4324Effects of the glucagon like peptide-1 receptor agonist on arterial stiffness, LV myocardial deformation and oxidative stress in newly diagnosed type 2 diabetes after 6-month treatment

Abstract

Aim: Agonists of Glucagon like peptide-1 receptors (GLP-1R) are used in the treatment of type 2 diabetes mellitus (T2DM). We investigated whether changes in arterial stiffness and LV myocardial deformation are linked with changes in oxidative stress after 6-month treatment with GLP-1R agonist. Methods: We examined 60 patients with newly diagnosed and never treated type 2 diabetes. Thirty subjects were randomized to receive the GLP-1R agonist liraglutide, and 30 subjects received metformin for 6 months. We measured at baseline and after 6-months of treatment a) carotid-femoral pulse wave velocity (PWV - Complior SP ALAM), central systolic blood pressure (cSBP) and augmentation index (AI) b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. The degree of LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw - UtwMVO), at peak (%dpTw-UtwPEF) and end of early LV diastolic filling (%dpTw-UtwEDF) c) Flow mediated dilatation (FMD) of the brachial artery and percentage difference of FMD (FMD%) after hyperemia d) malondialdehyde (MDA) and protein carbonyls (PCs) plasma levels. Results: After six-month treatment, subjects who received GLP-1RA achieved a reduction of PWV (11.8±2.5 vs. 10.3±3.3 m/sec) and MDA (1.47±0.2 vs. 0.89±0.2 nM/L) in parallel with an increase of GLS (-15.4±3 vs. -16.6±2.7, Fig. 1), pUtwVel (-97±49 vs. -112±52 deg), %dpTw-UtwMVO (31±10 vs. 40±14), %dpTw-UtwPEF (43±19 vs. 53±22) and FMD% (8.9±3 vs. 13.2±6), (p<0.05 for all comparisons). There were no statistically significant differences in subjects that received metformin. At baseline, reduced GLS was related with elevated HbA1c (r=0.39), PWV (r=0.47) and reduced FMD% (r=-0.29). In addition, GLSR was inversely related with HbA1c (r=-0.35) and PWV (r=-0.50) while cSBP was associated with %dpTw - UtwMVO (r=0.29) (p<0.05 for all associations) In all subjects, PCs levels at baseline were negatively related with the difference of GLS (r=-0.53) post treatment and the difference of MDA was associated with the difference of PWV (r=0.52) (p<0.05 for all associations) after 6-month treatment. (Figure presented).