title: Rosiglitazone in the treatment of HAART-associated lipodystrophy--a randomized double-blind placebo-controlled study.
abstract: Highly active antiretroviral therapy (HAART) is associated with metabolic adverse events such as insulin resistance and lipodystrophy, that is, atrophy of subcutaneous fat and accumulation of intra-abdominal fat. Currently, there is no pharmacological treatment for lipoatrophy. Glitazones, a novel class of insulin-sensitizing anti-diabetic agents, increase subcutaneous fat in patients with type 2 diabetes. There are no controlled studies of glitazones in patients with HAART-associated lipodystrophy (HAL). In this randomized, double-blind, placebo-controlled study, 30 patients with HAL received either rosiglitazone (8 mg daily) or placebo for 24 weeks. Baseline characteristics were compared to a group of 30 age-, sex- and weight-matched HIV-negative controls. At baseline, patients with HAL had 1.8-fold (P<0.001) more intra-abdominal and 2.4-fold (P<0.05) more liver fat than HIV-negative controls, who had 1.8-fold (P<0.001) more subcutaneous fat than the patients. After 24 weeks of treatment, rosiglitazone had no effect on body weight, subcutaneous or intra-abdominal fat (magnetic resonance imaging), total body fat (bioimpedance analysis), anthropometric measurements or serum leptin concentrations (a circulating marker of adipose tissue mass). However, rosiglitazone decreased % liver fat (spectroscopy) and serum insulin concentrations, and normalized liver function tests. During the first 12 weeks of rosiglitazone treatment, serum triglycerides increased from 3.5 +/- 0.5 to 6.5 +/- 2.0 mmol/l (from 310 +/- 44 to 575 +/- 177 mg/dl) (P<0.05) and serum cholesterol from 6.0 +/- 0.4 to 7.8 +/- 0.7 mmol/l (from 232 +/- 15 to 301 +/- 27 mg/dl) (P<0.01). Contrary to data in other patient groups, rosiglitazone did not increase subcutaneous fat in patients with HAL after 24 weeks of treatment. Rosiglitazone seemed to ameliorate insulin resistance judged by the decreased serum insulin concentrations and % liver fat. Rosiglitazone unexpectedly caused significant increases in serum triglyceride and cholesterol concentrations, which must be carefully monitored if glitazones are used in these patients.
authors.affiliation: Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Helsinki, Finland. jussi.sutinen@hus.fi
authors.forename: Jussi
authors.initials: J
authors.lastname: Sutinen
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Häkkinen
authors.forename: Jukka
authors.initials: J
authors.lastname: Westerbacka
authors.forename: Anneli
authors.initials: A
authors.lastname: Seppälä-Lindroos
authors.forename: Satu
authors.initials: S
authors.lastname: Vehkavaara
authors.forename: Juha
authors.initials: J
authors.lastname: Halavaara
authors.forename: Asko
authors.initials: A
authors.lastname: Järvinen
authors.forename: Matti
authors.initials: M
authors.lastname: Ristola
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001823:Body Composition / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D002784:Cholesterol