# CREBRF and risk of pregnancy and postpartum dysglycemia in American Samoan women

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $1,007,897

## Abstract

PROJECT SUMMARY
As many as 42% of American Samoan women develop gestational diabetes (GDM) in pregnancy, which
substantially elevates their risk of progressing to Type 2 diabetes (T2DM). Genetic factors play a substantial
role in diabetes risk, underscoring the importance of utilizing genomic data for targeted screening, treatment,
and prevention. However, historical exclusion of PI populations from genetic research has hindered
advancements in inclusive precision health initiatives, particularly related to women's health. In >10 years of
research with Samoan communities our team identified a novel missense variant (rs373863828) in the
CREBRF gene that is common among Pacific Islanders, including American Samoans. The CREBRF variant is
associated with increased body mass, but is paradoxically protective against T2DM, making it an attractive
potential biomarker of diabetes risk. The impact of the CREBRF variant on GDM risk, progression to
postpartum T2DM, and the variant's mechanism of action remain unclear. However, preliminary data suggest
that CREBRF may protect against GDM and that the mechanism of protection may be improved insulin
secretion. To test these hypotheses, we will recruit a prospective cohort of 350 pregnant American Samoan
women enrolled in the first trimester and followed until 18 months postpartum. Through three pregnancy (10-14
weeks (w), 24-28w, and 32-26w) and four postpartum (6-12w, 6 months (m) 12 m, 18m) visits we will
comprehensively evaluate glucose homeostasis (frequently sampled oral glucose tolerance tests, HbA1c, and
continuous glucose monitoring) and insulin response. We will use cutting-edge statistical approaches to
examine how changes in glucose homeostasis and insulin secretion/action associated with CREBRF, which
are not currently captured by routine 24-28w oral glucose tolerance tests, influence GDM and postpartum
T2DM risk. Specifically, we will examine associations of CREBRF with glucose homeostasis during pregnancy
(Aim 1) and postpartum changes in glucose homeostasis and incident pre-DM/T2DM risk (Aim 2), whether
improved insulin secretion mediates the protective effect of CREBRF on diabetes risk (Aim 3), and explore the
connections between CREBRF, insulin secretion, and birth outcomes (Exploratory Aim 4). Our work has strong
potential to shift clinical practice and reduce diabetes disparities by proving insight into the potential for
CREBRF to serve as a genetic biomarker of GDM or T2DM risk. More broadly, uncovering important insight
into how the CREBRF variant regulates glucose homeostasis will inform future molecular studies to further
understand CREBRF's mechanism(s) of action, potentially leading to pharmacogenomic approaches and
future diabetes therapeutic targets for all populations. With expertise in epidemiology, diabetes, obstetrics,
endocrinology, and biostatistics, our team is ideally positioned to carry out this ground-breaking work to reduce
diabetes-related health disparities for American ...

## Key facts

- **NIH application ID:** 11047863
- **Project number:** 1R01DK139672-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Angela Bengtson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,007,897
- **Award type:** 1
- **Project period:** 2024-09-19 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11047863

## Citation

> US National Institutes of Health, RePORTER application 11047863, CREBRF and risk of pregnancy and postpartum dysglycemia in American Samoan women (1R01DK139672-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11047863. Licensed CC0.

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