# Socioecological Determinants of Immunoepigenetic Signatures of Diabetes Risk in Indigenous Communities

> **NIH NIH R01** · UNIVERSITY OF HAWAII AT MANOA · 2022 · $667,476

## Abstract

PROJECT SUMMARY/ABSTRACT
Native Hawaiians and Pacific Islanders (NHPIs) experience a disproportionately higher prevalence of
cardiometabolic diseases, primarily Type-2 diabetes mellitus (DM), than other U.S. racial/ethnic populations.
Compared to White residents, NHPIs have a ~2.5-fold higher incidence and earlier onset of diagnosed DM with
significant differences in DM disparities appearing at age 35. NHPIs also have the lowest levels of educational
attainment, lowest mean income, highest rates of poverty, and higher exposures to DM risk factors compared to
other major racial/ethnic groups in Hawaii, and also reside in environments that include low neighborhood
socioeconomic status (nSES). The coincidence of disparities in DM prevalence and adverse social environments
implicate complex interactions that may impact gene pathways relevant to the onset of DM. However, the
interactions between the social environment and biological mechanism(s) that underlie DM health disparities of
NHPIs are unknown. The detrimental effects of social environments, such as nSES, may include an increased
prevalence of chronic low-grade inflammation known to contribute to DM. Epigenetic mechanisms (e.g. DNA
methylation) regulate transcription of pro-inflammatory genes of monocytes, a key mediator of inflammation. Our
preliminary data in NHPIs with DM that completed a lifestyle intervention revealed significant genome-wide
changes to the DNA methylation and gene expression states of pro-inflammatory genes that were associated
with their monocyte inflammatory activity and glycemic control. In another study, we observed significant
changes to the gut microbiome, dysbiosis of which may also be an underlying attribute of DM, in NHPI youth that
correlated with social network influences and health behaviors that modified their risk for DM. Lifestyle-
associated changes to the gut microbiome impacts DNA methylation through bioavailability of substrates
essential to the epigenetic machinery. Thus, we propose a hypothesis that the social environment conditions
the epigenomic landscape and gut microbiome composition that regulate inflammation and metabolic pathways
underlying DM. To test this hypothesis, we aim to identify an epigenetic signature of DM risk in monocytes from
a new cohort of NHPIs and that of their social networks, and examine associations with neighborhood- and
interpersonal-level social factors using a cross-sectional study design (Aim 1). We will then explore the
mechanistic basis to which this signature may underlie innate DM-relevant traits by examining associations with
inflammation, inflammatory activity, and gut microbiome composition/diversity (Aim 2). Finally, we will determine
the degree to which this signature may prospectively be predictive of DM outcome (Aim 3). Addressing these
aims will yield novel datasets of NHPIs in a health disparate population for determining the relationship between
the “immunoepigenetic-gut microbiome axis” and DM risk withi...

## Key facts

- **NIH application ID:** 10458062
- **Project number:** 5R01MD016593-02
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Alika Keolaokalani Maunakea
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $667,476
- **Award type:** 5
- **Project period:** 2021-07-28 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458062

## Citation

> US National Institutes of Health, RePORTER application 10458062, Socioecological Determinants of Immunoepigenetic Signatures of Diabetes Risk in Indigenous Communities (5R01MD016593-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10458062. Licensed CC0.

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