The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus

Cardiovascular Diabetology

Original Investigation

Nima Soleymanlou¹  Uli C Broedl²  Hans-Juergen Woerle²  Odd Erik Johansen²  Nora Fagan³  Maximilian von Eynatten³  Bruce A Perkins⁴  Ronnie Har⁵  David ZI Cherney⁵ 

[1] Boehringer Ingelheim Canada Ltd./Ltée, Burlington, Canada;Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim, Germany;Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA;Division of Endocrinology, University Health Network, University of Toronto, Toronto, Canada;Division of Nephrology, University Health Network, University of Toronto, Toronto General Hospital, 585 University Ave, Toronto 8N-845, M5G 2N2, Ontario, Canada;

关键词: Diabetes mellitus;    Systemic blood pressure;    SGLT2 inhibition;    Empagliflozin;    Hyperglycaemia;    Arterial stiffness;    Heart rate variability;   

DOI  :  10.1186/1475-2840-13-28

 received in 2013-11-18, accepted in 2014-01-23,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundIndividuals with type 1 diabetes mellitus are at high risk for the development of hypertension, contributing to cardiovascular complications. Hyperglycaemia-mediated neurohormonal activation increases arterial stiffness, and is an important contributing factor for hypertension. Since the sodium glucose cotransport-2 (SGLT2) inhibitor empagliflozin lowers blood pressure and HbA1c in type 1 diabetes mellitus, we hypothesized that this agent would also reduce arterial stiffness and markers of sympathetic nervous system activity.MethodsBlood pressure, arterial stiffness, heart rate variability (HRV) and circulating adrenergic mediators were measured during clamped euglycaemia (blood glucose 4–6 mmol/L) and hyperglycaemia (blood glucose 9–11 mmol/L) in 40 normotensive type 1 diabetes mellitus patients. Studies were repeated after 8 weeks of empagliflozin (25 mg once daily).ResultsIn response to empagliflozin during clamped euglycaemia, systolic blood pressure (111 ± 9 to 109 ± 9 mmHg, p = 0.02) and augmentation indices at the radial (-52% ± 16 to -57% ± 17, p = 0.0001), carotid (+1.3 ± 1 7.0 to -5.7 ± 17.0%, p < 0.0001) and aortic positions (+0.1 ± 13.4 to -6.2 ± 14.3%, p < 0.0001) declined. Similar effects on arterial stiffness were observed during clamped hyperglycaemia without changing blood pressure under this condition. Carotid-radial pulse wave velocity decreased significantly under both glycemic conditions (p ≤ 0.0001), while declines in carotid-femoral pulse wave velocity were only significant during clamped hyperglycaemia (5.7 ± 1.1 to 5.2 ± 0.9 m/s, p = 0.0017). HRV, plasma noradrenalin and adrenaline remained unchanged under both clamped euglycemic and hyperglycemic conditions.ConclusionsEmpagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects. The underlying mechanisms may relate to pleiotropic actions of SGLT2 inhibition, including glucose lowering, antihypertensive and weight reduction effects.Trial registrationClinical trial registration: NCT01392560

【 授权许可】

CC BY   
© Cherney et al.; licensee BioMed Central Ltd. 2014