# Effects of prenatal exposures to maternal obesity and gestational diabetes on metabolic decline from childhood to adolescence and underlying neurobiological pathways

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $727,572

## Abstract

PROJECT SUMMARY/ABSTRACT
Rising childhood obesity rates are coupled with an alarming increase in the prevalence of type 2 diabetes in
children and adolescents. Evidence suggests that in utero exposures to maternal obesity and/or gestational
diabetes mellitus (GDM) contribute to these upward trends, and the effects of these prenatal exposures on
metabolic risk become more pronounced during adolescence. While the biological mechanisms of such
maternal-fetal programming are poorly understood, compelling studies in rodent models show that in utero
exposure to maternal obesity and/or diabetes causes abnormal development of brain pathways involved in
energy balance regulation, leading to obesity and type 2 diabetes later in life.
Our group was the first to study the effects in utero exposures to maternal obesity and GDM on brain pathways
and metabolic outcomes in humans using a pioneering approach combining neuroimaging methods and
metabolic phenotyping in children. To date, findings from cross-sectional studies in our BrainChild cohort
provide strong support for the neuroendocrine programming effects seen in animal models. The earliest
abnormality we have identified involves modification of brain pathways known to be involved in energy balance
regulation. These brain modifications were predictive of increases in food intake and weight gain in children
during short term follow-up and lead to the primary hypothesis of the present study: that differences in the
neural markers observed in children at age 7-10 will be predictive of metabolic outcomes during the transition
to adolescence, a critical time for brain development and metabolic decline. Child postnatal behaviors including
physical activity, diet and sleep may also be mediating or modifying the effects of brain pathways linking in
utero exposures to maternal GDM and obesity on child metabolic trajectories. We will include measures of
these behaviors and explore these pathways to generate important data for future studies focusing on lifestyle
behaviors.
The proposed longitudinal study of the BrainChild cohort for up to six years of follow up provides the unique
opportunity to advance our understanding of the interplay among brain changes, obesity, insulin resistance and
beta cell function at early stages in the evolution of transgenerational transmission of obesity and diabetes
risks. Given the growing number of pregnancies complicated by maternal obesity and GDM, the well-being of
future generations may depend to an important degree on developing interventions that can break the vicious
transgenerational cycle of obesity and diabetes. The proposed studies will contribute critical information to the
knowledge base required for development of such interventions.

## Key facts

- **NIH application ID:** 10682336
- **Project number:** 1R01DK134079-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Kathleen Alanna Page
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $727,572
- **Award type:** 1
- **Project period:** 2023-08-28 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10682336

## Citation

> US National Institutes of Health, RePORTER application 10682336, Effects of prenatal exposures to maternal obesity and gestational diabetes on metabolic decline from childhood to adolescence and underlying neurobiological pathways (1R01DK134079-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10682336. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*