Elucidating the high and heterogeneous risk of gestational diabetes among Asian Americans: an integrative approach of metabolomics, lifestyles, and social determinants

阐明亚裔美国人妊娠期糖尿病的高且异质性风险：代谢组学、生活方式和社会决定因素的综合方法

• 批准号: 10804399
• 负责人: Liwei Chen
• 金额: $ 71.02万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-24 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10804399
• 关键词: Acculturation; Asian; Asian Americans; Asian population; Biological; California; Central obesity; Chinese; Clinical; Cohort Studies; Data; Diagnosis; Diet; Disparity; Electronic Health Record; Environment; Ethnic Origin; Ethnic Population; Filipino; Food; Functional disorder; Gestational Diabetes; Goals; Health; Heterogeneity; High Prevalence; Individual; Japanese; Knowledge; Language; Life Style; Mediating; Metabolic; Metabolic Pathway; Molecular; Neighborhoods; Not Hispanic or Latino; Participant; Pathway interactions; Physical activity; Population; Pregnancy; Pregnancy Complications; Prevalence; Prevention; Prevention strategy; Prospective cohort; Public Health Practice; Research; Resources; Risk; Risk Factors; Role; Sample Size; Sampling; Serum; Sleep; Social Environment; Socioeconomic Factors; Surveys; United States; United States National Institutes of Health; Validation; Vietnamese; Woman; Work; alpha-Fetoproteins; built environment; cohort; cost efficient; deprivation; design; early pregnancy; epidemiology study; ethnic disparity; health data; health equality; high risk; improve minority health; individualized prevention; lifestyle factors; metabolomics; novel; pregnant; programs; racial disparity; racial population; screening program; segregation; social determinants; social health determinants; socioeconomic disadvantage; systematic review; tool; treatment strategy

PROJECT SUMMARY/ABSTRACT Gestational diabetes mellitus (GDM), one of the most common and growing complications in pregnancy, presents striking racial and ethnic disparities. Asian American women are twice as likely to have GDM as non- Hispanic White women and there is also substantial heterogeneity in GDM rates across Asian subpopulations. The molecular mechanisms and upstream determinants for the high and heterogeneous risk of GDM across Asian subpopulations remain largely understudied since they are under-represented in health research. As one of the fastest-growing racial and ethnic groups in the US, it is crucial to better understand the molecular differences and similarities across Asian subpopulations to help elucidate the pathophysiology underlying their high and heterogeneous risk of GDM. Metabolomics is a powerful tool for comprehensively evaluating global metabolic signatures and understanding biological pathways. However, metabolomics studies among pregnant individuals are still limited and most have no or few Asian Americans. This study aimed to fill the current data and knowledge gaps for GDM disparity research by using a highly cost-efficient design that leverages the existing and unique resources: the California (CA) Alpha-fetoprotein Screening Program (CA-AFSP) and the Pregnancy Environment and Lifestyle Study (PETALS). In the discovery sample from the CA-AFSP program which covers >74% of the pregnant individuals in Southern CA, we propose to perform integrated untargeted and targeted metabolomic profiling using stored serum samples collected in early-mid pregnancy (15-19 gestational weeks) from 1500 individuals of four Asian subpopulations (i.e., 375 each of Chinese, Filipinos, Indian, and Vietnamese). We will identify metabolomic signatures in early-mid pregnancy associated with GDM in the CA-AFSP program and determine which metabolites and pathways overlap across all Asian Americans or distinguish across Asian subpopulations (Aim 1). We will construct an external validation set from the above four Asian subpopulations who participated in the PETALS cohort at Kaiser Permanente Northern CA. The PETALS is a well-characterized cohort with anthropometrics, multi-domain survey data, comprehensive health data from state-of-the-art electronic health records, and serum metabolomics assessed at 16-19 gestational weeks. We will validate GDM- related metabolomic signatures in the PETALS cohort for all Asian Americans and each Asian subpopulation (Aim 2) and examine associations of upstream lifestyles and social determinants of health (SDOHs) with GDM risk and metabolic signatures and whether metabolomic signatures partially mediate the association between upstream lifestyles and SDOHs with GDM risk (Aim 3). As the largest-scale study to date, our integrative approach encompassing metabolomics, lifestyles, and SDOHs provides an unparalleled opportunity to elucidate mechanisms of the drastic racial and ethnic disparities in GDM and to inform precision preventions for the high- risk, heterogeneous Asian subpopulations. Thus, this study has the potential to improve minority health and health equality in our nation.

项目摘要/摘要 妊娠期糖尿病（GDM）是妊娠期最常见和日益严重的并发症之一， 呈现出明显的种族和民族差异。亚裔美国妇女患GDM的可能性是非亚裔美国妇女的两倍。 西班牙裔白色女性和亚洲亚群的GDM发生率也有很大的异质性。 GDM高风险和异质性风险的分子机制和上游决定因素 亚洲亚群在很大程度上仍然没有得到充分研究，因为他们在健康研究中的代表性不足。作为一个 在美国增长最快的种族和民族群体中，更好地了解分子生物学是至关重要的。 亚洲亚群之间的差异和相似之处，以帮助阐明其潜在的病理生理学， GDM高风险和异质性风险。代谢组学是全面评价全球性疾病的有力工具， 代谢特征和理解生物学途径。然而，在孕妇中进行的代谢组学研究 亚裔美国人仍然有限，大多数人没有或很少有亚裔美国人。本研究旨在填补现有数据 和知识差距，GDM差距研究，通过使用一个高成本效益的设计，利用现有的 和独特的资源：加州（CA）甲胎蛋白筛查计划（CA-AFSP）和妊娠 环境与生活方式研究（PETALS）在CA-AFSP程序的发现示例中， >74%的孕妇在南加州，我们建议进行综合非靶向和靶向 使用在妊娠早期-中期（15-19孕周）收集的储存血清样本进行代谢组学分析 来自四个亚洲亚群的1500个个体（即，中国人、菲律宾人、印度人和越南人各375人）。 我们将在CA-AFSP项目中确定与GDM相关的妊娠早中期代谢组学特征 并确定哪些代谢物和途径在所有亚裔美国人中重叠，或在亚裔美国人中区分 亚群（目标1）。我们将从上述四个亚洲亚群构建外部验证集 他们参加了在加利福尼亚州北方凯撒医疗机构的PETALS队列。PETALS是一种特征鲜明的 具有人体测量学、多领域调查数据、来自最新技术水平的综合健康数据的队列 电子健康记录和在16-19孕周评估的血清代谢组学。我们将验证GDM- PETALS队列中所有亚裔美国人和每个亚裔亚群的相关代谢组学特征 (Aim 2）并检查上游生活方式和健康的社会决定因素（SDOH）与GDM的关联 风险和代谢特征以及代谢组学特征是否部分介导了 上游生活方式和SDOH与GDM风险（目标3）。作为迄今为止最大规模的研究，我们的综合 包括代谢组学、生活方式和SDOH的方法提供了一个无与伦比的机会来阐明 在GDM中严重的种族和民族差异的机制，并告知高精度预防， 风险，异质性亚洲亚群。因此，这项研究有可能改善少数民族的健康， 我们国家的健康平等。