9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 19-21 July 2007, Sydney, Australia

PIOGLITAZONE WITH OR WITHOUT EXERCISE TRAINING REDUCES LIVER LIPID CONTENT AND IMPROVES INSULIN SENSITIVITY IN HIV WITH IMPAIRED GLUCOSE TOLERANCE (IGT)

Antiviral Therapy 2007; 12(Suppl. 2):L14 (abstract no. O-16)

DN Reeds, WT Cade, K Mondy, C Bopp, S Lassa-Claxton and KE Yarasheski
Washington University School of Medicine, St. Louis, MO, USA

AIM: In HIV, pioglitazone improves insulin sensitivity and modestly increases appendicular adipose mass. We hypothesized that pioglitazone and exercise training (PIO+E) would reduce liver lipid content and improve insulin sensitivity more than pioglitazone alone (PIO) in HIV and IGT (ADA criteria).

METHODS: Fourteen HIV+ men and one woman (66% caucasian, 49 ±5 years old, 14 ±6 year HIV+, CD4 641 c/µl, 100% undetectable HIV RNA, 23% body fat and 63% trunk fat) were randomly assigned to receive PIO (30 mg/day, 16 weeks), or PIO+E (resistance and aerobic exercise – 3 days/week, 1.5 h/day; 55–85% maximum capacity). Glucose disposal (GDR) and endogenous glucose production (EGP) rates were measured during a 5-h hyperinsulinaemic (55–65 µU/ml)-euglycaemic (100 mg/dl) clamp with d₂-glucose tracer.

RESULTS: Liver lipid content (1H-MR spectroscopy) declined after PIO (-1.6 ±1.5%) and PIO+E (-7.9 ±3.6%; P=0.08). Trunk and appendicular fat (DEXA) increased with PIO (113 ±570 g and 475 ±207 g, respectively), but decreased with PIO+E (-1,844 ±987 g and -314 ±503 g, respectively). GDR during hyperinsulinaemia improved more (P=0.05) in PIO+E (92% increase over week 0) than PIO (62%). In both groups, baseline fasting EGP was increased (18 ±1 µmol/kg FFM/min), and insulin-induced suppression of EGP improved similarly after treatment (23% versus 31%; P=NS). The improvement in EGP correlated with the reduction in liver lipid content (r²=0.62; P=0.002).

CONCLUSION: Pioglitazone with or without exercise training appears to improve hepatic insulin sensitivity, at least partially by reducing liver lipid content. PIO+E improved peripheral glucose disposal rate and insulin sensitivity more than PIO alone.

Supported by NIH

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2007-07-24
O-16

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