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

肾素-血管紧张素-醛固酮系统、ARMC5 和脑啡肽酶在非裔美国人葡萄糖代谢中的作用

• 批准号: 10417078
• 负责人: Joshua J Joseph
• 金额: $ 18.71万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10417078
• 关键词: Address; Adrenal Cortex; African American population; Aldosterone; Angiotensin Receptor; Area; Armadillo Repeat; Award; Beta Cell; Biomedical Research; Blood Pressure; CYP11B2 gene; Cardiovascular Diseases; Cell physiology; Clinical Research; Clinical Trials; Closure by clamp; Development; Diabetes Mellitus; Diabetes prevention; Dose; Endocrinology; Endothelin-1; Epidemiology; European; Foundations; Functional disorder; Future; Gene Mutation; Genetic; Genomics; Glucose Clamp; Goals; Health; High Prevalence; Hormonal; Hormones; Hyperaldosteronism; Hyperglycemia; Hypertension; Incidence; Individual; Insulin Resistance; Intervention; Investigation; Jackson Heart Study; Knowledge; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolism; Methodology; Mutation; Neprilysin; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Ohio; Pathway interactions; Patients; Performance; Placebos; Plasma; Play; Population; Practice Guidelines; Prediabetes syndrome; Prevalence; Prevention; Prevention trial; Primary Hyperaldosteronism; Public Health; Regulation; Renin; Renin-Angiotensin-Aldosterone System; Research; Research Personnel; Research Proposals; Risk; Risk Factors; Role; Scientist; Skeletal Muscle; Sodium; System; Techniques; Testing; Therapeutic; Time; Training; Translating; Tumor Suppressor Genes; United States; Universities; Variant; Vasoconstrictor Agents; Woman; Work; antagonist; blood pressure regulation; career; causal model; clinical investigation; design; experience; fasting glucose; fasting plasma glucose; genetic analysis; genetic variant; glucose metabolism; glucose uptake; health disparity; high risk; impaired glucose tolerance; improved; inhibitor; insight; lifetime risk; mortality; new therapeutic target; novel; novel strategies; prevent; professor; racial and ethnic disparities; skills; valsartan

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 the contribution of the RAAS to changes in glucose metabolism in the development of T2DM. This work will lay the foundation to develop novel therapeutic targets for T2DM.

项目总结/文摘

项目成果

Association of Socioeconomic Status With Ideal Cardiovascular Health in Black Men.

• DOI: 10.1161/jaha.120.020184
• 发表时间: 2021-12-07
• 期刊: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• 影响因子: 5.4
• 作者: Azap, Rosevine A.;Nolan, Timiya S.;Gray, Darrell M., II;Lawson, Kiwan;Gregory, John;Capers, Quinn;Odei, James B.;Joseph, Joshua J.
• 通讯作者: Joseph, Joshua J.

Plasma adipokines and glycaemic progression among African Americans: Findings from the Jackson Heart Study.

• DOI: 10.1111/dme.14465
• 发表时间: 2021-05
• 期刊: DIABETIC MEDICINE
• 影响因子: 3.5
• 作者: Kaze, Arnaud D.;Musani, Solomon K.;Bidulescu, Aurelian;Joseph, Joshua J.;Correa, Adolfo;Ndumele, Chiadi E.;Bertoni, Alain G.;Ahima, Rexford S.;Golden, Sherita H.;Echouffo-Tcheugui, Justin B.
• 通讯作者: Echouffo-Tcheugui, Justin B.

Renin-Angiotensin-Aldosterone System, Glucose Metabolism and Incident Type 2 Diabetes Mellitus: MESA.

• DOI: 10.1161/jaha.118.009890
• 发表时间: 2018-09-04
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Joseph JJ;Echouffo Tcheugui JB;Effoe VS;Hsueh WA;Allison MA;Golden SH
• 通讯作者: Golden SH

Community engagement and clinical trial diversity: Navigating barriers and co-designing solutions-A report from the "Health Equity through Diversity" seminar series.

• DOI: 10.1371/journal.pone.0281940
• 发表时间: 2023
• 期刊: PloS one
• 影响因子: 3.7

Association Between Social Determinants of Health and Glycemic Control Among African American People with Type 2 diabetes: The Jackson Heart Study.

患有 2 型糖尿病的非洲裔美国人中健康的社会决定因素与血糖控制之间的关联：杰克逊心脏研究。

• DOI: 10.1093/abm/kaac026
• 发表时间: 2022
• 期刊: Annals of behavioral medicine : a publication of the Society of Behavioral Medicine
• 作者: Hu,Jie;Kline,DavidM;Tan,Alai;Zhao,Songzhu;Brock,Guy;Mion,LorraineC;Efird,JimmyT;Wang,Danxin;Sims,Mario;Wu,Bei;Mongraw-Chaffin,Morgana;Joseph,JoshuaJ
• 通讯作者: Joseph,JoshuaJ