# Epigenetic Programming of Cardimetabolic Health during Childhood

> **NIH NIH P20** · UNIVERSITY OF HAWAII AT MANOA · 2021 · $225,167

## Abstract

High childhood adiposity has been associated with a greater risk of type II diabetes (T2DM), coronary 
heart disease, hypertension, and certain types of cancer in adulthood. Prior pediatric studies suggest that 
insulin resistance (IR) may amplify the influence of childhood adiposity on future cardiometabolic health. 
There is a critical need to understand predictors of childhood IR and how IR modifies the impact of 
adiposity on the developmental programming of adult disease. Increasing exposure to endocrine 
disrupting chemicals (EDCs) during critical windows of structural and functional development may be 
contributing to growing rates of both childhood obesity and IR. The mechanism mediating the prolonged 
influence of these exposures on growth patterns is poorly understood. We hypothesize childhood 
adiposity and IR impact patterns of DNA methylation (DNAm), and that these associations are partially 
shaped by EDC exposure. We plan to explore these relationships among a subset of females within the 
ongoing longitudinal Growth and Obesity Cohort Study based in Santiago, Chile. This well-characterized 
cohort has extensive exposure information and genome-wide buccal cell DNAm assays, as well as 
anthropometric measurements collected every 6 to 12 months. We will use this combined data to conduct 
three novel investigations. First, we propose to evaluate the association between childhood adiposity and 
pubertal DNAm. There is well-validated evidence of an association between body mass index and DNAm 
at hundreds of sites across the genome among adults. We are proposing the largest, and first longitudinal 
study of the association between childhood adiposity and adolescent DNAm. Second, we will identify 
patterns of adolescent DNAm that are associated with childhood IR. Numerous studies have identified 
site-specific associations between DNAm and T2DM. Far fewer have examined the relationship between 
DNAm and IR. This will be the first investigation among children and explore how IR modifies the 
relationship between adiposity and adolescent DNAm patterns. Finally, we will investigate patterns of 
DNAm associated with childhood EDC exposure, and evaluate the degree to which these relationships 
are mediated by adiposity and IR. Our extensive longitudinal data and comprehensive series of analyses 
will allow us to identify patterns of DNAm that may contribute to the early life programming of adult 
cardiometabolic health.

## Key facts

- **NIH application ID:** 10378461
- **Project number:** 5P20GM113134-05
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Alexandra Margaret Lynn Binder
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,167
- **Award type:** 5
- **Project period:** 2017-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378461

## Citation

> US National Institutes of Health, RePORTER application 10378461, Epigenetic Programming of Cardimetabolic Health during Childhood (5P20GM113134-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10378461. Licensed CC0.

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