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.

项目概要/摘要 妊娠糖尿病（GDM）是妊娠期最常见且日益严重的并发症之一， 呈现出显着的种族和民族差异。亚裔美国女性患 GDM 的可能性是非亚裔女性的两倍 西班牙裔白人女性和亚洲亚裔人群的 GDM 发生率也存在很大的异质性。 GDM高风险和异质性的分子机制和上游决定因素 由于亚洲亚人群在健康研究中的代表性不足，因此在很大程度上仍没有得到充分研究。作为一个 作为美国增长最快的种族和族裔群体，更好地了解分子生物学至关重要 亚洲亚人群之间的差异和相似之处，以帮助阐明其病理生理学基础 GDM 的高风险和异质性。代谢组学是综合评估全球代谢组学的强大工具 代谢特征和了解生物途径。然而，孕妇的代谢组学研究 个人数量仍然有限，而且大多数没有或很少有亚裔美国人。本研究旨在填补现有数据 通过利用现有的高成本效益设计，弥补 GDM 差异研究的知识差距 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 计划的发现样本中，其中涵盖 对于加利福尼亚州南部 >74% 的怀孕个体，我们建议进行综合的非针对性和针对性的 使用妊娠早期中期（妊娠 15-19 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 个人（即中国人、菲律宾人、印度人和越南人各 375 人）。 我们将在 CA-AFSP 项目中鉴定与 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洲人中区分 亚人群（目标 1）。我们将从上述四个亚洲亚人群中构建一个外部验证集 参加了北加州 Kaiser Permanente 的 PETALS 队列。 PETALS 是一个很有特色的 人体测量学队列、多领域调查数据、来自最先进的综合健康数据 电子健康记录和妊娠 16-19 周时评估的血清代谢组学。我们将验证 GDM- 所有亚裔美国人和每个亚裔亚群的 PETALS 队列中的相关代谢组学特征 （目标 2）并检查上游生活方式和健康社会决定因素 (SDOH) 与 GDM 的关联 风险和代谢特征以及代谢组特征是否部分介导两者之间的关联 具有 GDM 风险的上游生活方式和 SDOH（目标 3）。作为迄今为止最大规模的研究，我们的综合研究 涵盖代谢组学、生活方式和 SDOH 的方法提供了无与伦比的机会来阐明 GDM 中严重的种族和民族差异的机制，并为高风险人群的精准预防提供信息 风险，异质亚洲亚人群。因此，这项研究有可能改善少数民族的健康和 我们国家的健康平等。