Key result
Aliskiren (300 mg daily for 30 days) decreased carotid augmentation index (from 26% to 20%, P<0.05) and improved flow-mediated dilation in adults with uncomplicated type 1 diabetes.
Why the study?
Does aliskiren improve renal hemodynamic and systemic vascular function in adults with uncomplicated type 1 diabetes?
Does aliskiren improve renal hemodynamic and systemic vascular function in adults with uncomplicated type 1 diabetes?
Absolute Event Rate: 20% vs 26%
p-value: p=<0.05
Direct renin inhibition with aliskiren exerts renal vasodilatory effects and improves systemic vascular function in adults with uncomplicated type 1 diabetes.
Does not support clinical use of aliskiren in type 1 diabetes; hypothesis-generating and requires randomized confirmation.
OBJECTIVE: Blockade of the renin-angiotensin system (RAS) plays an important role in preventing end-organ injury associated with diabetes. The recent development of direct renin inhibitors (DRIs) provides a new approach to block the RAS, but the effects of DRIs on renal and systemic vascular function in uncomplicated type 1 diabetes have not been elucidated. RESEARCH DESIGN AND METHODS: Renal hemodynamic function (inulin and paraaminohippurate clearance), augmentation index and pulse wave velocity, endothelial dependent vasodilatation (flow-mediated dilation [FMD]), and endothelial independent vasodilatation (response to sublingual nitroglycerin) were evaluated before and after administration of aliskiren (300 mg daily for 30 days) in 10 adult subjects with uncomplicated type 1 diabetes during clamped euglycemia (4-6 mmol/l) and hyperglycemia (9-11 mmol/l). RESULTS: In response to the DRI, plasma renin activity decreased (from 0.40 to 0.13 ng . ml(-1) . h(-1), P < 0.05) and plasma renin increased (from 5.2 to 75.0 ng/l, P < 0.05). Peripheral and central blood pressures decreased, and effective renal plasma flow and glomerular filtration rate increased during clamped euglycemia and hyperglycemia (P < 0.05). The carotid augmentation index during clamped euglycemia decreased (from 26 +/- 6 to 20 +/- 5%, P < 0.05) as did pulse wave velocity during clamped hyperglycemia (from 7.8 +/- 0.6 to 6.8 +/- 0.5 m/s, P < 0.05). In response to the DRI, FMD increased during both clamped euglycemia (from 1.92 +/- 1.13 to 5.55 +/- 0.81%) and hyperglycemia (from 1.86 +/- 0.98 to 5.63 +/- 0.62) as did the vasodilatory response to sublingual nitroglycerin. CONCLUSIONS: DRIs exert a renal vasodilatory effect and improve parameters of systemic vascular function, suggesting that blockade of the RAS with this new class of agents has important functional effects in subjects with uncomplicated type 1 diabetes.
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Cherney et al. (2009) studied Uncomplicated type 1 diabetes (n=10). Aliskiren vs. Baseline (before administration) was evaluated on Carotid augmentation index during clamped euglycemia (p=<0.05). Aliskiren (300 mg daily for 30 days) decreased carotid augmentation index (from 26% to 20%, P<0.05) and improved flow-mediated dilation in adults with uncomplicated type 1 diabetes.
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