Background:  PPARg agonists, such as rosiglitazone, are novel antidiabetic drugs. Rosiglitazone increases subcutaneous fat in type-2 diabetic patients. It also reverses the block in adipose tissue differentiation induced by HAART in vitro. We studied whether rosiglitazone reverses HAL.

 

Methods:  30 patients with HAL were randomized to receive either 8 mg rosiglitazone or placebo for 24 weeks. Visceral fat and abdominal subcutaneous fat (s.c.) were measured using MRI. Liver fat was determined by proton spectroscopy. Leptin, which is synthesized exclusively in adipose tissue and correlates closely with body fat mass was determined as an additional measure of fat mass. Serum concentrations of lipids, insulin, and liver enzymes were also determined.

 

Results:  There were no statistically significant differences between the groups at baseline.

 

Parameter	Rosiglitazone (n=15) Baseline                24 weeks	Placebo (n=15) Baseline               24 weeks
Age (years) Body mass index (kg/m2) S.c fat (cm3) Visceral fat (cm3) Waist to hip ratio Serum leptin (ng/mL)   Serum insulin (mU/L) Serum triglycerides (mmol/L) Serum cholesterol (mmol/L)     S-ALT (U/L) Liver fat (%)	44±3 23.7±0.7               23.9±0.6 78±12                   80±15 143±20                 143±19 0.98±0.02             0.98±0.02 4.2±1.0                 3.8±0.9   13±2                     9±1* 3.5±0.5                 4.7±0.9* 6.0±0.4                 7.2±0.6*   46±7                     32±4* 7.3±1.6                 6.2±1.3*	42±2 23.6±0.8               23.9±0.9 104±18                 102±16 139±22                 142±27 0.99±0.02             0.99±0.02 3.8±0.8                 3.9±0.9   10±2                     16±6* 3.2±0.5                 3.8±1.0* 5.9±0.2                 5.9±0.3*   45±6                     42±5* 8.0±3.1                 10.1±3.3*

 

*p <0.05 for change by treatment between the rosiglitazone and placebo groups. Data are mean  ± SEM.

 

Conclusions:  Rosiglitazone ameliorates insulin resistance as determined from the decrease in serum insulin  concentrations. However, in contrast to type-2 diabetic patients, rosiglitazone induces a clear increase in serum triglycerides and does not increase subcutaneous fat as determined by MRI or serum leptin levels. These data demonstrate that HAL is not reversible with rosiglitazone treatment.