What Activates Type 2 diabetes in Children (WATCH)

是什么引发了儿童 2 型糖尿病（观看）

• 批准号: 10582468
• 负责人: MEGAN MORIARTY KELSEY
• 金额: $ 5.02万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-10 至 2029-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582468
• 关键词: Acute; Address; Adolescent; Adult; Affect; Age; Amputation; Anxiety; Attention; Behavior; Behavior monitoring; Beta Cell; Biolectric Impedance; Biological; Blood Banks; Body Composition; Body mass index; COVID-19; Cardiovascular system; Cell physiology; Child; Chronic; Circadian Rhythms; Code; Collaborations; Communities; Complications of Diabetes Mellitus; Creativeness; Data; Data Analyses; Deterioration; Development; Diabetes Mellitus; Diabetes prevention; Diabetic Angiopathies; Diagnostic; Discrimination; Disease; Dual-Energy X-Ray Absorptiometry; Ecological momentary assessment; Education; Enrollment; Ethnic Origin; Event; Exposure to; Failure; Family; Feces; Future; Genetic; Gestational Diabetes; Glycosylated hemoglobin A; Goals; Hair; Health Care Costs; Health Services Accessibility; Hormones; Hydrocortisone; In Situ; Incidence; Income; Individual; Insulin; Insulin Resistance; Intervention; Intervention Studies; Interview; Lead; Lipids; Machine Learning; Magnetic Resonance Imaging; Measures; Mental Depression; Mental Health; Metabolic; Metformin; Methodology; Monitor; Morbidity - disease rate; Myocardial Infarction; National Institute of Diabetes and Digestive and Kidney Diseases; Newly Diagnosed; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Oral; Outcome; Participant; Pattern; Perception; Pharmaceutical Preparations; Phenotype; Physical activity; Physiological; Pilot Projects; Polysomnography; Population; Poverty; Prevention approach; Prevention strategy; Productivity; Psychological Factors; Psychosocial Assessment and Care; Psychosocial Factor; Puberty; Questionnaires; Race; Recording of previous events; Risk; Risk Factors; Role; Rural Community; Sampling; Schedule; Site; Sleep; Sleep disturbances; Social status; Standardization; Stress; Stroke; Time; Urban Community; Urine; Visit; Weight Gain; Youth; adverse childhood events; biomarker identification; bullying; cardiometabolism; comorbidity; comparison control; design; early onset; follow-up; glycemic control; health disparity; health equity promotion; high risk; impaired glucose tolerance; innovation; insulin secretion; insulin sensitivity; medication compliance; member; microaggression; novel; optimal treatments; pandemic disease; predictive modeling; prevent; progression risk; psychosocial; racial minority; racism; recruit; response; rural area; screening; sedentary lifestyle; social; treatment response; type 2 diabetes in children; urban area

PROJECT SUMMARY Obesity and subsequently type 2 diabetes (T2D) is increasingly common in adolescents, but the phenotype of youth-onset T2D (YO-T2D) differs from adults. The NIDDK TODAY study we helped lead, demonstrated that youth with T2D had a high (≈50%) and rapid failure rate on oral medications and faster need for insulin therapy vs. adults treated for a similar duration in the ADOPT study. As further evidence, in our NIDDK RISE study, where treatment responses in youth with impaired glucose tolerance (IGT) or newly diagnosed T2D were directly compared to adults of similar BMI and initial glycemia, youth were twice as insulin resistant as adults and had rapid deterioration of β-cell function and glycemic control compared to adults given the same treatment with similar medication adherence. Finally in our HIP study, metformin did not improve insulin sensitivity or secretion even when started early in puberty in normoglycemic youth with obesity, arguing for innovative approaches. Of most concern, TODAY demonstrated an incidence of microvascular diabetes complications ranging from 32-68% by a mean age of only 26.4±2.8 yrs, affecting individuals who should be at their peak of productivity; complications more heavily affected those with minority race/ethnicity, raising concerns related to health disparities. This unprecedented early morbidity and projected health care costs mandate a focus on defining a) the ideal T2D diagnostic and/or screening criteria for youth b) pathophysiologic distinctions between Y-T2D and adult-onset T2D c) how to prevent Y-T2D d) how to better treat Y-T2D once present. Though some risk factors for developing Y-T2D (e.g. family history, obesity, etc.) are well-established, only a small subset of these high-risk youth progress to T2D as adolescents. Thus, other causal components need to be explored, such as adverse childhood experiences, stress, poverty, racism, sleep/circadian rhythm, subtle differences within sedentary behavior, and the exact impact(s) of pubertal hormones. We propose to enroll and follow longitudinally 3,540 diverse youth (236 from our site) at risk for developing T2D from urban and rural locations who are early in puberty, and perform longitudinal assessments every 6 mo (HbA1c, Taneda scale every 6 mo, OGTT/DXA/MRI, yearly) paired with additional sample storage to be analyzed once a “critical mass” of youth with new-onset T2D is accumulated. We propose the following Specific Aims, developed in collaboration with our stakeholders/community members from populations disproportionately affected by T2D: 1. To assess patterns of change in metabolic and pubertal events, we will measure: glycemia, insulin sensitivity/secretion, body composition, free living behaviors, and pubertal hormones, as well as bank blood, stool, hair, and urine. 2. To assess psychosocial and psychological factors, we will measure stress, discrimination, teasing, microaggressions, social status, access to care, depression/anxiety, and cortisol. 3. To use the data collected in Aims 1 and 2 and apply unbiased data analysis methodology to identify biomarkers for progression risk and develop a prediction model for who will develop Y-T2D.

项目摘要 肥胖和随后的2型糖尿病（T2D）在青少年中越来越普遍，但是 青年发作的T2D（YO-T2D）与成年人不同。我们帮助领导的NIDDK今天的研究表明 T2D的青年对口服药物的较高（约50％）和快速衰竭率，胰岛素治疗的需求更快 在采用研究中，与成年人进行了类似持续时间的治疗。作为进一步的证据，在我们的NIDDK崛起研究中， 葡萄糖耐量受损（IGT）或新诊断为T2D的青年的治疗反应是 与类似BMI和初始糖脂的成年人直接相比，青少年的胰岛素耐药性是成年人的两倍 与成年人相比 具有类似药物依从性的治疗。最后，在我们的髋关节研究中，二甲双胍没有改善胰岛素 即使在肥胖症的正常血糖青年开始青春期的早期开始，敏感或分泌 创新的方法。最关心的是，今天证明了微血管糖尿病的事件 并发症的平均年龄为32-68％，只有26.4±2.8岁，影响应在 他们的生产力高峰；并发症更严重地影响了少数族裔/种族的人，并提高 与健康分布有关的问题。这种前所未有的早期发病率和预计医疗保健费用 授权专注于定义a）理想的T2D诊断和/或筛查标准b）病理生理学 Y-T2D和成人发作的T2D c）如何预防Y-T2D d）如何更好地治疗Y-T2D 展示。尽管一些开发Y-T2D的风险因素（例如家族史，肥胖等）是完善的，但 这些高风险的青年中只有一小部分作为青少年发展到T2D。那，其他因果成分 需要探索，例如不利的童年经历，压力，贫穷，种族主义，睡眠/昼夜节律， 久坐行为的细微差异以及青春期激素的确切影响。我们建议 注册并关注3,540名潜水员青年（来自我们网站的236名）有可能从Urban开发T2D的风险 和青春期早期的粗糙地点，每6个月进行纵向评估（HBA1C， 每年6个月taneda量表每年一次，每年一次）与待分析的其他样品存储配对 积累了新发行T2D的年轻人的“临界质量”。我们提出以下特定目标， 与我们的利益相关者/社区成员合作开发的人口不成比例 受T2D的影响：1。为了评估代谢和青春期事件的变化模式，我们将测量：血糖， 胰岛素敏感性/分泌，身体成分，自由生活行为和青春期激素以及银行 血，凳子，头发和尿液。 2。为了评估社会心理和心理因素，我们将衡量压力， 歧视，戏弄，微攻击，社会地位，获得护理，抑郁/焦虑和皮质醇。 3 使用目标1和2中收集的数据，并应用无偏的数据分析方法来识别生物标志物 为了进步风险并为谁开发Y-T2D开发预测模型。