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

种族、肥胖和代谢组学对年轻女性缺铁发展的探索

• 批准号: 10044001
• 负责人: Jacquelyn M Powers
• 金额: $ 12.78万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-20 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10044001
• 关键词: Address; Adolescence; Affect; African American; Age; Anemia; Biological Assay; Biological Markers; Blood Volume; Caucasians; Clinical Data; Controlled Study; Cross-Sectional Studies; Data; Development; Diagnosis; Dietary Iron; Early identification; Early treatment; Ethnic group; Evaluation; Fatigue; Female Adolescents; Ferritin; Future; Goals; Growth; Health; Hemorrhage; Homeostasis; Incidence; Individual; Inflammation; Intake; Intervention Studies; Iron; Laboratory Markers; Longitudinal Studies; Longitudinal cohort; Matched Group; Menarche; Methodology; Methods; Minority; National Heart, Lung, and Blood Institute; Neurocognitive; Obesity; Oral; Outcome; Patient-Focused Outcomes; Population; Positioning Attribute; Predictive Factor; Pregnancy Histories; Prevalence; Prognostic Marker; Prospective cohort; Questionnaires; Race; Randomized Controlled Trials; Research; Risk; Risk Factors; Sampling; Serum; Severities; Specimen; Study Subject; TFRC gene; Testing; Time; Time Study; United States; United States Dept. of Health and Human Services; Work; base; biracial; clinical risk; cognitive function; cohort; design; epidemiology study; evidence base; exercise capacity; experience; follow-up; girls; high risk; indexing; iron deficiency; large datasets; metabolomics; muscle form; novel; novel marker; obesity risk; predictive marker; prognostic; prognostic value; racial minority; screening; screening guidelines; tool; young woman

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.

项目概要 据估计，美国 9% 至 16% 的青春期女孩患有缺铁 (ID) 问题，且比例过高 影响非裔美国女孩。 ID，无论是否患有贫血，都与认知功能下降有关， 运动能力下降，疲劳感增加。无法识别的 ID 可能会发展为严重的并发症 贫血。尽管口服铁剂治疗很容易获得，但没有通用的筛查建议或 基于证据的风险预测工具，用于识别发育风险最高的女孩。早期识别 高危女孩的研究将允许进行精心设计的长期对照研究，以评估筛查的效果 及早治疗智力障碍对重要健康结果的影响。 该项目的研究目标是： 1) 确定人群中 ID 的患病率、发生时间和风险因素。 大量混血少女群体； 2) 通过全局血清分析来识别 ID 的新生物标志物 代谢组学。为了实现这一目标，我们将利用国家心脏中心的现有临床数据和标本 肺与血液研究所 (NHLBI) 生长与健康研究 (NGHS)，肥胖风险因素的纵向研究 每年对非洲裔美国女孩和白人女孩进行跟踪调查，从 9-10 岁到 18-19 岁。我们将化验 在连续时间点（第 1 年、第 3 年、第 5 年、第 7 年和第 10 年）从 NGHS 受试者中采集的血清样本，其中至少 4 10 年间可获得样本 (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 (sTfR1)，以确定 ID 的患病率和发生时间，并评估可预测 ID 发展的临床危险因素。我们将 对 40 个样品中的代谢物进行无偏分析，以表征 ID 与 ID 发生变化的代谢物 非 ID 受试者，并将候选代谢物与标准铁参数进行比较，以找到可以使用的代谢物 作为少数民族和/或肥胖人群 ID 的预测标记。 我们的研究团队在 ID、方法学领域的流行病学和介入研究方面拥有丰富的经验 使用大型数据集的经验，以及执行大规模生物测定、良好位置的跟踪记录 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 以及基于证据的青春期女孩智力障碍筛查建议。识别相关代谢物 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。总的来说，这项工作需要提供初步数据来证明未来 R01 的合理性 应用程序来全面评估身份筛查、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民目标 减少少女和年轻女性的智力障碍。