Early life stress and cardiometabolic health in adolescence

青春期早期生活压力和心脏代谢健康

• 批准号: 10192816
• 负责人: Megan R Gunnar
• 金额: $ 75.82万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192816
• 关键词: Address; Adolescence; Adolescent; Adopted; Adoption; Adult; Age; Aging; American Heart Association; Animal Model; Area; Atherosclerosis; Birth; Body mass index; Cardiac health; Cardiometabolic Disease; Cardiovascular Diseases; Caring; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Cholesterol; Clinical; Data; Development; Disease; Early Intervention; Education; Excision; Exhibits; Exposure to; Family; Fatty acid glycerol esters; Food; Future; Goals; Health; Health behavior; Heart Diseases; Home; Hypertension; Immune; Impairment; Income; Infant; Insulin; International; Intervention; Knowledge; Life; Link; Lipids; Literature; Longevity; Measures; Mediating; Mediator of activation protein; Metabolic; Metabolic Diseases; Mission; Modeling; Motion; Neurobiology; Orphanages; Outcome; Parents; Pathway interactions; Physiology; Plant Roots; Population; Process; Prospective Studies; Provider; Public Health; Recording of previous events; Regulation; Reporting; Research; Resources; Role; Sex Differences; Shapes; Signal Transduction; Specific qualifier value; Stress; System; T-Lymphocyte; Testing; United States National Institutes of Health; Work; Youth; adopted child; arterial stiffness; base; cardiometabolic risk; cardiometabolism; cardiovascular health; cardiovascular risk factor; deprivation; disability; disorder risk; early experience; early life stress; experience; fasting glucose; improved; indexing; infancy; male; novel; nutrition; pathogen exposure; prevent; preventable death; programs; prospective; resilience; senescence

Abstract Poor cardiometabolic health, encompassing both cardiovascular and metabolic diseases, is the leading cause of preventable death worldwide. There is growing evidence that childhood exposure to stress increases lifespan cardiometabolic risk. The proposed study addresses 4 gaps in the literature recently identified by the American Heart Association: (1) the need for prospective studies, (2) the need to better specify periods of greater vulnerability to stress with regards to cardiometabolic health, (3) the need for more evidence on mechanistic pathways, and (4) the need for more studies that explore sex differences. Our central hypothesis that infancy is a important period for setting in motion processes that increase cardiometabolic disease risk. Our model of early life stress (ELS) will be orphanage-rearing experienced by children adopted internationally. We will assess cardiometabolic functioning in adolescence, the earliest age period when these assessments are associated with adult cardiovascular health. We will compare adolescents adopted as infants or very young children from orphanages into well-resourced homes with youth reared in their natal families of comparable educations and incomes. We will address three specific aims: 1) Determine the relationship between significant ELS in the first few years of life and cardiometabolic functioning in adolescence, 2) determine factors that mediate or partially mediate the association of ELS with cardiometabolic function and changes in functioning during adolescence, and 3) explore the sex differences in ELS- cardiometabolic risk associations. Under the first aim, arterial stiffness and fasting glucose, insulin, and lipids levels will be examined. For the second aim, the impact of ELS on cardiometabolic functioning in adolescence will be examined with the mediators of altered stress system activity, indices of immune aging, increased trunk fat mass and poorer health behaviors. In the third aim, sex differences will be examined in the outcomes in aim 1 and associations with potential mediators in aim 2. These aims are based on significant preliminary data. The impact of this study will be (1) improved understanding of the importance of the first few years of life for cardiometabolic health, (2) a deeper characterization of the mechanisms and pathways through which ELS-cardiometabolic risk is instantiated and (3) determination of whether there are sex differences in either the association or the pathways mediating cardiometabolic risk. These contributions are significant because they will demonstrate the need to begin interventions earlier in development and will identify novel treatment targets to mitigate future cardiometabolic risk and ultimately shift the odds for children experiencing ELS.

抽象的 心脏代谢健康不佳，包括心血管疾病和代谢疾病，是 全球可预防死亡的主要原因。越来越多的证据表明童年 暴露于压力会增加终生心脏代谢风险。拟议的研究涉及 4 美国心脏协会最近发现的文献中的空白：（1）需要 前瞻性研究，（2）需要更好地确定更容易受到压力的时期 关于心脏代谢健康，（3）需要更多关于机械途径的证据， (4) 需要进行更多探索性别差异的研究。我们的中心假设是 婴儿期是启动增加心脏代谢的运动过程的重要时期 疾病风险。我们的早期生活压力（ELS）模型将是孤儿院的经历 国际收养的儿童。我们将评估青春期的心脏代谢功能 这些评估与成人心血管健康相关的最早年龄阶段。 我们将把从孤儿院收养的婴儿或很小的青少年与 资源丰富的家庭，青少年在原生家庭中长大，受过同等教育， 收入。我们将解决三个具体目标：1）确定重要的关系之间的关系 生命最初几年的 ELS 和青春期的心脏代谢功能，2) 确定 介导或部分介导 ELS 与心脏代谢功能关联的因素 和青春期功能的变化，以及 3) 探索 ELS- 中的性别差异 心脏代谢风险关联。在第一个目标下，动脉僵硬度和空腹血糖， 将检查胰岛素和血脂水平。对于第二个目标，ELS 对 将通过改变压力的介质来检查青春期的心脏代谢功能 系统活动、免疫老化指数、躯干脂肪量增加和健康行为较差。 在第三个目标中，将检查目标 1 的结果中的性别差异以及与 目标 2 中的潜在调解者。这些目标基于重要的初步数据。影响 这项研究的目的将是（1）提高人们对生命最初几年的重要性的理解 心脏代谢健康，（2）更深入地表征机制和途径 其中ELS-心脏代谢风险被实例化以及（3）确定是否存在性别 介导心脏代谢风险的关联或途径存在差异。这些 贡献意义重大，因为它们将表明有必要开始干预 处于开发早期，并将确定新的治疗目标以减轻未来的心脏代谢 风险并最终改变儿童经历 ELS 的几率。