Early childhood nutrition and adult metabolomic and cardiometabolic profiles

描述(申请人提供)：营养和感染是儿童成长和存活的关键决定因素。慢性炎症是成人心脏代谢性疾病的潜在决定因素，部分原因是终身传染病负担增加。这种风险通过改善早期生活中的营养而改变的可能性尚不清楚。我们的主要目的是确定早期营养的改善是否可以减轻心脏代谢风险的发展。我们将从INCAP(危地马拉)营养补充试验队列中收集新的数据。从1969-77年间，2392名儿童服用了高蛋白和卡路里补充剂阿托尔，或低卡路里饮料FRESCO，持续时间长达8年。与服用FRESCO的儿童相比，在生命的前3年服用阿托尔的儿童在童年时期成长得更好，从腹泻疾病发作中恢复得更快。我们前瞻性地跟踪了这一队列。我们建议重新联系队列中幸存的成员。队列将在38-53岁之间，这是评估心脏代谢风险的理想年龄。我们将进行临床检查，包括(在这个队列中第一次)收集心脏代谢风险的生物标记物。我们将分析样本中已建立的和新的生物标记物，包括高度创新的代谢组学。我们将更新和加强我们在以前的调查中收集的广泛的生命历程数据。我们将把新的数据与我们现有的RICH数据库联系起来，在社区随机试验的背景下，解决有关慢性营养不良和有效干预对抗营养不良对心脏代谢健康的长期影响的关键问题，该试验控制了原本难以解决的内源性问题。这项研究将是独一无二的，因为它有能力解决与成人健康的早期生活决定因素有关的未回答问题。这一前瞻性研究的队列已经达到了心脏代谢风险的流行率不可忽视的年龄。高生产率的研究团队在这一群体中的调查工作方面拥有丰富的经验，证明了跨研究波连接数据的能力，并在适当的现场方法、实验室方法和数据分析的统计方法方面拥有丰富的经验。由此产生的大量数据和样本库将提高队列对未来研究的价值。总而言之，这些因素确保了这项研究将处于有利地位，能够成功地解决人类健康和发展中未得到充分研究的关键问题。

DESCRIPTION (provided by applicant): Nutrition and infection are key determinants of child growth and survival. Chronic inflammation, which results in part from an increased lifetime burden of infectious disease, is an underlying determinant of adult cardiometabolic disease. The modifiability of this risk by improving nutrition in early life is unknown. Our principal objectiveis to determine whether improvements in early-life nutrition can attenuate the development of cardiometabolic risk. We will collect new data from the INCAP (Guatemala) Nutrition Supplementation Trial cohort. From 1969-77, 2392 children received atole, a high protein and calorie supplement, or fresco, a low calorie drink, for up to 8 y. Children who received atole in the first 3 y of life grew better in childhood and recovered more quickly from diarrheal illness episodes than did children who received fresco. We have followed this cohort prospectively. We propose to re-contact the surviving members of the cohort. The cohort will be 38-53 y old, an ideal age to assess cardiometabolic risk. We will conduct clinical examinations, including (for the first time in this cohort) collection of biomarkers of cardiometabolic risk. We will assay the samples for established and novel biomarkers, including highly innovative metabolomic profiling. We will update and enhance the extensive life-course data that we collected in previous surveys. We will link the new data to our existing rich database to address critical questions regarding the long-term effects on cardiometabolic health of both chronic under-nutrition and an effective intervention to combat under-nutrition, in the context of a community-randomized trial that controls for otherwise intractable questions of endogeneity. The study will be unique in its ability to address unanswered questions relating to early life determinants of adult health. This prospectively-studied cohort has reached an age where the prevalence of cardiometabolic risk is non-negligible. The highly productive research team has extensive experience with survey work among this cohort, demonstrated capacity to link data across study waves, and extensive experience with the appropriate field methods, laboratory methods, and statistical approaches to data analysis. The resulting extensive repository of data and samples will enhance the value of the cohort for future research. Taken together, these elements ensure that the study will be well positioned to successfully address critical understudied questions in human health and development.