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

被引:413
作者
Cherney, David Z. I. [1 ]
Perkins, Bruce A. [2 ]
Soleymanlou, Nima [3 ]
Har, Ronnie [1 ]
Fagan, Nora [4 ]
Johansen, Odd Erik [5 ]
Woerle, Hans-Juergen [5 ]
von Eynatten, Maximilian [4 ]
Broedl, Uli C.
机构
[1] Univ Toronto, Univ Hlth Network, Toronto Gen Hosp, Div Nephrol, Toronto, ON M5G 2N2, Canada
[2] Univ Toronto, Univ Hlth Network, Div Endocrinol, Toronto, ON M5G 2N2, Canada
[3] Boehringer Ingelheim Canada Ltd Ltee, Burlington, ON, Canada
[4] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT USA
[5] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany
关键词
Diabetes mellitus; Systemic blood pressure; SGLT2; inhibition; Empagliflozin; Hyperglycaemia; Arterial stiffness; Heart rate variability; GLOMERULAR-FILTRATION-RATE; INTENSIVE GLYCEMIC CONTROL; BLOOD-PRESSURE; ENDOTHELIAL FUNCTION; DOUBLE-BLIND; WEIGHT-LOSS; ADD-ON; SGLT2; INHIBITORS; IMPROVES; METFORMIN;
D O I
10.1186/1475-2840-13-28
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Individuals 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. Methods: Blood 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). Results: In 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 +/- 17.0 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. Conclusions: Empagliflozin 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.
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页数:8
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