Literature DB >> 22865897

Nonmodulation as the mechanism for salt sensitivity of blood pressure in individuals with hypertension and type 2 diabetes mellitus.

Patricia C Underwood1, Bindu Chamarthi, Jonathan S Williams, Anand Vaidya, Rajesh Garg, Gail K Adler, Marissa P Grotzke, Gitana Staskus, Devendra Wadwekar, Paul N Hopkins, Claudio Ferri, Anthony McCall, Donald McClain, Gordon H Williams.   

Abstract

CONTEXT: It is assumed that in individuals with type 2 diabetes mellitus (T2DM), blood pressure sensitivity to salt intake and the frequency of a low renin state are both increased compared with the nondiabetic population. However, studies supporting these assumptions may have been confounded by participant inclusion criteria, and study results may reflect target organ damage.
OBJECTIVE: The objective of this study was to examine in a cohort of T2DM 1) the frequency of salt sensitivity of blood pressure and 2) whether alterations of the renin-angiotensin-aldosterone system (RAAS) contribute to salt sensitivity in this population. DESIGN, PATIENTS, AND METHODS: Within participants of the HyperPATH cohort, four groups were analyzed: 1) T2DM with hypertension (HTN), n=51; 2) T2DM without HTN, n=30; 3) HTN only, n=451; and 4) normotensive, n=209. Phenotype studies were conducted after participants completed two dietary phases: liberal sodium (200 mmol/d) and low sodium (10 mmol/d) for 7 d each. Participants were admitted overnight to a clinical research center after each diet, and supine measurements of the RAAS before and after a 60-min angiotensin II infusion (3 ng/kg·min) were obtained.
RESULTS: Multivariate regression analysis demonstrated that T2DM status (all individuals with T2DM vs. individuals without T2DM) was not associated with the change in mean arterial pressure between the low and liberal sodium diets after accounting for age, gender, body mass index, race, and baseline blood pressure (T2DM status, P=0.5). Furthermore, two intermediate phenotypes of altered RAAS, low renin, and nonmodulation (NMOD), were associated with salt-sensitive blood pressure but occurred at different frequencies in the T2DM-HTN and HTN groups (low renin, 12% T2DM-HTN vs. 29% HTN; NMOD, 41% T2DM-HTN vs. 27% HTN; P=0.01).
CONCLUSION: The frequency of NMOD in participants with T2DM was significantly higher compared with HTN, suggesting that the salt sensitivity often seen in T2DM is driven by NMOD.

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Year:  2012        PMID: 22865897      PMCID: PMC3462947          DOI: 10.1210/jc.2012-2127

Source DB:  PubMed          Journal:  J Clin Endocrinol Metab        ISSN: 0021-972X            Impact factor:   5.958


  39 in total

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2.  Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients: validity of a new (MDRD) prediction equation.

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3.  Salt sensitivity, pulse pressure, and death in normal and hypertensive humans.

Authors:  M H Weinberger; N S Fineberg; S E Fineberg; M Weinberger
Journal:  Hypertension       Date:  2001-02       Impact factor: 10.190

4.  Blunted suppression of plasma renin activity in diabetes.

Authors:  M S Gordon; D A Price; N K Hollenberg
Journal:  J Renin Angiotensin Aldosterone Syst       Date:  2000-09       Impact factor: 1.636

5.  The paradox of the low-renin state in diabetic nephropathy.

Authors:  D A Price; L E Porter; M Gordon; N D Fisher; J M De'Oliveira; L M Laffel; D R Passan; G H Williams; N K Hollenberg
Journal:  J Am Soc Nephrol       Date:  1999-11       Impact factor: 10.121

6.  Increased insulin resistance in salt sensitive essential hypertension.

Authors:  V Giner; A Coca; A de la Sierra
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7.  Importance of the renin system for determining blood pressure fall with acute salt restriction in hypertensive and normotensive whites.

Authors:  F J He; N D Markandu; G A MacGregor
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8.  National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

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9.  Influence of dietary sodium on the renin-angiotensin-aldosterone system and prevalence of left ventricular hypertrophy by EKG criteria.

Authors:  J S Williams; G H Williams; X Jeunemaitre; P N Hopkins; P R Conlin
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10.  Genetic determinants of nonmodulating hypertension.

Authors:  Natapong Kosachunhanun; Steven C Hunt; Paul N Hopkins; Roger R Williams; Xavier Jeunemaitre; Pierre Corvol; Claudio Ferri; Richard M Mortensen; Norman K Hollenberg; Gordon H Williams
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  11 in total

1.  Effect of low salt diet on insulin resistance in salt-sensitive versus salt-resistant hypertension.

Authors:  Rajesh Garg; Bei Sun; Jonathan Williams
Journal:  Hypertension       Date:  2014-09-02       Impact factor: 10.190

2.  The influence of sodium- and calcium-regulatory hormone interventions on adipocytokines in obesity and diabetes.

Authors:  Anand Vaidya; Patricia C Underwood; Justin P Annes; Bei Sun; Gordon H Williams; John P Forman; Jonathan S Williams
Journal:  Metabolism       Date:  2012-11-09       Impact factor: 8.694

Review 3.  Salt Restriction in Diabetes.

Authors:  Peter M Clifton; Jennifer B Keogh
Journal:  Curr Diab Rep       Date:  2015-09       Impact factor: 4.810

4.  Dysregulated aldosterone secretion in persons of African descent with endothelin-1 gene variants.

Authors:  Jia W Tan; Tina Gupta; Worapaka Manosroi; Tham M Yao; Paul N Hopkins; Jonathan S Williams; Gail K Adler; Jose R Romero; Gordon H Williams
Journal:  JCI Insight       Date:  2017-12-07

5.  Abnormal aldosterone physiology and cardiometabolic risk factors.

Authors:  Anand Vaidya; Patricia C Underwood; Paul N Hopkins; Xavier Jeunemaitre; Claudio Ferri; Gordon H Williams; Gail K Adler
Journal:  Hypertension       Date:  2013-02-11       Impact factor: 10.190

Review 6.  Genetics of Human Primary Hypertension: Focus on Hormonal Mechanisms.

Authors:  Worapaka Manosroi; Gordon H Williams
Journal:  Endocr Rev       Date:  2019-06-01       Impact factor: 19.871

7.  Aldosterone dysregulation with aging predicts renal vascular function and cardiovascular risk.

Authors:  Jenifer M Brown; Patricia C Underwood; Claudio Ferri; Paul N Hopkins; Gordon H Williams; Gail K Adler; Anand Vaidya
Journal:  Hypertension       Date:  2014-03-24       Impact factor: 10.190

8.  Renin Phenotypes Characterize Vascular Disease, Autonomous Aldosteronism, and Mineralocorticoid Receptor Activity.

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Journal:  J Clin Endocrinol Metab       Date:  2017-06-01       Impact factor: 5.958

9.  Salt restriction lowers blood pressure at rest and during exercise without altering peripheral hemodynamics in hypertensive individuals.

Authors:  Stephen M Ratchford; Ryan M Broxterman; D Taylor La Salle; Oh Sung Kwon; Song-Young Park; Paul N Hopkins; Russell S Richardson; Joel D Trinity
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10.  Age-Related Autonomous Aldosteronism.

Authors:  Kazutaka Nanba; Anand Vaidya; Gordon H Williams; Isabel Zheng; Tobias Else; William E Rainey
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