Novel Therapies for Metabolic Complications of Lipodystrophies

Inclusion Criteria: General Inclusion criteria: * Patients with lipodystrophies as diagnosed by clinical criteria * Any one of the following: * Diabetes mellitus, or * Fasting serum triglycerides greater than 200 mg/dL, or * Fasting serum insulin greater than 30 U/mL, or * Hepatic steatosis ( greater than 5.6% hepatic triglyceride content) as demonstrated by 1H MRS. Exclusion Criteria: * Known liver disease due to causes other than non-alcoholic steatohepatitis: * Current alcohol abuse (more than 7 drinks or 210 g per wk for women and more than 14 drinks or 420 g per wk for men). * Positive serological markers of hepatitis B and C. * Autoimmune hepatitis, autoimmune cholestatic liver disorders, Wilson disease and Alpha-1-antitrypsin deficiency as indicated by clinical and laboratory tests. * Drug-induced liver disease * Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study suggestive of liver cancer. * Decompensated liver disease as evidenced by clinical features of hepatic failure (variceal bleeding, ascites, hepatic encephalopathy etc.) and laboratory investigations (prolonged prothrombin time, hypoalbuminemia, presence of esophageal varices etc.) * Use of the drugs which can potentially decrease hepatic steatosis during previous 3 months; high-dose vitamin E, betaine, acetylcysteine, choline and probucol. * Significant systemic or major illnesses other than liver disease (congestive heart failure, unstable angina, cerebrovascular disease, respiratory failure, renal failure \[serum creatinine more then 2 mg/dL\], acute pancreatitis, organ transplantation, serious psychiatric disease, and malignancy) that could interfere with the trial and adequate follow up. * Acute medical illnesses precluding participation in the studies. * Known HIV infected patient. * Current substance abuse. * Pregnant or lactating women. * Hematocrit of less than 30%. * History of weight loss ( more than 10%) or use of weight loss drugs such as sibutramine or orlistat in the last 3 months. Each subproject has additional specific inclusion and exclusion criteria