2D. The study will longitudinally follow this cohort (total N=2250) of 9-13 year old girls and 10- 14 year old boys (site n=150) with BMI ≥ 85%ile and PreDM, as defined by HbA1c, fasting glucose, and/or 2-hr glucose on oral glucose tolerance test (OGTT), over 3 years or diagnosis of T2D, whichever occurs first. They will collect anthropometric, cardiovascular, behavioral, and genetic risk factors, as well as SDoH measures. Physiologic testing, including mathematical modelling of insulin kinetics and free fatty acid flux (FFA) using a 3- hour OGTT, in vivo continuous glucose monitoring (CGM), and body composition, will be collected. Aims: 1) To develop reliable estimates of YoT2D risk in youth with PreDM, overall and according to risk factor profiles that differentiate groups based on their risk of progression to YoT2D, 2) To characterize the early pathophysiologic drivers of YoT2D. a. To study differences in insulin kinetics (secretion, sensitivity, clearance), FFA flux, CGM, ectopic fat (visceral, hepatic), and cardiovascular risk between youth who progress to YoT2D and those who do not. b. To determine whether these pathophysiologic differences differ by risk factor groups identified in Aim 1. This proposal employs a multidisciplinary team with a novel mix of expertise in SDoH, stakeholder engagement, and metabolic pathophysiology, an innovative recruitment approach, and cutting-edge, novel methodologies to investigate the risk factors and pathophysiologic drivers that predict and cause YoT2D, in order to inform future prevention and treatment strategies.

项目总结/文摘