Metabolic effects of rosiglitazone in HIV lipodystrophy: a randomized, controlled trial.
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.
Hadigan
Colleen
C
Massachusetts General Hospital and Brigham and Women's Hospital, Boston, Massachusetts 02114, USA. chadigan@partners.org
Yawetz
Sigal
S
Thomas
Abraham
A
Havers
Fiona
F
Sax
Paul E
PE
Grinspoon
Steven
S
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*
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