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 妊娠糖尿病（GDM），妊娠中最常见和越来越多的并发症之一， 呈现出惊人的种族和种族差异。亚裔美国妇女的GDM的可能性是 西班牙裔白人妇女，在亚洲亚洲人群中GDM率也存在很大的异质性。 GDM的高和异质风险的分子机制和上游决定因素 亚洲亚群在健康研究中的代表性不足，因此在很大程度上仍在研究。作为一个 在美国增长最快的种族和族裔中，更好地了解分子至关重要 亚洲亚种群之间的差异和相似性，以帮助阐明其基础的病理生理学 GDM的高和异质风险。代谢组学是用于全面评估全球的强大工具 代谢特征和了解生物途径。但是，怀孕的代谢组学研究 个人仍然有限，大多数人没有或没有亚裔美国人。这项研究旨在填写当前数据 以及通过使用高度成本效益的设计来利用现有的高效设计，用于GDM差异研究的知识差距 和独特的资源：加利福尼亚（CA）Alpha-Fetoprotoin筛查计划（CA-AFSP）和怀孕 环境和生活方式研究（花瓣）。在CA-AFSP程序的发现样本中 > 74％的CA南部孕妇，我们建议执行综合的非目标和针对性的综合 使用在早期妊娠早期收集的储存的血清样品（15-19妊娠周）中的代谢组学分析（妊娠周） 从四个亚洲亚种群中的1500个人（即375个中国人，菲律宾人，印度和越南人）。 我们将确定与CA-AFSP计划中与GDM相关的早期怀孕中的代谢组学特征 并确定哪些代谢产物和途径在所有亚裔美国人中重叠或在亚洲地区区分 亚群（目标1）。我们将从上述四个亚洲亚群中构建外部验证集 参加了Kaiser Permanente Northern Ca的花瓣队列。花瓣是一个很好的特征 与人类学，多域调查数据，最先进的全面健康数据的队列 电子健康记录和血清代谢组学在16-19胎周评估。我们将验证GDM- 所有亚裔美国人和每个亚洲亚洲人群的花瓣队列中相关代谢组签名 （AIM 2）并检查上游生活方式和健康的社会决定因素（SDOHS）与GDM的关联 风险和代谢特征以及代谢组签名是否部分介导 具有GDM风险的上游生活方式和SDOHS（AIM 3）。作为迄今为止最大规模的研究，我们的综合性 涵盖代谢组学，生活方式和SDOHS的方法提供了无与伦比的机会来阐明 GDM中剧烈的种族和种族差异的机制，并为高度预防措施 风险，异质亚洲亚种群。因此，这项研究有可能改善少数民族健康和 我们国家的健康平等。