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Socioecological Determinants of Immunoepigenetic Signatures of Diabetes Risk in Indigenous Communities

Award Number: R01MD016593
ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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 within the context of the social environment and provide new insight into the etiology of DM disparities in NHPIs, with generalizable implications for improving early identification of DM to enable preventative strategies in populations suffering from social/health inequities.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $647,296 )
2024	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	000	4	5/1/2024	NON-COMPETING CONTINUATION	$647,296
														Subtotal = $647,296

Issue Date FY: 2023 ( Subtotal = $667,856 )
2023	2023	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	000	3	4/21/2023	NON-COMPETING CONTINUATION	$667,856
2023	2023	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	001	3	8/7/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $667,856

Issue Date FY: 2022 ( Subtotal = $667,476 )
2022	2022	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	001	2	4/29/2022	NON-COMPETING CONTINUATION	$66,750
2022	2022	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	000	2	3/31/2022	NON-COMPETING CONTINUATION	$600,726
														Subtotal = $667,476

Issue Date FY: 2021 ( Subtotal = $676,173 )
2021	2021	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Minority Health and Health Disparities Research	000	1	7/28/2021	NEW	$676,173
														Subtotal = $676,173

Grand Total All Awards = $2,658,801

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Socioecological Determinants of Immunoepigenetic Signatures of Diabetes Risk in Indigenous Communities

Award Number: R01MD016593

ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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