Understanding the Pathophysiology of Type 2 Diabetes in Navajo Youth

了解纳瓦霍青年 2 型糖尿病的病理生理学

• 批准号: 10583405
• 负责人: Dana Dabelea
• 金额: $ 5.48万
• 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: 2023-03-01 至 2029-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583405
• 关键词: Adult; Affect; Age; American Indians; Area Under Curve; Behavior; Behavioral; Beta Cell; Biological; Biological Markers; Biometry; Body mass index; Cell physiology; Characteristics; Clinical; Collaborations; Collection; Colorado; Communities; Data; Development; Diabetes Mellitus; Diabetes autoantibodies; Disease; Disease Progression; Enrollment; Ethnic Origin; Etiology; Exposure to; Family history of; Functional disorder; Genetic; Glucose; Goals; Homeostasis; Hour; Individual; Insulin; Investments; Knowledge; Leadership; Life; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Navajo; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Obesity Epidemic; Overweight; Participant; Pathway interactions; Pattern; Phenotype; Physiological; Prevention; Prevention approach; Productivity; Protocols documentation; Psychosocial Factor; Psychosocial Stress; Puberty; Public Health; Race; Research; Risk; Risk Assessment; Risk Factors; Risk Management; Rural Community; Subgroup; Universities; Visit; Work; Youth; case control; clinical research site; cohort; critical period; design; diabetes risk; diagnostic accuracy; emerging adult; ethnic minority population; experience; high risk; insulin sensitivity; maternal diabetes; obesity in children; participant retention; pre-clinical; predictive modeling; prevent; psychosocial; racial minority population; recruit; risk prediction; rural residence; sex; social factors; social health determinants; trend

PROJECT ABSTRACT Type 2 diabetes (T2D) is on the rise among youth in the US and worldwide, and disproportionately affects racial and ethnic minority populations including American Indians. The number of at-risk youth continues to increase alongside the child obesity epidemic, with an unprecedented proportion of youth developing T2D during puberty. The public health implications of this trend are highly significant, as debilitating complications are likely to manifest by early adulthood during what should be the most active and productive years of life. Prevention of youth-onset T2D is crucial as the course of disease is more aggressive than the typical “adult-onset T2D”. Yet current knowledge of the pathophysiology of youth-onset T2D is limited, so it is still unclear whom to target or how to prevent youth-onset T2D. Puberty is a critical period for T2D development, as this life stage is characterized by marked changes in insulin sensitivity that do not always resolve by the end of puberty. Prior studies largely used cross-sectional or case-control designs, or longitudinal protocols that rarely spanned the duration of puberty, precluding a holistic synthesis of how longitudinal patterns of change in biomarkers of glucose-insulin homeostasis culminate in youth-onset T2D. Deciphering the pathways leading to youth-onset T2D is fundamental to understanding pre-clinical disease progression, which has potential to directly inform targeted prevention approaches. With RFA-DK-21-002, the NIDDK seeks to establish a cohort of early pubertal youth at risk for T2D to better understand the pathophysiology of youth-onset T2D. We propose here a Colorado|Navajo clinical site that will recruit for this consortium 400 rural-dwelling American Indian youth, the subgroup at highest risk for youth-onset T2D. Under leadership from the University of Colorado, this clinical site will be based in a rural community on the Navajo Nation where we have conducted youth diabetes research since 2000. We will enroll youth in early puberty (Tanner Stages 2-3) who have elevated risk for youth-onset T2D based on overweight or obesity status (BMI ≥85th percentile) and self-identification with American Indian race. Participants will be followed for 33 months, on average, undergoing annual 2-hour oral glucose tolerance tests (n= 3-4 per participant) and semi-annual visits (n= 3-4 per participant) for collection of additional biospecimens and data on physiological, behavioral, familial, and psychosocial factors associated with T2D risk. Our specific aims are: 1) locally, recruit 400 American Indian youth in the early stages of puberty (Tanner stage 2-3) with overweight or obesity, and follow them longitudinally to assess the risk of T2D; 2) across the consortium, identify patterns of change in biomarkers of glucose-insulin homeostasis that culminate in development of youth- onset T2D; and 3) across the consortium, develop prediction models for youth-onset T2D and identify sub- phenotypes of incident youth-onset T2D.

项目摘要 2 型糖尿病 (T2D) 在美国和世界各地的年轻人中呈上升趋势，并且对种族的影响尤为严重 以及包括美洲印第安人在内的少数族裔人口 处于危险中的青少年人数持续增加。 除了儿童肥胖流行之外，青春期患 T2D 的青少年比例也达到了前所未有的水平。 这一趋势对公共卫生的影响非常重大，因为令人衰弱的并发症可能会导致 表现在成年早期，这应该是生命中最活跃和最富有成效的时期。 青年发病的 T2D 至关重要，因为其病程比典型的“成人发病的 T2D”更具侵袭性。 目前对青年发病的 T2D 病理生理学的了解有限，因此仍不清楚针对谁或 如何预防青少年发病的 T2D 青春期是 T2D 发展的关键时期，因为这个阶段是 T2D 发展的关键时期。 其特点是胰岛素敏感性发生显着变化，但这种变化在青春期结束时并不总能解决。 研究主要使用横断面或病例对照设计，或很少跨越整个研究范围的纵向方案。 青春期的持续时间，排除了生物标志物纵向变化模式的整体综合 葡萄糖-胰岛素稳态最终导致青少年发病的 T2D。 T2D 是了解临床前疾病进展的基础，它有可能直接告知 NIDDK 试图通过 RFA-DK-21-002 建立一组青春期早期的预防方法。 为了更好地了解青年发病的 T2D 的病理生理学，我们提出了以下建议： 科罗拉多|纳瓦霍临床站点将为该联盟招募 400 名居住在农村的美国印第安青年， 在科罗拉多大学的领导下，该临床中心是青少年发病 T2D 风险最高的亚组。 将设在纳瓦霍族部落的一个农村社区，我们在那里进行了青少年糖尿病研究 自 2000 年以来。我们将招募处于青春期早期（Tanner 阶段 2-3）的青少年，他们的青少年发病风险较高 基于超重或肥胖状况（BMI ≥85%）和美洲印第安人自我认同的 T2D 参与者将被跟踪平均 33 个月，每年接受 2 小时的口服葡萄糖耐量测试。 测试（n = 每位参与者 3-4 次）和半年访视（n = 每位参与者 3-4 次）以额外收集 与 T2D 风险相关的生理、行为、家庭和社会心理因素的生物样本和数据。 我们的具体目标是：1）在当地招募400名处于青春期早期（坦纳阶段）的美国印第安青年 2-3) 超重或肥胖，并纵向跟踪他们以评估整个联盟的 T2D 风险； 确定葡萄糖-胰岛素稳态生物标志物的变化模式，最终导致青少年的发育 3) 在整个联盟中，开发青少年发病的 T2D 预测模型并确定亚型 青年发病的 T2D 的表型。