Identify risk factors for type 2 diabetes in adolescents

确定青少年 2 型糖尿病的危险因素

• 批准号: 10584207
• 负责人: Ihuoma U Eneli
• 金额: $ 5.8万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-19 至 2029-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584207
• 关键词: Address; Adolescent; Adolescent Development; Adolescent obesity; Adult; Age; American; Area; B-Lymphocytes; Behavior; Beta Cell; Blood specimen; Body mass index; C-Peptide; C-reactive protein; Carbohydrates; Caring; Cell physiology; Cells; Child; Childhood; Clinical; Complement; Complement Factor H; Continuous Glucose Monitor; Copy Number Polymorphism; County; Demographic Factors; Deterioration; Development; Diabetes Mellitus; Diagnosis; Diagnostic Sensitivity; Diagnostic Specificity; Diagnostic tests; Discrimination; Disease; Early Diagnosis; Early identification; Edetic Acid; Enzymes; Erythrocytes; Ethnic Origin; Exposure to; Family; Feces; Functional disorder; Future; Gene Dosage; Genetic; Genomic DNA; Glucose; Glucose tolerance test; Glycosylated hemoglobin A; Immune Response Genes; Impaired fasting glycaemia; Incidence; Inflammation; Inflammatory; Innate Immune Response; Insulin; Insulin Resistance; Intervention Studies; Intravenous; Islet Cell; Leukocytes; Life Style; Literature; Mental Health; Metabolic; Metabolic dysfunction; Morbidity - disease rate; Multi-site clinical study; Natural Immunity; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Ohio; Oral; Pattern; Phenotype; Physical activity; Plasma; Play; Poverty; Process; Prospective, cohort study; Proteins; Protocols documentation; Psychosocial Factor; Race; Recommendation; Recording of previous events; Research; Risk; Risk Factors; Role; Rural; Saliva; Sampling; Social Impacts; Standardization; Stress; Variant; Weight; Weight Gain; Youth; adverse childhood events; aged; body system; clinical center; clinical research site; cohort; deprivation; design; diabetic; epidemiology study; experience; glycemic control; high risk; impaired glucose tolerance; indexing; inflammatory marker; insulin secretion; insulin sensitivity; intravenous glucose tolerance test; microbiome; neighborhood disadvantage; nutrition; peripheral blood; prevent; prospective; psychologic; psychosocial; recruit; response; rural setting; screening; sex; social health determinants; socioeconomics; stool sample; urban setting; waist circumference

Type 2 diabetes (T2D), a condition marked by substantial physical and psychological morbidity, is increasingly diagnosed in youth but is still infrequent even in high-risk obese adolescents. There are significant racial, ethnic, and socioeconomic effects in youth at risk for the development of T2D, but we do not know how to easily identify which youth will and will not develop T2D, nor do we know specifics about the mechanisms behind the early development of T2D. To address these research gaps amongst others, we propose an appropriately powered prospective cohort study of 3500 youth in response to RFA DK-21-002 Understanding and Targeting the Pathophysiology of Youth-Onset Type 2 Diabetes-Clinical Centers. As the Columbus Clinical Center (CCC), our interdisciplinary team will leverage our large clinical network in urban and rural settings in Ohio AND cumulative experience and expertise caring for youth with obesity and type 2 diabetes, recruiting and retention in prospective clinical/cohort trials and diagnostic testing for diabetes. In addition, we propose mechanistic studies drawing from our prior studies on insulin sensitivity and secretion, β-cell function, innate immune response genes, inflammatory markers, and microbiome. As the CCC, we plan to recruit and retain a cohort of 250 youth aged 9-13 years with obesity (age and sex-specific body mass index (BMI) ≥ 95%tile) with impaired fasting glucose (IFG) (100-125mg/dl) or impaired glucose tolerance (IGT) (140–199mg/dl) in urban and rural Ohio counties over 30 months and propose. Subjects will be followed to determine the pattern and trajectory of anthropometric change (weight, BMI, Tanner stage) as risk factors for T2D, and to investigate a risk phenotype for youth for T2D based on a) social determinants of health, b) lifestyle behaviors and c) psychosocial factors. Oral glucose tolerance tests will be performed every 6 months to diagnosis diabetes and also to assess insulin sensitivity and secretion changes that identify early risk for development of T2D. Continuous glucose monitoring (CGM) and hemoglobin A1c levels will also be assessed throughout the study to identify early markers for development of T2D. Lastly, blood and stool samples will be collected and saved for future assessment of genetic, inflammatory and microbiome factors that play a mechanistic role in the development of T2D. The results of this study will have broad clinical and social impact by identifying youth specifically at risk for T2D and by identifying specific psychosocial risk factors for adolescent T2D. They will have research impact by identifying mechanistic factors for the development of adolescent T2D that may be targeted in future interventional studies to prevent the disease.

2型糖尿病（T2 D）是一种以大量身体和心理发病率为特征的病症， 在青少年中诊断，但即使在高危肥胖青少年中也不常见。有显著的种族， 种族和社会经济影响的青年在风险的发展T2 D，但我们不知道如何 我们很容易确定哪些年轻人会和不会发展为T2 D，我们也不知道有关机制的具体情况， T2 D早期发展的背后。为了解决这些研究差距，我们提出了一个 对RFA DK-21-002的3500名青年进行的适当把握度前瞻性队列研究 针对青年发病2型糖尿病的病理生理学-临床中心。作为哥伦布临床 中心（CCC），我们的跨学科团队将利用我们在城市和农村环境中的大型临床网络， 俄亥俄州和积累的经验和专业知识照顾青少年肥胖和2型糖尿病，招聘 并保留在前瞻性临床/队列试验和糖尿病诊断测试中。此外，我们建议 从我们先前对胰岛素敏感性和分泌、β细胞功能、先天性胰岛素抵抗和胰岛素抵抗的研究中得出的机制研究 免疫反应基因、炎症标志物和微生物组。作为CCC，我们计划招募和保留一名 250名9-13岁的肥胖青少年（年龄和性别特异性体重指数（BMI）≥ 95%）队列， 空腹血糖受损（IFG）（100- 125 mg/dl）或糖耐量受损（IGT）（140- 199 mg/dl） 和俄亥俄州的乡村县超过30个月，并提出。将对受试者进行随访，以确定模式， 人体测量学变化轨迹（体重、BMI、坦纳分期）作为T2 D的风险因素，并研究 基于a）健康的社会决定因素，B）生活方式行为和c） 心理社会因素口服葡萄糖耐量试验将每6个月进行一次，以诊断糖尿病， 还评估胰岛素敏感性和分泌变化，以确定T2 D发展的早期风险。 还将在整个研究期间评估动态血糖监测（CGM）和血红蛋白A1 c水平 以确定T2 D发展的早期标志物。最后，将收集并保存血液和粪便样本 用于未来评估在这些疾病中发挥机械作用的遗传、炎症和微生物组因素， T2 D的发展。这项研究的结果将有广泛的临床和社会影响， 特别是T2 D的风险，并确定青少年T2 D的特定心理社会风险因素。他们将 通过确定可能导致青少年T2 D发展的机制因素， 未来干预研究的目标是预防该疾病。