Primary Outcome Measures:
- Study endpoints will include measurements of insulin sensitivity, hepatic insulin clearance, and altered parameters of lipid metabolism, changes in the histological features that define NAFLD, and quantitative measurements of visceral and peripheral fat. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Tests the postulate that metformin will improve insulin sensitivity in NAFLD. Also test the postulate that improving IR with an insulin sensitizing agent will improve biochemical and histological features of NAFLD. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Determine if metformin improves the altered parameters of lipid metabolism as compared to placebo. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Measure the differential effects of IR and lipid metabolism on peripheral mononuclear cell (PBMC) inflammatory response and the associated hepatocyte mitochondrial ultrastructure and measures of oxidative stress [ Time Frame: 24 months ] [ Designated as safety issue: No ]
NAFLD is a poorly understood disease which may cause an enlarged liver, abnormal liver test results, and scarring of the liver. It may occur more often in people with obesity, high levels of cholesterol (blood fats), diabetes (high blood sugar), or the insulin resistance syndrome (where a person's body does not respond to the hormone insulin which helps keep blood sugar levels normal). Currently, no effective drug treatment for NAFLD exists. There is increasing evidence that NAFLD may be a condition due to a problem with metabolism (the way your body uses energy). Previous studies have shown that high glucose (sugar) levels may play an important role in the development of fatty liver disease. Medications that decrease your natural glucose level may reduce the amount of fat in the liver and, therefore, might be useful in the treatment of NAFLD. Metformin, a drug approved by the U.S. Food and Drug Administration (FDA) for use in patients with diabetes, has been shown to improve fatty liver in animals and in a small number of human beings.