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(T2D)是一种以严重的身体和心理疾病为标志的疾病，其发病率越来越高 在年轻时被诊断出来，但即使在高危肥胖青少年中也很少见。有重大的种族问题， T2D发展对处于危险中的青年的种族和社会经济影响，但我们不知道如何 很容易确定哪些年轻人会和哪些不会发展成T2D，我们也不知道具体的机制 T2D早期开发的背后。为了解决这些研究差距，我们提出了一种 3500名青年对RFA DK-21-002理解的适当支持的前瞻性队列研究 和针对青年起病的2型糖尿病的病理生理学-临床中心。作为哥伦布诊所 中心(CCC)，我们的跨学科团队将利用我们在城乡环境中的大型临床网络 俄亥俄州和累积的肥胖症和2型糖尿病青少年护理经验和专业知识，招聘 以及糖尿病的前瞻性临床/队列试验和诊断测试中的保留率。此外，我们建议 机制研究源于我们先前关于胰岛素敏感性和分泌、β细胞功能、先天的研究 免疫反应基因、炎症标志物和微生物组。作为中央协调中心，我们计划招聘和保留一名 250名9-13岁的肥胖青年(年龄和性别特定的体重指数≥为95%) 城市空腹血糖受损(100-125 mg/dl)或糖耐量受损(140-199 mg/dl) 和俄亥俄州农村县超过30个月，并提出建议。受试者将被跟踪以确定模式和 作为T2D危险因素的人体测量变化轨迹(体重、BMI、Tanner分期)，并调查 青少年T2D的风险表型基于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。将每6个月进行一次口服葡萄糖耐量试验，以诊断糖尿病和 此外，评估胰岛素敏感性和分泌变化，以确定T2D发生的早期风险。 连续血糖监测(CGM)和血红蛋白A1c水平也将在整个研究过程中进行评估 寻找T2D发生的早期标志物。最后，采集血液和粪便样本并保存 用于未来对遗传、炎症和微生物组因素的评估，这些因素在 T2D的发展。这项研究的结果将通过识别年轻人产生广泛的临床和社会影响 特别是T2D的风险，并确定青少年T2D的特定心理社会风险因素。他们会 通过确定青少年T2D发展的机制因素来产生研究影响 在未来的干预研究中有针对性地预防这种疾病。