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

项目摘要 据估计，缺铁症（ID）影响着美国9%至16%的青春期女孩， 影响了非裔美国女孩ID，伴或不伴贫血，与认知功能下降有关， 运动能力下降，疲劳增加。无法识别的ID可能会发展为严重的并发症 贫血尽管口服铁剂的治疗很容易获得，但没有普遍的筛查建议， 以证据为基础的风险预测工具，以确定哪些女孩在其发展方面面临最高风险。早期识别 将允许设计良好的，长期的，对照的研究，评估筛查的影响 早期治疗对重要健康结果的影响。 本研究的目的是：1）确定在一个国家中ID的患病率，发病时间和危险因素。 青春期女孩的大型双胞胎队列;和2）通过全球血清分析鉴定ID的新生物标志物， 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标本，从国家心脏 肺和血液研究所（NHLBI）生长和健康研究（NGHS），肥胖风险因素的纵向研究 在非裔美国人和白人女孩中，从9-10岁到18-19岁每年随访一次。我们将分析 在连续时间点（第1年、第3年、第5年、第7年和第10年）从NGHS受试者中采集血清样本，其中至少4 在10年期间有样本（n=693）。我们将使用传统和 新的铁参数，包括血清铁蛋白和可溶性转铁蛋白受体1（sTfR 1），以确定 ID的患病率和时间，并评估预测ID发展的临床风险因素。我们将 对40份样本中的代谢物进行无偏分析，以表征ID与 非ID受试者，并将候选代谢物与标准铁参数进行比较，以找到可能使用的代谢物 作为少数民族和/或肥胖人群ID的预测标志物。 我们的研究团队在ID领域的流行病学和干预性研究的经验，方法学， 具有使用大型数据集的经验，以及执行大规模生物测定的跟踪记录，良好的位置 我们实现我们的目标。这项研究的结果将为风险预测工具的开发提供信息， 和基于证据的筛查建议，为ID在青春期女孩。鉴定相关代谢物 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 铁参数总体而言，这项工作需要提供证明未来R 01合理性的初步数据 应用程序，以充分评估ID筛查，治疗开始和随访的益处。结果将 直接解决美国卫生与公众服务部的健康人目标， 减少少女和年轻妇女的ID。

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.