Novel Therapies for Metabolic Complications of Lipodystrophies

We propose novel therapeutic approaches for the management of metabolic complications in patients with lipodystrophies. The four interventions to be tested are:

Hypothesis 1: An extremely low fat diet.

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