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.

摘要 而肥胖、血统、糖尿病家族史、胰岛素抵抗和青春期都是危险因素。 儿童首发2型糖尿病(T2D)的因素，确定青少年患糖尿病风险最高的亚群 从“前驱糖尿病”进展到T2D和恶化的机制仍然存在 难以捉摸。这种缺乏针对性的做法违背了医学界直接照顾青少年的能力 在儿童发病风险最大的T2D和2)制定有针对性的干预措施。特别的是 儿童T2D的攻击性和青少年独特的激素环境提示 虽然成人发病T2D的机制在儿科T2D中有共鸣，但其他 微扰是有效的。我们的团队建议合作进行一项多中心研究，知情的 通过与家庭和社区成员的伙伴关系，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 对青春期的胰岛素抵抗的影响。我们建议进行一项纵向研究，利用3个小时， 在基线、18个月和36个月时进行多样本口服葡萄糖耐量试验 患有糖尿病前期的肥胖青春期青年1)测试1小时血糖在预测中的有效性 T2D和胰岛素分泌恶化，2)进行广泛的表型检测 胰岛素分泌变化(早期和第二时相)与胰岛素敏感性、 胰岛素分泌、胰升糖素抑制、肝脏葡萄糖清除和游离脂肪流量 T2D的出现。遗传变异在子宫环境、内脏脂肪中的作用 积累，饮食行为，精神健康问题，健康的社会决定因素，饮食，身体 活动、睡眠和冠状病毒感染对胰岛素分泌和敏感性的扰动将是 测试过。家庭保健工作者将提供对家庭环境的更多重要见解。 葡萄糖增强的精氨酸刺激测试将在以下几个参与者中进行 谁的血糖稳态被保存，恶化，或进展到T2D。这项研究是预期的 指定T2D风险的有用指标并加深我们对以下基础的理解 胰岛素分泌和敏感性的进行性缺陷为个体化计划提供信息 干扰了T2D的出现。