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.

项目概要 肥胖和随后的 2 型糖尿病 (T2D) 在青少年中越来越常见，但肥胖的表型 我们帮助领导的 NIDDK TODAY 研究表明，青少年发病的 T2D (YO-T2D) 与成人不同。 患有 T2D 的青少年口服药物失败率高（约 50%）且快速，并且更快需要胰岛素治疗 与在 ADOPT 研究中接受相似持续时间治疗的成人相比，在我们的 NIDDK RISE 研究中，进一步证明了这一点： 糖耐量受损 (IGT) 或新诊断的 T2D 青少年的治疗反应 直接与体重指数和初始血糖相似的成年人进行比较，青少年的胰岛素抵抗程度是成年人的两倍 与给予相同剂量的成人相比，β细胞功能和血糖控制迅速恶化 最后，在我们的 HIP 研究中，二甲双胍并没有改善胰岛素水平。 即使在肥胖的血糖正常的青少年中，即使在青春期早期就开始敏感或分泌，争论 最令人担忧的是，《今日》证实了微血管糖尿病的发病率。 并发症的发生率从 32% 到 68% 不等，平均年龄仅为 26.4±2.8 岁，影响应在 他们的生产力高峰期；并发症对少数族裔/族裔的影响更大，提高了 这种前所未有的早期发病率和预计的医疗保健费用令人担忧。 重点定义 a) 青少年理想的 T2D 诊断和/或筛查标准 b) 病理生理学要求 Y-T2D 和成人发病的 T2D 之间的区别 c) 如何预防 Y-T2D d) 如何更好地治疗 Y-T2D 一次 尽管发展 Y-T2D 的一些危险因素（例如家族史、肥胖等）已明确， 这些高危青少年中只有一小部分在青少年时期发展为 T2D。因此，其他因素也是有原因的。 需要探索，例如不良的童年经历、压力、贫困、种族主义、睡眠/昼夜节律、 我们建议久坐行为之间的细微差异以及青春期激素的确切影响。 招募并纵向追踪 3,540 名来自城市、有罹患 T2D 风险的不同青年（我们网站中的 236 名） 以及处于青春期早期的农村地区，每 6 个月进行一次纵向评估（HbA1c、 每 6 个月进行一次 Taneda 量表，每年一次 OGTT/DXA/MRI），并配有额外的样品存储以供分析一次 积累了新发 T2D 青少年的“临界量”，我们提出以下具体目标： 与来自人口不成比例的利益相关者/社区成员合作开发 受 T2D 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、青春期激素以及库 血液、粪便、头发和尿液 2. 为了评估社会心理和心理因素，我们将测量压力、 歧视、戏弄、微侵犯、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公正的数据分析方法来识别生物标志物 评估进展风险，并为谁将患上 Y-T2D 建立一个预测模型。