Early childhood nutrition and adult metabolomic and cardiometabolic profiles

描述（由申请人提供）：营养和感染是儿童生长和生存的关键决定因素。慢性炎症是成人心脏代谢疾病的潜在决定因素，部分原因是终生感染传染病的负担增加。在生命早期通过改善营养来改变这种风险的可能性尚不清楚。我们的主要目的是确定早期营养的改善是否可以降低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年到1977年，有2392名儿童在长达8年的时间里服用了高蛋白质和高热量补充剂atole或低热量饮料fresco。在生命的前30岁服用atole的儿童在童年时期生长得更好，从腹泻疾病发作中恢复得比服用fresco的儿童更快。我们对这群人进行了前瞻性随访。我们建议重新联系幸存的同伴。研究对象年龄为38-53岁，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（在该队列中首次）收集心脏代谢风险的生物标志物。我们将分析样品中已建立的和新的生物标志物，包括高度创新的代谢组学分析。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过程数据。我们将把新数据与我们现有的丰富数据库联系起来，以解决关于慢性营养不良对心脏代谢健康的长期影响和对抗营养不良的有效干预的关键问题，在一个社区随机试验的背景下，控制其他棘手的内生性问题。这项研究将是独一无二的，因为它有能力解决与成年健康的早期生活决定因素有关的未解问题。这一前瞻性研究的队列已经达到了心脏代谢风险不可忽视的年龄。高生产力的研究团队在这一队列的调查工作方面拥有丰富的经验，展示了跨研究波数据联系的能力，以及在适当的现场方法、实验室方法和数据分析统计方法方面的丰富经验。由此产生的大量数据和样本将提高该队列对未来研究的价值。综上所述，这些因素确保这项研究能够成功地解决人类健康和发展中尚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.