Exploration of Race, Obesity, and Metabolomics on the Development of Iron Deficiency in Young Women

项目总结 据估计，美国9%至16%的青春期女孩受缺铁(ID)的影响，而且不成比例 影响非裔美国女孩。无论有没有贫血，ID都与认知功能下降有关， 运动能力减弱，疲劳感增加。未被识别的ID可进展为严重的并发症 贫血。尽管口服铁治疗很容易获得，但没有普遍的筛查建议或 以证据为基础的风险预测工具，以确定哪些女孩的发育风险最高。早期识别 对高危女孩的筛查将允许进行设计良好的长期对照研究，评估筛查的效果 对ID的治疗和早期治疗对重要健康结局的影响。 本项目的研究目的是：1)确定艾滋病的患病率、发病时机和危险因素。 青春期女孩的大规模混血队列；以及2)通过全球血清分析确定ID的新生物标记物 代谢组学。为了实现这一目标，我们将利用现有的临床数据和国家心脏的样本 肺和血液研究所(NHLBI)生长与健康研究(NGHS)，肥胖危险因素的纵向研究 在非裔美国人和高加索人中，女孩的年龄从9-10岁到18-19岁每年都在跟踪。我们将进行化验 在连续时间点(1年、3年、5年、7年和10年)从至少4岁的NGHS受试者中采集血清样本 在10年期间可获得样本(n=693)。我们将同时使用传统和 新的铁参数，包括血清铁蛋白和可溶性转铁蛋白受体1(STfR1)，以确定 ID的患病率和发生时间，并评估预测ID发展的临床危险因素。我们会 对40个样本中的代谢物进行无偏分析，以确定ID与 并将候选代谢物与标准铁参数进行比较，以找出可能使用的代谢物 在少数民族和/或肥胖人群中作为ID的预测标志。 我们的研究团队在流行病学和干预性研究方面的经验 有使用大型数据集的经验，有进行大规模生物检测的记录，位置良好 来实现我们的目标。这项研究的结果将为风险预测工具的开发提供参考 和基于证据的青春期女孩ID筛查建议。确定相关的代谢物 与标准相比，ID将证实候选代谢物作为ID生物标志物的预后价值 熨斗参数。总体而言，这项工作需要提供证明未来R01合理的初步数据 应用程序，以全面评估ID筛查、治疗启动和随访的好处。结果将会是 直接满足美国卫生与公众服务部的健康人群目标 减少青春期女孩和年轻妇女的缺乏症。

PROJECT SUMMARY Iron deficiency (ID) affects an estimated 9 to 16% of adolescent girls in the United States and disproportionately affects African American girls. ID, with and without anemia, is associated with decreased cognitive function, diminished exercise capacity, and increased fatigue. Unrecognized ID can progress to complications of severe anemia. Despite readily available therapy with oral iron, there are no universal screening recommendations or evidence-based risk prediction tools to identify those girls at highest risk for its development. Early identification of at-risk girls would allow for well-designed, long-term, controlled studies that evaluate the effects of screening for and early treatment of ID on important health outcomes. The research aims of this project are to: 1) determine the prevalence of, timing of, and risk factors for ID in a large, biracial cohort of adolescent girls; and 2) identify novel biomarkers of ID through global serum profiling by metabolomics. To achieve this goal, we will utilize existing clinical data and specimens from the National Heart Lung and Blood Institute (NHLBI) Growth and Health Study (NGHS), a longitudinal study of obesity risk factors in African American and Caucasian girls followed annually from age 9-10 years to 18-19 years. We will assay serum samples drawn at serial time points (Years 1, 3, 5, 7, and 10) from NGHS subjects for whom at least 4 samples are available (n=693) over the 10-year period. We will determine ID status using both traditional and novel iron parameters, including serum ferritin and soluble transferrin receptor 1 (sTfR1) to determine the prevalence and timing of ID and assess clinical risk factors that are predictive of the ID development. We will perform unbiased profiling of metabolites in 40 samples to characterize metabolites that are altered in ID versus non-ID subjects and compare candidate metabolites to standard iron parameters to find those that may be used as predictive markers of ID in minority and/or obese populations. Our research team’s experience in epidemiologic and interventional studies in the field of ID, methodologic experience with the use of large datasets, and track record of performing large-scale bioassays, well-positions us to achieve our objectives. The results from this study will inform both the development of a risk prediction tool and evidenced-based screening recommendations for ID in adolescent girls. Identifying metabolites associated with ID will substantiate the prognostic value of candidate metabolites as biomarkers of ID compared to standard iron parameters. Overall, this work is required to provide the preliminary data that justifies a future R01 application to fully assess the benefits of ID screening, treatment initiation, and follow-up. The results will directly address the U.S. Department of Health and Human Services’ Healthy People objective of reducing ID in adolescent girls and young women.