title: Metabolic effects of rosiglitazone in HIV lipodystrophy: a randomized, controlled trial.
abstract: BACKGROUND
  Patients with HIV infection who are treated with antiretroviral agents often lose subcutaneous fat and have metabolic abnormalities, including insulin resistance and reduced adiponectin levels, which may be related to disrupted subcutaneous adipogenesis and altered peroxisome proliferator-activated receptor-gamma signaling.
  
  
  OBJECTIVE
  To investigate the effects of rosiglitazone (4 mg/d), a peroxisome proliferator-activated receptor-gamma agonist, in HIV-infected men and women with hyperinsulinemia and lipoatrophy.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, 3-month study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  28 HIV-infected men and women with hyperinsulinemia and lipoatrophy.
  
  
  METHODS
  Insulin sensitivity measured by euglycemic hyperinsulinemic clamp testing; subcutaneous leg fat area measured by computed tomography; adiponectin, free fatty acid, and lipid levels; and safety variables.
  
  
  RESULTS
  Rosiglitazone, when compared with placebo, improved insulin sensitivity (mean [+/-SD] change, 1.5 +/- 2.1 mg of glucose/kg of lean body mass per minute vs. -0.4 +/- 1.6 mg/kg per minute; P = 0.02), increased adiponectin levels (mean [+/-SD], 2.2 +/- 2.2 micro g/mL vs. 0.1 +/- 1.1 microg/mL; P = 0.006), and reduced free fatty acid levels (mean [+/-SD], -0.09 +/- 0.1 mmol/L vs. 0.01 +/- 0.1 mmol/L; P = 0.02). Mean percentage (+/-SD) of body fat (1.38% +/- 3.03% vs. -0.83% +/- 2.76%; P = 0.03) and subcutaneous leg fat area (2.3 +/- 8.4 cm2 vs. -0.9 +/- 1.9 cm2; P = 0.02) increased significantly with rosiglitazone compared with placebo. Mean total cholesterol levels (+/-SD) also increased with rosiglitazone compared with placebo (0.6 +/- 1.0 mmol/L [25 +/- 37 mg/dL] vs. -0.4 +/- 0.6 mmol/L [-15 +/- 25 mg/dL]; P = 0.007).
  
  
  CONCLUSIONS
  The study was relatively small and of short duration.
  
  
  CONCLUSIONS
  The authors demonstrated positive effects of rosiglitazone on lipoatrophy; insulin sensitivity; and metabolic indices, including adiponectin levels, in HIV-infected patients with lipoatrophy and insulin resistance. Peroxisome proliferator-activated receptor-gamma agonists may correct the metabolic abnormalities associated with disrupted adipogenesis in this population. Further studies must determine the clinical utility of such agents in HIV-infected patients.
authors.affiliation: Massachusetts General Hospital and Brigham and Women's Hospital, Boston, Massachusetts 02114, USA. chadigan@partners.org
authors.forename: Colleen
authors.initials: C
authors.lastname: Hadigan
authors.forename: Sigal
authors.initials: S
authors.lastname: Yawetz
authors.forename: Abraham
authors.initials: A
authors.lastname: Thomas
authors.forename: Fiona
authors.initials: F
authors.lastname: Havers
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Steven
authors.initials: S
authors.lastname: Grinspoon
mesh_terms: D052242:Adiponectin; D000328:Adult; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D039682:HIV-Associated Lipodystrophy Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014157:Transcription Factors / Q000819:agonists*
chemical_list: D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone