A Pilot Study of Acarbose as Treatment for Pediatric Non-alcoholic Fatty Liver Disease (NAFLD)

The chronic administration of acarbose has been shown to improve insulin resistance and reverse impaired glucose tolerance. Both these conditions, especially insulin resistance, are physiologically associated with the development and progression of NAFLD. Therefore, we hypothesized that the chronic administration of acarbose attenuates NAFLD by improving glucose handling. This would be reflected in a reduction of intrahepatic fat accumulation. Proton Magnetic Resonance Spectroscopy is a sensitive and non-invasive method to measure changes in intrahepatic fat content. The primary endpoint of this study would be to demonstrate a reduction of intrahepatic fat as measured with Proton Magnetic Resonance Spectroscopy after 12 weeks administration of oral acarbose. Other relevant secondary outcomes that have been previously demonstrated to be associated with improvement of NAFLD included improvement of insulin resistance, normalizing of serum adiponectin, and a lowering of serum Leptin.

A second intent of the study is to test the hypothesis of whether the chronic administration of acarbose in patients with NAFLD will influence postprandial substrate metabolism reflected in the RQ measured by indirect calorimetry. The consequence of insulin resistance is a relative inhibition of fatty oxidation. However, the chronic administration of acarbose improves insulin resistance and dampens the post-prandial surge in serum glucose and insulin. These changes in glucose handling could possibly result in a shift towards a pattern of preferential lipid oxidation. We anticipate either a lowering or blunting of the postprandial RQ after chronic administration of acarbose for 3 months.