| The endothelin receptor antagonist bosentan improves peripheral endothelial function in patients with type 2 diabetes mellitus and microalbuminuria: a randomised trial. | |
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MedLine Citation:
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PMID: 22200728 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: Endothelial dysfunction is important in the development of vascular complications in diabetes. Patients with type 2 diabetes have increased production of the vasoconstrictor and pro-inflammatory peptide, endothelin-1. Short-term intra-arterial administration of endothelin antagonists improves endothelium-dependent vasodilatation in patients with type 2 diabetes. We tested the hypothesis that oral administration of the dual endothelin receptor antagonist, bosentan, improves peripheral endothelial function in patients with type 2 diabetes and microalbuminuria. METHODS: This placebo-controlled and double-blind study was performed on 46 patients with type 2 diabetes and microalbuminuria (urine albumin/creatinine ratio >3 mg/mmol) at a medical university department. Patients were randomised to bosentan, 125 mg two times per day (n = 28), or placebo (n = 28) for 4 weeks. The computer-generated randomisation code was kept in sealed envelopes. Patients and people doing examinations or assessing outcomes were blinded. The primary endpoint was change in microvascular endothelium-dependent vasodilatation, based on change in digital reactive hyperaemia index. The secondary endpoint was change in brachial artery flow-mediated vasodilatation. RESULTS: Reactive hyperaemia index increased from 1.73 ± 0.43 (mean ± SD) at baseline to 2.08 ± 0.59 at follow-up (p < 0.05) in the bosentan group (n = 22), but did not change in the placebo group (1.84 ± 0.49 to 1.87 ± 0.47; n = 24). The change in reactive hyperaemia index from baseline was greater in the bosentan group than in the placebo group (p < 0.05). Nitroglycerine-induced digital hyperaemia was not affected. Brachial artery flow-mediated vasodilatation and blood pressure did not change during treatment. CONCLUSIONS/INTERPRETATION: Oral treatment of 4 weeks duration with the dual endothelin receptor antagonist, bosentan, improves peripheral endothelial function in patients with type 2 diabetes and microalbuminuria. TRIAL REGISTRATION: ClinicalTrial.gov NCT01357109; Karolinska Clinical Trial Registration Identifier CT20090017 (see www.kctr.se ) FUNDING: Research Council of Sweden, Swedish Heart and Lung Foundation, Novo Nordisk Foundation, Karolinska Institutet/Stockholm County Council Strategic Cardiovascular Programme, Gustav V and Queen Victoria Foundation, the Family Erling Persson Foundation, Actelion Pharmaceuticals and Actelion Research Award. |
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Authors:
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A Rafnsson; F Böhm; M Settergren; A Gonon; K Brismar; J Pernow |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-27 |
Journal Detail:
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Title: Diabetologia Volume: - ISSN: 1432-0428 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Karolinska Institutet, Department of Medicine, Cardiology Unit, Karolinska University Hospital, Solna, 171 76, Stockholm, Sweden, arnar.rafnsson@karolinska.se. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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