R01MD016593

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. They also reside in environments that include low neighborhood socioeconomic status (NSES). The coincidence of disparities in DM prevalence and adverse social environments implicates 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.

University Of Hawaii

TO SUPPORT BASIC, CLINICAL, SOCIAL, AND BEHAVIORAL RESEARCH, PROMOTE RESEARCH INFRASTRUCTURE AND TRAINING, FOSTER EMERGING PROGRAMS, DISSEMINATE INFORMATION, AND REACH OUT TO MINORITY AND OTHER HEALTH DISPARITY COMMUNITIES. THE NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES (NIMHD) HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS: (1) THE CENTERS OF EXCELLENCE PROGRAM PROMOTES RESEARCH TO IMPROVE MINORITY HEALTH AND/OR REDUCE AND ELIMINATE HEALTH DISPARITIES, BUILDS RESEARCH CAPACITY FOR MINORITY HEALTH AND HEALTH DISPARITIES RESEARCH IN ACADEMIC INSTITUTIONS, ENCOURAGES PARTICIPATION OF HEALTH DISPARITY GROUPS AND COMMUNITIES IN BIOMEDICAL AND BEHAVIORAL RESEARCH AND PREVENTION AND INTERVENTION ACTIVITIES, AND BRINGS TOGETHER INVESTIGATORS FROM RELEVANT DISCIPLINES IN A MANNER THAT WILL ENHANCE AND EXTEND THE EFFECTIVENESS OF THEIR RESEARCH, (2) NIMHD RESEARCH ENDOWMENT PROGRAM BUILDS RESEARCH CAPACITY AND INFRASTRUCTURE AT ELIGIBLE NIMHD CENTERS OF EXCELLENCE OR ELIGIBLE SECTION 736 HEALTH PROFESSIONS SCHOOLS (42 U.S.C. 293) TO FACILITATE MINORITY HEALTH AND OTHER HEALTH DISPARITIES RESEARCH TO CLOSE THE DISPARITY GAP IN THE BURDEN OF ILLNESS AND DEATH EXPERIENCED BY RACIAL AND ETHNIC MINORITY AMERICANS AND OTHER HEALTH DISPARITY POPULATIONS, PROMOTES A DIVERSE AND STRONG SCIENTIFIC, TECHNOLOGICAL AND ENGINEERING WORKFORCE, AND EMPHASIZES THE RECRUITMENT AND RETENTION OF UNDERREPRESENTED MINORITIES AND OTHER SOCIO-ECONOMICALLY DISADVANTAGED POPULATIONS IN THE FIELDS OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND OTHER AREAS OF THE SCIENTIFIC WORKFORCE, (3) THE CENTERS OF EXCELLENCE ON ENVIRONMENTAL HEALTH DISPARITIES RESEARCH TO STIMULATE BASIC AND APPLIED RESEARCH ON ENVIRONMENTAL HEALTH DISPARITIES, (4) MINORITY HEALTH AND HEALTH DISPARITIES INTERNATIONAL RESEARCH TRAINING PROGRAM (MHIRT) AWARDS ENABLE U.S. INSTITUTIONS TO TAILOR SHORT-TERM BASIC SCIENCE, BIOMEDICAL AND BEHAVIORAL MENTORED STUDENT INTERNATIONAL RESEARCH TRAINING OPPORTUNITIES TO ADDRESS GLOBAL ISSUES RELATED TO UNDERSTANDING, REDUCING, AND ELIMINATING HEALTH DISPARITIES, (5) SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM INCREASES PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, ENCOURAGES SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTERS AND ENCOURAGES PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (6) SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTERS TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, INCREASES PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTERS AND ENCOURAGES PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (7) HEALTH DISPARITIES RESEARCH PROJECT GRANTS (RPG) SUPPORT INNOVATIVE PROJECTS TO ENHANCE OUR UNDERSTANDING OF BIOLOGICAL MECHANISMS, SOCIAL, BEHAVIORAL, AND HEALTH SERVICES THAT CAN DIRECTLY AND DEMONSTRABLY CONTRIBUTE TO THE IMPROVEMENT IN MINORITY HEALTH AND THE ELIMINATION OF HEALTH DISPARITIES WHICH INCLUDES THE (8) RESEARCH CENTERS IN MINORITY INSTITUTIONS (RCMI) BUILD CAPACITY FOR BASIC BIOMEDICAL AND/OR BEHAVIORAL RESEARCH, CLINICAL AND TRANSLATIONAL RESEARCH (RCTR) AND A NETWORK (RCTN) BY FOCUSING ON INSTITUTIONAL RESOURCE DEVELOPMENT, SUCH AS SUPPORTING CORE RESEARCH FACILITIES AND STAFF, PURCHASING ADVANCED INSTRUMENTATION, AND LABORATORY RENOVATIONS/ALTERATIONS (9) CLINICAL RESEARCH EDUCATION AND CAREER DEVELOPMENT (CRECD) AWARDS PROVIDE DIDACTIC TRAINING AND MENTORED CLINICAL RESEARCH EXPERIENCES TO DEVELOP INDEPENDENT RESEARCHERS WHO CAN LEAD CLINICAL RESEARCH STUDIES, ESPECIALLY THOSE ADDRESSING HEALTH DISPARITIES, (10) PATHWAY TO INDEPENDENCE AWARDS (K99/R00) TO INCREASE AND MAINTAIN A STRONG COHORT OF NEW AND TALENTED, NIH-SUPPORTED, INDEPENDENT INVESTIGATORS. (11) NIH RESEARCH CONFERENCE GRANT AND NIH RESEARCH CONFERENCE COOPERATIVE AGREEMENT PROGRAMS SUPPORT HIGH-QUALITY CONFERENCES THAT ARE RELEVANT TO THE MINORITY HEALTH AND HEALTH DISPARITIES, (12) TRANSDISCIPLINARY COLLABORATIVE CENTERS FOR HEALTH DISPARITIES RESEARCH COMPRISE REGIONAL COALITIONS OF ACADEMIC INSTITUTIONS, COMMUNITY ORGANIZATIONS, SERVICE PROVIDERS AND SYSTEMS, GOVERNMENT AGENCIES AND OTHER STAKEHOLDERS CONDUCTING COORDINATED RESEARCH, IMPLEMENTATION AND DISSEMINATION ACTIVITIES THAT TRANSCEND CUSTOMARY APPROACHES AND SILO ORGANIZATIONAL STRUCTURES TO ADDRESS CRITICAL QUESTIONS AT MULTIPLE LEVELS IN INNOVATIVE WAYS FOCUSED ON PRIORITY RESEARCH AREAS IN MINORITY HEALTH AND HEALTH DISPARITIES, (13) RUTH L. KIRSCHSTEIN NRSA INDIVIDUAL PREDOCTORAL FELLOWSHIP

93.307 - Minority Health and Health Disparities Research

National Institute for Minority Health and Health Disparities (NIMHD) [HHS - NIH]

Honolulu, Hawaii 968222318 United States

Single Zip Code

Social Epigenomics Research Focused on Minority Health and Health Disparities (R01-Clinical Trial Not Allowed) (PAR-19-372)

Amendment Since initial award the total obligations have increased 392% from $676,173 to $3,326,115.