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Published in:

01-03-2008

Severe Impairment of Endothelial Function with the HIV-1 Protease Inhibitor Indinavir is not Mediated by Insulin Resistance in Healthy Subjects

Authors: Michael P. Dubé, Jude Christopher Gorski, Changyu Shen

Published in: Cardiovascular Toxicology | Issue 1/2008

Abstract

Endothelial dysfunction may contribute to increased cardiovascular events among HIV-1-infected patients receiving antiretroviral therapy. The HIV-1 protease inhibitor indinavir causes both vascular dysfunction and insulin resistance, but the relationship between the two disturbances is not established. Endothelium-dependent vasodilation (EDV), insulin-mediated vasodilation (IMV), and whole body and leg glucose uptake during a euglycemic hyperinsulinemic clamp (40 mU/m²/min) were measured before and after four weeks of indinavir in nine healthy men. EDV fell from 270 ± 67% above basal to 124 ± 30% (P = 0.04) and IMV from 56 ± 14% above basal to 8 ± 8% (P = 0.001) with indinavir. During the clamp, arteriovenous glucose difference and leg glucose uptake were not significantly different after indinavir and whole-body glucose uptake was only modestly reduced (8.0 ± 0.8 vs. 7.2 ± 0.8 mg/kg/min, P = 0.04). The change in EDV did not correlate with the change in whole-body glucose uptake after indinavir (r = 0.21, P = 0.6). Despite marked impairment of endothelial function and IMV with indinavir, only modest, inconsistent reductions in measures of insulin-stimulated glucose uptake occurred. This suggests that indinavir’s effects on glucose metabolism are not directly related to indinavir-associated endothelial dysfunction. Studies of the vascular effects of newer protease inhibitors are needed.

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Title: Severe Impairment of Endothelial Function with the HIV-1 Protease Inhibitor Indinavir is not Mediated by Insulin Resistance in Healthy Subjects
Authors: Michael P. Dubé
Jude Christopher Gorski
Changyu Shen
Publication date: 01-03-2008
Publisher: Humana Press Inc
Published in: Cardiovascular Toxicology / Issue 1/2008
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-007-9010-y

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Severe Impairment of Endothelial Function with the HIV-1 Protease Inhibitor Indinavir is not Mediated by Insulin Resistance in Healthy Subjects

Abstract

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Abstract

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