P94 DAPAGLIFLOZIN ACUTELY RESTORES ENDOTHELIAL DYSFUNCTION, REDUCES AORTIC STIFFNESS AND RENAL RESISTIVE INDEX IN TYPE 2 DIABETIC PATIENTS: A PILOT STUDY

Abstract

Objective: Sodium-glucose co-transporter-2 inhibitors reduce blood pressure and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function. Methods: Neuro-hormonal and vascular variables, together with 24h-urinary sodium, glucose, isoprostanes, diuresis and free-water clearance, were assessed before and after a 2- day treatment with dapagliflozin 10 mg/die in 16 type 2 diabetic patients. Brachial artery endothelium-dependent and independent vasodilation (by flow-mediated dilation) and pulse wave velocity were assessed. Renal resistive index was obtained at rest and after glyceril trinitrate administration. Results: Dapagliflozin decreased systolic blood pressure and urinary isoprostanes and induced an increase in 24h-diuresis, 24h-urinary glucose and serum magnesium; 24h-urinary Na and fasting blood glucose were unchanged; serum magnesium slightly increased. Flow-mediated dilation was significantly increased (2.8±2.2 to 4.0±2.1%, p < 0.05), and pulse-wave-velocity was reduced (10.1±1.6 to 8.9±1.6 m/s, p < 0.05), even after correction for mean blood pressure. Renal resistive index was reduced (0.62±0.04 to 0.59±0.05, p < 0.05), as well as its response to nitrates. Conclusions: An acute treatment with Dapagliflozin significantly improves systemic endothelial function, arterial stiffness and renal resistive index; this effect is independent of changes in blood pressure and occurs in the presence of stable natriuresis, suggesting a fast, direct beneficial effect on the vasculature, possibly mediated by oxidative stress reduction.