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: 10396098
• 负责人: Megan R Gunnar
• 金额: $ 76.59万
• 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/10396098
• 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; Persons; 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 不良的心脏代谢健康，包括心血管和代谢性疾病，是 全球可预防死亡的主要原因。越来越多的证据表明童年 承受压力会增加寿命心脏代谢风险。拟议的研究解决了4 美国心脏协会最近确定的文献差距：（1）需要 前瞻性研究，（2）需要更好地指定更大脆弱性的时期 关于心脏代谢的健康，（3）需要更多关于机械途径的证据， （4）需要更多探索性别差异的研究。我们的中心假设是 婴儿期是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模型（ELS）将是由孤儿院养成的 儿童在国际上收养。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有关的最早年龄。 我们将比较被孤儿院的婴儿或非常小的孩子被收养的青少年 资源良好的房屋，青年在其出生的家庭中养育了可比的教育和 收入。我们将解决三个具体目标：1）确定重要的关系 ELS在生命的头几年和青春期心脏代谢功能，2）确定 介导或部分介导EL与心脏代谢功能的关联的因素 以及青春期功能的变化，以及3）探索ELS的性别差异 心脏代谢风险关联。在第一个目标下，动脉刚度和空腹葡萄糖， 将检查胰岛素和脂质水平。为了第二个目标，ELS对 在青春期的心脏代谢功能将与改变的介体一起检查 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，将在AIM 1的结果中检查性别差异，并与 AIM 2中的潜在介体。这些目标基于重要的初步数据。影响 这项研究将是（1）对生命最初几年对生命的重要性的了解 心脏代谢健康，（2）对机制和通路的更深入的表征 实例化了哪些ELS-核代谢风险以及（3）确定是否存在性 介导心脏代谢风险的关联或途径的差异。这些 贡献很重要，因为他们将证明需要开始干预措施 开发的早期，将确定新的治疗靶标，以减轻未来的心脏代谢 风险并最终改变了经历ELS的儿童的几率。