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.
