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Aldosterone and myocardial extracellular matrix expansion in type 2 diabetes mellitus.

ABSTRACT: Myocardial extracellular matrix expansion and reduced coronary flow reserve (CFR) occur in patients with type 2 diabetes mellitus without heart failure or coronary artery disease. Because aldosterone is implicated in the pathophysiology of cardiac fibrosis and vascular injury, the aim of this study was to test the hypothesis that aldosterone is associated with extracellular matrix expansion and reduced CFR in type 2 diabetes mellitus. Patients with type 2 diabetes mellitus without evidence of coronary artery disease were recruited. Blood pressure, lipid management, and glycemic control were optimized over 3 months. Cardiac magnetic resonance imaging with T1 mapping was used to measure myocardial extracellular volume (ECV). Cardiac positron emission tomography was used to assess CFR. On a liberal, 250 mEq/day sodium diet, 24-hour urinary aldosterone and change in serum aldosterone with angiotensin II stimulation were measured. Fifty-three participants with type 2 diabetes (68% men, mean age 53 ± 7 years, mean body mass index 32.2 ± 4.3 kg/m², mean glycosylated hemoglobin 6.8 ± 0.7%, mean systolic blood pressure 126 ± 14 mm Hg) without infarction or ischemia by cardiac magnetic resonance and positron emission tomography were studied. Subjects had impaired CFR (2.51 ± 0.83) and elevated ECV (0.36 ± 0.05), despite normal echocardiographic diastolic function and normal left ventricular function. Myocardial ECV, but not CFR, was positively associated with 24-hour urinary aldosterone excretion (r = 0.37, p = 0.01) and angiotensin II-stimulated aldosterone increase (r = 0.35, p = 0.02). In a best-overall multivariate model (including age, gender, body mass index, glycosylated hemoglobin, and blood pressure), 24-hour urinary aldosterone was the strongest predictor of myocardial ECV (p = 0.004). In conclusion, in patients with type 2 diabetes mellitus without coronary artery disease, aldosterone is associated with myocardial extracellular matrix expansion. These results implicate aldosterone in early myocardial remodeling in type 2 diabetes mellitus.

SUBMITTER: Rao AD

PROVIDER: S-EPMC3957437 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Aldosterone and myocardial extracellular matrix expansion in type 2 diabetes mellitus.

Rao Ajay D AD Shah Ravi V RV Garg Rajesh R Abbasi Siddique A SA Neilan Tomas G TG Perlstein Todd S TS Di Carli Marcelo F MF Jerosch-Herold Michael M Kwong Raymond Y RY Adler Gail K GK

The American journal of cardiology 20130415 1

Myocardial extracellular matrix expansion and reduced coronary flow reserve (CFR) occur in patients with type 2 diabetes mellitus without heart failure or coronary artery disease. Because aldosterone is implicated in the pathophysiology of cardiac fibrosis and vascular injury, the aim of this study was to test the hypothesis that aldosterone is associated with extracellular matrix expansion and reduced CFR in type 2 diabetes mellitus. Patients with type 2 diabetes mellitus without evidence of co ...[more]

PMID: 23597770

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Project description: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 ( HOMA 2- IR ) and HOMA 2-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, HOMA 2- IR and HOMA 2-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 HOMA 2- IR and 6% higher HOMA 2-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.

Project description:BACKGROUND:We report relationships between cardiovascular disease risk factors and myocardial structure, function, and scar in patients with type 1 diabetes mellitus in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. METHODS AND RESULTS:Cardiac magnetic resonance was obtained in 1017 patients with type 1 diabetes mellitus. Gadolinium cardiac magnetic resonance was also obtained in 741 patients. The mean age was 49±7 years; 52% were men; and mean duration of diabetes mellitus was 28±5 years. Associations of cardiovascular disease risk factors with cardiac magnetic resonance parameters were examined with linear and logistic regression models. History of macroalbuminuria was positively associated with left ventricular mass (by 14.8 g), leading to a significantly higher ratio of left ventricular mass to end-diastolic volume (by 8%). Mean hemoglobin A(1c) levels over the preceding 22 years were inversely associated with end-diastolic volume (-3.0 mL per unit mean hemoglobin A(1c) percent) and stroke volume (-2.3 mL per unit mean hemoglobin A(1c) percent) and positively related to the ratio of elevated left ventricular mass to end-diastolic volume (0.02 g/mL per unit). The overall prevalence of myocardial scar was 4.3% by cardiac magnetic resonance and 1.4% by clinical adjudication of myocardial infarction. Both mean hemoglobin A(1c) (odds ratio, 1.5 [95% confidence interval, 1.0-2.2] per unit) and macroalbuminuria (odds ratio, 3.5 [95% confidence interval, 1.2-9.9]) were significantly associated with myocardial scar and traditional cardiovascular disease risk factors. CONCLUSIONS:In addition to traditional cardiovascular disease risk factors, elevated mean hemoglobin A(1c) and macroalbuminuria were significantly associated with alterations in left ventricular structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00360893 and NCT00360815.

Project description:AimsAlthough the reno-protective effects of sodium-glucose cotransporter 2 inhibitors are known in patients with heart failure or type 2 diabetes mellitus (T2DM), this effect has not been confirmed in patients with acute myocardial infarction (AMI).Methods and resultsThe prospective, multicentre, randomized, double-blind, placebo-controlled EMBODY trial investigated patients with AMI and T2DM in Japan. The eligible patients included adults aged 20 years or older, diagnosed with AMI and T2DM, and who could be discharged within 2-12 weeks after the onset of AMI. One hundred and five patients were randomized (1:1) to receive once daily 10 mg empagliflozin or placebo within 2 weeks of AMI onset. In this sub-analysis, we investigated the time course of renal functional parameters such as serum creatinine levels and estimated glomerular filtration rate (eGFR) from baseline to Weeks 4, 12, and 24. Ninety-six patients (64 ± 11 years, 78 male) were included in the full analysis (n = 46 and 50 in the empagliflozin and placebo groups, respectively). We used serum creatinine and eGFR as indicators of renal function. In the placebo group, eGFR decreased from 66.14 mL/min/1.73 m2 at baseline to 62.77 mL/min/1.73 m2 by Week 24 (P = 0.023) but remained unchanged in the empagliflozin group (from 64.60 to 64.36 mL/min/1.73 m2 , P = 0.843). In the latter group, uric acid improved from 5.8 mg/dL at baseline to 4.9 mg/dL at Week 24 (P < 0.001). In the earlier analysis of 56 patients with eGFR ≥ 60 mL/min/1.73 m2 , the eGFR decreased and the serum creatinine increased from baseline to 24 weeks in the placebo group, significantly different to the empagliflozin group (-6.61 vs. +0.22 mL/min/1.73 m2 , P = 0.008 and +0.063 vs. -0.001 mg/dL, P = 0.030, respectively). The changes in serum creatinine and eGFR from baseline to Week 24 were significantly correlated with those in uric acid in the placebo group (r = 0.664, P < 0.001 and r = -0.675, P < 0.001, respectively) but not in the empagliflozin group.ConclusionsEmpagliflozin prevented the kidney functional decline in patients with AMI and T2DM, especially those with baseline eGFR ≥ 60 mL/min/1.73 m2 . Early administration of sodium-glucose cotransporter 2 inhibitors in these patients is considered desirable for renal protection.

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Aldosterone and myocardial extracellular matrix expansion in type 2 diabetes mellitus.

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Aldosterone and myocardial extracellular matrix expansion in type 2 diabetes mellitus.

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