Severe impairment of endothelial function with the HIV-1 protease inhibitor indinavir is not mediated by insulin resistance in healthy subjects.
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/m(2)/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.
Dubé
Michael P
MP
Department of Medicine and the Division of Infectious Diseases, Indiana University School of Medicine, Wishard Memorial Hospital, 1001 W. 10th Street, Suite OPW-430, Indianapolis, IN 46202, USA. mpdube@iupui.edu
Gorski
Jude Christopher
JC
Shen
Changyu
C
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006801:Humans; D019469:Indinavir / Q000009:adverse effects*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D014664:Vasodilation / Q000187:drug effects
D017320:HIV Protease Inhibitors; D019469:Indinavir; D005947:Glucose