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Improved insulin sensitivity with the angiotensin II-receptor blocker losartan in patients with hypertension and other cardiovascular risk factors

Abstract

We aimed to compare the effects of two different vasodilating principles, angiotensin II-receptor blockade and calcium channel blockade, on peripheral insulin-mediated glucose uptake in patients with hypertension and other cardiovascular risk factors. Twenty-one hypertensive patients (11 women and 10 men) with mean age 58.6 years (range 46–75 years), body mass index 29.2±1.0 kg/m2 and blood pressure 160±3/96±2 mm Hg entered a 4-week run-in period with open-label amlodipine 5 mg. Thereafter they were randomized double-blindly to additional treatment with amlodipine 5 mg or losartan 100 mg. After 8 weeks of treatment, all patients underwent clinical examination and laboratory testing, and 17 of them underwent a hyperinsulinaemic isoglycaemic glucose clamp. After a 4-week open-label wash-out phase, the participants crossed over to the opposite treatment regimen and final examinations with hyperinsulinaemic isoglycaemic glucose clamp after another 8 weeks. Blood pressure was lowered to the same level in both treatment periods. The glucose disposal rate was significantly higher after treatment with losartan 100 mg+amlodipine 5 mg compared to amlodipine 10 mg (4.9±0.4 vs 4.2±0.5 mg/kg/min, P=0.039). Thus our data suggest that angiotensin II-receptor blockade with losartan improves glucose metabolism at the cellular level beyond what can be expected by the vasodilatation and blood pressure reduction alone.

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Acknowledgements

We thank biochemist Roseli Andreassen for technical assistance and the Department of Clinical Chemistry at Ullevaal University Hospital and Dr Knut Lande for analyzing glucose, HbA1c, lipids and uric acid. We also thank Merck & Co., USA for school grant support. We are indebted to physicians and staff at Bentsebro legesenter, Collosseumklinikken, Ekeberg legesenter, L11 Familiehelsesenter, Manglerud legekontor, Nordseter legekontor, Nordstrand legekontor and Trosterud legekontor in Oslo for their kind help with recruiting patients.

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Aksnes, T., Reims, H., Guptha, S. et al. Improved insulin sensitivity with the angiotensin II-receptor blocker losartan in patients with hypertension and other cardiovascular risk factors. J Hum Hypertens 20, 860–866 (2006). https://doi.org/10.1038/sj.jhh.1002087

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