Abstract
BackgroundWe recently found that overexpression of angiotensin (Ang)-converting enzyme 2, which metabolizes Ang-II to Ang-(1–7) and Ang-I to Ang-(1–9), may prevent diabetes-induced left ventricular remodeling and dysfunction in rats. Our objective was to evaluate the association of plasma Ang-(1–7) level and left ventricular function in patients with type 2 diabetes mellitus.Methodology/Principal FindingsWe measured the left ventricular ejection fraction (EF), ratio of early to late left ventricular filling velocity (E/A) and ratio of early diastolic mitral inflow to annular velocity (E/Ea) by ultrasonography in 110 patients with type 2 diabetes mellitus for more than 5 years. Anthropometric and fasting blood values were obtained from medical records. The plasma Ang-(1-7) level in patients with a poor EF (<50%) was significantly lower than that in patients with EF ≥50%; the level in patients with E/A <1 was significantly lower than that in patients with E/A ≥1; and the level in patients with E/Ea >15 was significantly lower than that in patients with E/Ea ≤15. Ang-(1–7) level was negatively correlated with E/Ea and Log-N-terminal pro-B-type natriuretic peptide and positively with EF and E/A. Stepwise multiple regression analysis revealed that Ang-(1–7), hemoglobin A1c and Ang-II levels as well as duration of diabetes predicted EF; Ang-(1–7) level, fasting blood glucose, low-density lipoprotein cholesterol level and duration of diabetes predicted E/A; and Ang-(1–7) and hemoglobin A1c levels predicted E/Ea.Conclusions/SignificancePlasma Ang-(1–7) level is independently associated with left ventricular function in patients with type 2 diabetes mellitus and may be a biomarker for assessing cardiac function in such patients.
Highlights
The incidence of type 2 diabetes mellitus has been increasing worldwide and rapidly assuming epidemic proportions over the last several decades
The role of this system in cardiac remodeling is exemplified by Ang-converting enzyme (ACE) inhibitors and Ang-II type 1 receptor (AT1) blockers, which improve survival in patients with heart failure, slowing down and in some cases even reversing the deregulation of certain variables of cardiac remodeling [6]
Our results reveal a high burden of left ventricular (LV) systolic and diastolic dysfunction in patients with type 2 diabetes mellitus and show that plasma Ang-(1–7) level was negatively and significantly associated with E/Ea and Log-NT-proBNP and positively with ejection fraction (EF) and E/A in diabetic patients
Summary
The incidence of type 2 diabetes mellitus has been increasing worldwide and rapidly assuming epidemic proportions over the last several decades. The mechanisms leading to diabetes-induced cardiac remodeling and dysfunction are not completely understood but are thought to arise from a common upstream pathway involving the renin–angiotensin (Ang) system (RAS) The role of this system in cardiac remodeling is exemplified by Ang-converting enzyme (ACE) inhibitors and Ang-II type 1 receptor (AT1) blockers, which improve survival in patients with heart failure, slowing down and in some cases even reversing the deregulation of certain variables of cardiac remodeling [6]. Many other mechanisms, such as microvascular disease, autonomic dysfunction, metabolic disorders, and interstitial fibrosis, may cause diabetic cardiomyopathy [7]. Our objective was to evaluate the association of plasma Ang-(1–7) level and left ventricular function in patients with type 2 diabetes mellitus
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