Renin-angiotensin-aldosterone system, glucose metabolism and incident type 2 diabetes mellitus: MESA

Joshua J. Joseph, Justin Echouffo Tcheugui, Valery S. Effoe, Willa A. Hsueh, Matthew A. Allison, Sherita Hill Golden

Research output: Contribution to journalArticle

Abstract

Background—Mechanistic studies suggest that aldosterone impairs glucose metabolism. We investigated the cross-sectional associations of aldosterone and plasma renin activity with fasting plasma glucose, insulin resistance (IR), β-cell function, and longitudinal association with incident diabetes mellitus among adults in MESA (the multiethnic study of atherosclerosis) prospective cohort study. Methods and Results—Homeostatic model assessment of IR (HOMA2-IR) and HOMA2-β were used to estimate IR and β-cell function, respectively. Incident diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dL or anti-diabetic medication use at follow-up. Linear regression was used to examine cross-sectional associations of aldosterone with fasting plasma glucose, HOMA2-IR and HOMA2-β; Cox regression was used to estimate hazard ratios (HR) for incident diabetes mellitus with multivariable adjustment. There were 116 cases of incident diabetes mellitus over 10.5 years among 1570 adults (44% non-Hispanic white, 13% Chinese American, 19% Black, 24% Hispanic American, mean age 64±10 years, 51% female). A 100% increase in log-aldosterone was associated with a 2.6 mg/dL higher fasting plasma glucose, 15% higher HOMA2-IR and 6% higher HOMA2-β (P<0.01). A 1-SD increase in log-aldosterone was associated with a 44% higher risk of incident diabetes mellitus (P<0.01) with the greatest increase of 142% (P<0.01) observed in Chinese Americans (P for interaction=0.09 versus other ethnicities). Similar cross-sectional findings for log-plasma renin activity existed, but log-plasma renin activity was not associated with incident diabetes mellitus after full adjustment. Conclusions—Aldosterone is associated with glucose homeostasis and diabetes mellitus risk with graded associations among Chinese Americans and blacks, suggesting that pleiotropic effects of aldosterone may represent a modifiable mechanism in diabetes mellitus pathogenesis with potential racial/ethnic variation.

Original languageEnglish (US)
Article numbere009890
JournalJournal of the American Heart Association
Volume7
Issue number17
DOIs
StatePublished - Sep 1 2018

Fingerprint

Renin-Angiotensin System
Type 2 Diabetes Mellitus
Atherosclerosis
Diabetes Mellitus
Aldosterone
Insulin Resistance
Glucose
Asian Americans
Fasting
Renin
Social Adjustment
Hispanic Americans
Linear Models
Homeostasis
Cohort Studies
Prospective Studies

Keywords

  • Aldosterone
  • Race and ethnicity
  • Renin angiotensin system
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Renin-angiotensin-aldosterone system, glucose metabolism and incident type 2 diabetes mellitus : MESA. / Joseph, Joshua J.; Echouffo Tcheugui, Justin; Effoe, Valery S.; Hsueh, Willa A.; Allison, Matthew A.; Golden, Sherita Hill.

In: Journal of the American Heart Association, Vol. 7, No. 17, e009890, 01.09.2018.

Research output: Contribution to journalArticle

@article{8016412c371c40449ee613038ec41ebb,
title = "Renin-angiotensin-aldosterone system, glucose metabolism and incident type 2 diabetes mellitus: MESA",
abstract = "Background—Mechanistic studies suggest that aldosterone impairs glucose metabolism. We investigated the cross-sectional associations of aldosterone and plasma renin activity with fasting plasma glucose, insulin resistance (IR), β-cell function, and longitudinal association with incident diabetes mellitus among adults in MESA (the multiethnic study of atherosclerosis) prospective cohort study. Methods and Results—Homeostatic model assessment of IR (HOMA2-IR) and HOMA2-β were used to estimate IR and β-cell function, respectively. Incident diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dL or anti-diabetic medication use at follow-up. Linear regression was used to examine cross-sectional associations of aldosterone with fasting plasma glucose, HOMA2-IR and HOMA2-β; Cox regression was used to estimate hazard ratios (HR) for incident diabetes mellitus with multivariable adjustment. There were 116 cases of incident diabetes mellitus over 10.5 years among 1570 adults (44{\%} non-Hispanic white, 13{\%} Chinese American, 19{\%} Black, 24{\%} Hispanic American, mean age 64±10 years, 51{\%} female). A 100{\%} increase in log-aldosterone was associated with a 2.6 mg/dL higher fasting plasma glucose, 15{\%} higher HOMA2-IR and 6{\%} higher HOMA2-β (P<0.01). A 1-SD increase in log-aldosterone was associated with a 44{\%} higher risk of incident diabetes mellitus (P<0.01) with the greatest increase of 142{\%} (P<0.01) observed in Chinese Americans (P for interaction=0.09 versus other ethnicities). Similar cross-sectional findings for log-plasma renin activity existed, but log-plasma renin activity was not associated with incident diabetes mellitus after full adjustment. Conclusions—Aldosterone is associated with glucose homeostasis and diabetes mellitus risk with graded associations among Chinese Americans and blacks, suggesting that pleiotropic effects of aldosterone may represent a modifiable mechanism in diabetes mellitus pathogenesis with potential racial/ethnic variation.",
keywords = "Aldosterone, Race and ethnicity, Renin angiotensin system, Type 2 diabetes mellitus",
author = "Joseph, {Joshua J.} and {Echouffo Tcheugui}, Justin and Effoe, {Valery S.} and Hsueh, {Willa A.} and Allison, {Matthew A.} and Golden, {Sherita Hill}",
year = "2018",
month = "9",
day = "1",
doi = "10.1161/JAHA.118.009890",
language = "English (US)",
volume = "7",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "17",

}

TY - JOUR

T1 - Renin-angiotensin-aldosterone system, glucose metabolism and incident type 2 diabetes mellitus

T2 - MESA

AU - Joseph, Joshua J.

AU - Echouffo Tcheugui, Justin

AU - Effoe, Valery S.

AU - Hsueh, Willa A.

AU - Allison, Matthew A.

AU - Golden, Sherita Hill

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background—Mechanistic studies suggest that aldosterone impairs glucose metabolism. We investigated the cross-sectional associations of aldosterone and plasma renin activity with fasting plasma glucose, insulin resistance (IR), β-cell function, and longitudinal association with incident diabetes mellitus among adults in MESA (the multiethnic study of atherosclerosis) prospective cohort study. Methods and Results—Homeostatic model assessment of IR (HOMA2-IR) and HOMA2-β were used to estimate IR and β-cell function, respectively. Incident diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dL or anti-diabetic medication use at follow-up. Linear regression was used to examine cross-sectional associations of aldosterone with fasting plasma glucose, HOMA2-IR and HOMA2-β; Cox regression was used to estimate hazard ratios (HR) for incident diabetes mellitus with multivariable adjustment. There were 116 cases of incident diabetes mellitus over 10.5 years among 1570 adults (44% non-Hispanic white, 13% Chinese American, 19% Black, 24% Hispanic American, mean age 64±10 years, 51% female). A 100% increase in log-aldosterone was associated with a 2.6 mg/dL higher fasting plasma glucose, 15% higher HOMA2-IR and 6% higher HOMA2-β (P<0.01). A 1-SD increase in log-aldosterone was associated with a 44% higher risk of incident diabetes mellitus (P<0.01) with the greatest increase of 142% (P<0.01) observed in Chinese Americans (P for interaction=0.09 versus other ethnicities). Similar cross-sectional findings for log-plasma renin activity existed, but log-plasma renin activity was not associated with incident diabetes mellitus after full adjustment. Conclusions—Aldosterone is associated with glucose homeostasis and diabetes mellitus risk with graded associations among Chinese Americans and blacks, suggesting that pleiotropic effects of aldosterone may represent a modifiable mechanism in diabetes mellitus pathogenesis with potential racial/ethnic variation.

AB - Background—Mechanistic studies suggest that aldosterone impairs glucose metabolism. We investigated the cross-sectional associations of aldosterone and plasma renin activity with fasting plasma glucose, insulin resistance (IR), β-cell function, and longitudinal association with incident diabetes mellitus among adults in MESA (the multiethnic study of atherosclerosis) prospective cohort study. Methods and Results—Homeostatic model assessment of IR (HOMA2-IR) and HOMA2-β were used to estimate IR and β-cell function, respectively. Incident diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dL or anti-diabetic medication use at follow-up. Linear regression was used to examine cross-sectional associations of aldosterone with fasting plasma glucose, HOMA2-IR and HOMA2-β; Cox regression was used to estimate hazard ratios (HR) for incident diabetes mellitus with multivariable adjustment. There were 116 cases of incident diabetes mellitus over 10.5 years among 1570 adults (44% non-Hispanic white, 13% Chinese American, 19% Black, 24% Hispanic American, mean age 64±10 years, 51% female). A 100% increase in log-aldosterone was associated with a 2.6 mg/dL higher fasting plasma glucose, 15% higher HOMA2-IR and 6% higher HOMA2-β (P<0.01). A 1-SD increase in log-aldosterone was associated with a 44% higher risk of incident diabetes mellitus (P<0.01) with the greatest increase of 142% (P<0.01) observed in Chinese Americans (P for interaction=0.09 versus other ethnicities). Similar cross-sectional findings for log-plasma renin activity existed, but log-plasma renin activity was not associated with incident diabetes mellitus after full adjustment. Conclusions—Aldosterone is associated with glucose homeostasis and diabetes mellitus risk with graded associations among Chinese Americans and blacks, suggesting that pleiotropic effects of aldosterone may represent a modifiable mechanism in diabetes mellitus pathogenesis with potential racial/ethnic variation.

KW - Aldosterone

KW - Race and ethnicity

KW - Renin angiotensin system

KW - Type 2 diabetes mellitus

UR - http://www.scopus.com/inward/record.url?scp=85054483418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054483418&partnerID=8YFLogxK

U2 - 10.1161/JAHA.118.009890

DO - 10.1161/JAHA.118.009890

M3 - Article

C2 - 30371168

AN - SCOPUS:85054483418

VL - 7

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 17

M1 - e009890

ER -