Dataset Information

Renal hyperfiltration and arterial stiffness in humans with uncomplicated type 1 diabetes.

ABSTRACT:

Objective

We have reported that renal hyperfiltration is associated with endothelial dysfunction in early type 1 diabetes. However, the relationship between renal hyperfiltration and arterial stiffness is unknown. Accordingly, we measured arterial stiffness in type 1 diabetic subjects with hyperfiltering (n = 20) or normofiltering (n = 18).

Research design and methods

Augmentation index (AIx), aortic pulse wave velocity (PWV), renal hemodynamic function (inulin and paraaminohippurate clearances), and urinary and circulating plasma cGMP were measured in normoalbuminuric subjects with type 1 diabetes during clamped euglycemia (glucose 4-6 mmol/l) and hyperglycemia (glucose 9-11 mmol/l).

Results

During clamped euglycemia, hyperfiltering subjects (glomerular filtration rate >or=135 ml/min/1.73 m(2)) exhibited lower AIx values (-6.1 +/- 2.9 vs. 13.9 +/- 2.7%, P = 0.001) and higher cGMP levels in urine and plasma compared with normofiltering subjects. These differences were maintained during clamped hyperglycemia. As expected, renal hemodynamic responses to clamped hyperglycemia were exaggerated in normofilterers, but values for AIx remained unchanged.

Conclusions

Renal hyperfiltration is associated with reduced arterial stiffness in subjects with uncomplicated type 1 diabetes.

SUBMITTER: Cherney DZ

PROVIDER: S-EPMC2928365 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Publications

Renal hyperfiltration and arterial stiffness in humans with uncomplicated type 1 diabetes.

Cherney David Z I DZ Sochett Etienne B EB Lai Vesta V Dekker Maria G MG Slorach Cameron C Scholey James W JW Bradley Timothy J TJ

Diabetes care 20100628 9

<h4>Objective</h4>We have reported that renal hyperfiltration is associated with endothelial dysfunction in early type 1 diabetes. However, the relationship between renal hyperfiltration and arterial stiffness is unknown. Accordingly, we measured arterial stiffness in type 1 diabetic subjects with hyperfiltering (n = 20) or normofiltering (n = 18).<h4>Research design and methods</h4>Augmentation index (AIx), aortic pulse wave velocity (PWV), renal hemodynamic function (inulin and paraaminohippur ...[more]

PMID: 20585001

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Project description: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.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).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 ± 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.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.NCT01392560.

Dataset Information

Renal hyperfiltration and arterial stiffness in humans with uncomplicated type 1 diabetes.

Objective

Research design and methods

Results

Conclusions

Publications

Renal hyperfiltration and arterial stiffness in humans with uncomplicated type 1 diabetes.

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