BACKGROUND: Therapy with some HIV protease inhibitors (PI) contributes to insulin resistance and type 2 diabetes mellitus, by inhibition of insulin-sensitive glucose transporters. Atazanavir (ATV) is a new PI with substantially less in vitro effect on glucose transport than observed with other PI, including lopinavir (LPV) or ritonavir (RTV). METHODS: Randomized, double-blind, crossover study of the effect of 5 days of administering ATV, lopinavir/ritonavir (LPV/r) or placebo on insulin-stimulated glucose disposal in 30 healthy HIV-negative subjects. Each subject was studied on two of three possible treatments with a wash-out period between treatments. RESULTS: The mean insulin-stimulated glucose disposal (mg/min per kg body weight) per unit insulin (microU/ml) (M/I) was 9.88, 9.80 and 7.52 for placebo, ATV and LPV/r, respectively (SEM, 0.84 for all). There was no significant difference between ATV and placebo. The M/I for LPV/r was 23% lower than that for ATV (P = 0.010) and 24% lower than that for placebo (P = 0.008). The mean glycogen storage rates were 3.85, 4.00 and 2.54 mg/min per kg for placebo, ATV and LPV/r, respectively (SEM, 0.39 for all). There was no significant difference between ATV and placebo. The glycogen storage rate for LPV/r was 36% lower than ATV (P = 0.003) and 34% lower than placebo (P = 0.006). CONCLUSIONS:ATV given to healthy subjects for 5 days did not affect insulin sensitivity, while LPV/r induced insulin resistance. This observation is consistent with differential in vitro effects of these PI on glucose transport. Further data are needed to assess clinical implications for body composition.
RCT Entities:
BACKGROUND: Therapy with some HIV protease inhibitors (PI) contributes to insulin resistance and type 2 diabetes mellitus, by inhibition of insulin-sensitive glucose transporters. Atazanavir (ATV) is a new PI with substantially less in vitro effect on glucose transport than observed with other PI, including lopinavir (LPV) or ritonavir (RTV). METHODS: Randomized, double-blind, crossover study of the effect of 5 days of administering ATV, lopinavir/ritonavir (LPV/r) or placebo on insulin-stimulated glucose disposal in 30 healthy HIV-negative subjects. Each subject was studied on two of three possible treatments with a wash-out period between treatments. RESULTS: The mean insulin-stimulated glucose disposal (mg/min per kg body weight) per unit insulin (microU/ml) (M/I) was 9.88, 9.80 and 7.52 for placebo, ATV and LPV/r, respectively (SEM, 0.84 for all). There was no significant difference between ATV and placebo. The M/I for LPV/r was 23% lower than that for ATV (P = 0.010) and 24% lower than that for placebo (P = 0.008). The mean glycogen storage rates were 3.85, 4.00 and 2.54 mg/min per kg for placebo, ATV and LPV/r, respectively (SEM, 0.39 for all). There was no significant difference between ATV and placebo. The glycogen storage rate for LPV/r was 36% lower than ATV (P = 0.003) and 34% lower than placebo (P = 0.006). CONCLUSIONS:ATV given to healthy subjects for 5 days did not affect insulin sensitivity, while LPV/r induced insulin resistance. This observation is consistent with differential in vitro effects of these PI on glucose transport. Further data are needed to assess clinical implications for body composition.
Authors: Carl Grunfeld; Donald P Kotler; Donna K Arnett; Julian M Falutz; Steven M Haffner; Paul Hruz; Henry Masur; James B Meigs; Kathleen Mulligan; Peter Reiss; Katherine Samaras Journal: Circulation Date: 2008-06-19 Impact factor: 29.690
Authors: Oliver P Flint; Mustafa A Noor; Paul W Hruz; Phil B Hylemon; Kevin Yarasheski; Donald P Kotler; Rex A Parker; Aouatef Bellamine Journal: Toxicol Pathol Date: 2009-01-26 Impact factor: 1.902
Authors: Edward P Acosta; Michelle A Kendall; John G Gerber; Beverly Alston-Smith; Susan L Koletar; Andrew R Zolopa; Sangeeta Agarwala; Michael Child; Richard Bertz; Lara Hosey; David W Haas Journal: Antimicrob Agents Chemother Date: 2007-06-18 Impact factor: 5.191