# The Role of The Renin-Angiotensin-Aldosterone System, ARMC5, and Neprilysin in Glucose Metabolism among African Americans

> **NIH NIH K23** · OHIO STATE UNIVERSITY · 2021 · $53,466

## Abstract

PROJECT SUMMARY/ABSTRACT
Joshua J. Joseph, MD, is an Assistant Professor in the Division of
Endocrinology, Diabetes and Metabolism at The Ohio State University. Dr. Joseph seeks a Mentored Patient-
Oriented Research Career Development Award in order to obtain the skills, knowledge, and mentored
research experience that are essential for a career as a clinician scientist in the field of type 2 diabetes mellitus
(T2DM) prevention. This proposal is aimed at determining the role of the renin-angiotensin-aldosterone system
(RAAS) in glucose metabolism and the development of T2DM among African Americans (AAs). AAs are 1.7
times as likely to develop T2DM in the US and are twice as likely to die from T2DM compared to non-Hispanic
whites. Thus, this represents an area of critical need. The objectives of this proposal are to determine the role
of the RAAS, endothelin-1, ARMC5 (armadillo repeat containing 5) and RAAS antagonism in glucose
metabolism and the development of diabetes. The specific aims of this research proposal are: (1) to determine
the associations of aldosterone and endothelin-1, individually and combined, with HOMA-insulin resistance,
HOMA-β cell function, fasting plasma glucose and incident T2DM among AAs without T2DM at baseline in the
Jackson Heart Study (JHS); (2) to determine a) the cross-sectional associations of predicted damaging
ARMC5 mutations with plasma aldosterone, plasma renin activity, fasting glucose, and prevalent T2DM and b)
the longitudinal association with incident T2DM among AAs in the JHS; (3) to determine the impact of RAAS
antagonism or RAAS and neprilysin antagonism vs. placebo with changes in glucose metabolism over 6
months assessed via glucose clamp studies among AAs. For Aim 1, we propose predictive epidemiological
analyses in the JHS, an observational investigation of cardiovascular disease among AAs, to determine the
association of a combination of aldosterone and endothelin-1 with glucose metabolism, prevalent and incident
T2DM. For Aim 2, we propose genetic analyses in the JHS, to determine the association of ARMC5 genetic
variants with components of glucose metabolism, prevalent and incident T2DM. For Aim 3, we propose a 26-
week clinical trial to test the effect of RAAS antagonism on β-cell function and insulin resistance in AAs with
impaired glucose tolerance. The goals during the award period include developing expertise in the design,
performance, analysis and presentation of clinical research through mentored research, didactic coursework,
and formal training in clinical investigation of glucose metabolism, clinical trial methodology, genetic, genomic
and other –omic analytic techniques and predictive/causal modeling. Long-term career goals include
developing a career as an independent investigator focused on finding new approaches for preventing and
treating T2DM, particularly among historically understudied populations in biomedical research. The proposed
research aims to provide new insights into th...

## Key facts

- **NIH application ID:** 10413307
- **Project number:** 3K23DK117041-04S1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Joshua J Joseph
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $53,466
- **Award type:** 3
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413307

## Citation

> US National Institutes of Health, RePORTER application 10413307, The Role of The Renin-Angiotensin-Aldosterone System, ARMC5, and Neprilysin in Glucose Metabolism among African Americans (3K23DK117041-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10413307. Licensed CC0.

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