Indinavir impairs endothelial function without insulin resistance
Graham McKerrow, HIV i-Base
Treatment for 4 weeks with indinavir (IDV, Crixivan) monotherapy markedly impairs endothelial function and insulin-mediated vasodilation, without significant impairment of whole-body glucose disposal, according to an American study. So it appears unlikely that insulin resistance plays a major role in the induction of endothelial dysfunction.
Dubé and colleagues hypothesised that IDV-induced endothelial dysfunction occurred because of IDV-induced insulin resistance. Their study assessed insulin sensitivity, endothelial function, and insulin-mediated vasodilation in 16 lean, healthy, male subjects before and after 4 weeks of IDV 800mg TID.
Subjects were 37+/-3 years old, with BMI of 25+/-1 kg/m2, body fat of 19.6+/-1.9%, total cholesterol: 171+/-8 mg/dL; LDL-cholesterol: 98+/-7 mg/dl; HDL-cholesterol: 50+/-4 mg/dl; triglycerides: 140+/-39 mg/dl, and resting leg blood flow (LBF) of 0.207+/-0.015 l/min. There was no significant change in any of these parameters after IDV. Plasma adiponectin levels increased after IDV (16.4+/-2.2 ug/ml pre-IDV, 19.1+/-2.3 ug/ml post-IDV, p<0.05). Normal, robust endothelium-dependent and insulin-mediated vasodilatory responses were present at baseline. After IDV, there was a marked blunting of endothelium-dependent vasodilation (258+/-43% pre-IDV vs 60+/-13% post, p<0.05) and insulin-mediated vasodilation (70+/-10% pre-IDV vs 16+/-6% post, p<0.05). In spite of these dramatic effects on vascular function, there was no significant change in the steady-state whole body glucose-disposal rate with IDV (8.0+/-0.6 mg/kg/min pre-IDV vs 7.5+/-0.6 post, p=NS).
Dubé MP, Shankar SS, Considine RV et al. Marked impairment of endothelial function without insulin resistance in healthy men treated with the HIV-1 protease inhibitor indinavir. 6th Lipodystrophy Workshop (6th IWADRLH), Washington, 2004. Abstract 95. Antiviral Therapy 2004; 9:L55.