Assessing Diabetes Risk Origins in Teens (ADROIT)

评估青少年糖尿病风险起源 (ADROIT)

• 批准号: 10583938
• 负责人: LORRAINE E LEVITT KATZ
• 金额: $ 8.52万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-05 至 2029-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583938
• 关键词: Acceleration; Adipose tissue; Adolescence; Adolescent; Adult; Algorithms; Arginine; Beta Cell; Biological Markers; Body Composition; Caring; Child; Childhood; Childhood diabetes; Clinical; Collaborations; Communication; Communities; Community Health Aides; Community Healthcare; DNA; Data; Data Collection; Defect; Deterioration; Development; Diabetes Mellitus; Diet; Disease; Eating Behavior; Eating Disorders; Education; Environment; Evaluation; Exposure to; Family; Family history of; Fatty acid glycerol esters; Fetal Growth Retardation; Fetal Macrosomia; Future; Genetic Risk; Genomics; Genotype; Glucagon; Glucose; Goals; Growth; Health Personnel; Hepatic; Home Care Services; Home environment; Hormonal; Hour; Human; Infection; Institution; Insulin; Insulin Resistance; Interruption; Intervention; Life Style; Longitudinal Studies; Longitudinal cohort; Medical; Medical Care Team; Mental Health; Metabolic; Methodology; Methods; Mission; Molecular; Multicenter Studies; Nature; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Participant; Patients; Pediatric Hospitals; Phase; Phenotype; Philadelphia; Physical activity; Physical assessment; Plasma; Population; Prediabetes syndrome; Prevalence; Process; Prospective Studies; Protocols documentation; Psychosocial Factor; Puberty; RNA; Reporting; Research; Research Design; Resources; Risk; Risk Factors; Sampling; Science; Secretory Cell; Secretory Rate; Sleep; Specific qualifier value; Specificity; Standardization; Teenagers; Testing; Viral; Visceral; Youth; actigraphy; adipokines; anxiety symptoms; base; biobank; blood glucose regulation; clinical center; community based participatory research; coronavirus disease; depressive symptoms; design; diabetes risk; digital health; genetic variant; healthy weight; high risk; in utero; indexing; innovation; insight; insulin secretion; insulin sensitivity; intrauterine environment; maternal diabetes; member; open source; phenomics; physical inactivity; prenatal exposure; preservation; prevent; programs; recruit; screening; sleep health; social health determinants; study population; tool

ABSTRACT While obesity, ancestry, family history of diabetes, insulin resistance, and puberty are all risk factors for pediatric-onset type 2 diabetes (T2D), identifying the subset of youth at greatest risk of advancing from “prediabetes” to T2D and the mechanisms underlying the deterioration remain elusive. This lack of specificity defies the medical community's ability to 1) direct care to the youth at greatest risk of pediatric onset T2D and 2) develop targeted interventions. The particularly aggressive nature of pediatric T2D and the unique hormonal milieu of the adolescent suggest while the mechanisms underlying adult-onset T2D in adults resonate in pediatric T2D, additional perturbances are operative. Our team proposes to collaborate in a multi-center study, informed by partnerships with family and community members, to define clinically accessible metrics of increased diabetes risk as well as potential mechanisms that compromise the normal adaptations to insulin resistance during adolescence. We propose a longitudinal study leveraging a 3-hour, multi-sample oral glucose tolerance test performed at baseline, 18-months, and 36-months in obese pubertal youth with pre-diabetes to 1) test the utility of the one-hour glucose in predicting T2D and deterioration in insulin secretion, 2) perform extensive phenotyping for testing the relationships of changes in insulin secretion (early phase and second phase), insulin sensitivity, incretin secretion, glucagon suppression, hepatic glucose clearance, and free fatty flux with emergence of T2D. The contributions of genetic variants, in utero environment, visceral adipose accumulation, eating behaviors, mental health issues, social determinants of health, diet, physical activity, sleep and COVID infection to perturbances in insulin secretion and sensitivity will be tested. Home health care workers will provide additional critical insight into the home environment. Glucose-potentiated arginine stimulation tests will be conducted in subsets of participants in whom glucose homeostasis is preserved, worsens, or advances to T2D. This study is anticipated to specify useful indicators of T2D risk and advance our understanding of the underpinnings of progressive defects in insulin secretion and sensitivity to inform individualized programs aimed at interrupting emergence of T2D.

抽象的 肥胖、血统、糖尿病家族史、胰岛素抵抗和青春期都是风险 儿科发病 2 型糖尿病 (T2D) 的影响因素，确定最有风险的青少年群体 从“糖尿病前期”发展为 T2D，且恶化的机制仍然存在 难以捉摸。这种缺乏特异性违背了医学界 1) 直接护理青少年的能力 2) 制定有针对性的干预措施。特别是 儿科 T2D 的攻击性本质和青少年独特的激素环境表明 虽然成人发病的 T2D 的潜在机制在儿童 T2D 中也有共鸣，但 扰动正在发挥作用。我们的团队建议合作进行一项多中心研究， 通过与家庭和社区成员的合作，定义临床上可访问的指标 糖尿病风险增加以及损害正常适应的潜在机制 青春期的胰岛素抵抗。我们建议进行一项为期 3 小时的纵向研究， 在基线、18 个月和 36 个月进行的多样本口服葡萄糖耐量测试 患有糖尿病前期的肥胖青春期青少年 1) 测试一小时血糖在预测中的效用 T2D 和胰岛素分泌恶化，2) 进行广泛的表型分析以测试 胰岛素分泌变化（早期和第二阶段）、胰岛素敏感性、 肠促胰岛素分泌、胰高血糖素抑制、肝葡萄糖清除率和游离脂肪通量 T2D 的出现。遗传变异对子宫环境、内脏脂肪的贡献 积累、饮食行为、心理健康问题、健康的社会决定因素、饮食、身体 活动、睡眠和新冠病毒感染对胰岛素分泌和敏感性的干扰将 已测试。家庭保健工作者将对家庭环境提供额外的重要见解。 将对部分参与者进行葡萄糖强化精氨酸刺激试验 葡萄糖稳态保持不变、恶化或进展为 T2D。这项研究预计 指定 T2D 风险的有用指标并加深我们对 T2D 风险基础的理解 胰岛素分泌和敏感性的进行性缺陷可为针对的个体化计划提供信息 中断 T2D 的出现。