# Social Immunoepigenetic Conditioning of Diabetes Disparities

> **NIH NIH U54** · UNIVERSITY OF HAWAII AT MANOA · 2021 · $886,381

## Abstract

Native Hawaiians and Pacific Islanders (NHs/PIs) experience a disproportionately higher prevalence
and earlier onset of cardiometabolic health outcomes, including Type-2 diabetes mellitus (DM) and
cardiovascular disease (CVD), than other racial/ethnic groups. These health disparities may result from the
social environment shaping an individual’s health behaviors (e.g. nutrition, physical activity, and education) and
physiological responses that may mediate gene-environment interactions. The detrimental effects of social
environments may include an increase in systemic inflammation, a hallmark of cardiometabolic diseases where
monocytes of the immune system play a major role. We observed neighborhood social environments that
associated with inflammation in vulnerable populations. Additionally, other studies show that monocyte-mediated
inflammation leads to insulin resistance in target cells and heightened risk of cardiometabolic
diseases. Epigenetic mechanisms, including DNA methylation, regulate transcription of pro-inflammatory
genes in monocytes. We posit that neighborhood social environment leads to global changes in DNA
methylation states in immune cells associated with cardiometabolic disease risk. In our work, we observed
significant genome-wide changes to DNA methylation and gene expression states of pro-inflammatory genes
that associated with monocyte inflammatory activity and glycemic control in DM patients, and a robust DNA
methylomic signature of insulin resistance in monocytes that correlated with CVD risk. Together, these data
suggest that cardiometabolic diseases may in part result from social environment-induced changes to the
epigenomic landscape in monocytes underlying their inflammatory states. In this study, we will address
whether the neighborhood social environment impacts epigenomic variability in monocytes across different
ethnic populations in Hawaii and account for cardiometabolic health disparities, specifically to that of DM in
NHs/PIs. To do so, we propose to integrate detailed individual-level health behavior, clinical/immunologic,
genetic, and monocyte-specific epigenomic data with neighborhood-level social environment data from our
Multiethnic Cohort Study (MEC). By using a population-based prospective study with viably preserved cells, we
will have an unprecedented opportunity to examine the translational utility of epigenomic information in
predicting clinically diagnosed DM that occurred during a 20-year follow-up. As NHs/PIs have
disproportionately high rates of DM, we anticipate an increased frequency of an immunoepigenetic signature
predictive of DM outcomes, which would provide novel insight into the etiology of health disparities. Therefore,
we believe our social epigenomic multiethnic study meets the overall goals of this FOA to advance the science
of epigenomics focused on health disparities, expand approaches for understanding epigenetic mechanisms
by which social factors lead to biological changes that a...

## Key facts

- **NIH application ID:** 10268258
- **Project number:** 5U54MD007601-35
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Alika Keolaokalani Maunakea
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $886,381
- **Award type:** 5
- **Project period:** 1997-09-01 → 2022-09-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10268258

## Citation

> US National Institutes of Health, RePORTER application 10268258, Social Immunoepigenetic Conditioning of Diabetes Disparities (5U54MD007601-35). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10268258. Licensed CC0.

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