title: Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy.
abstract: BACKGROUND
  Highly active antiretroviral therapy (HAART) for HIV-1 infection has been associated with a metabolic syndrome characterized by insulin resistance, hyperlipidemia, and redistribution of body fat (lipodystrophy). A subset of patients with predominant lipoatrophy has low levels of the adipocyte-secreted hormone leptin.
  
  
  OBJECTIVE
  The objective of the study was to assess whether administration of recombinant methionyl human leptin (r-metHuLeptin) improves insulin resistance and other metabolic abnormalities in HIV+ leptin-deficient subjects with HAART-induced lipoatrophy.
  
  
  METHODS
  We conducted a randomized, placebo-controlled, double-blinded, crossover study from 2002 to 2004 in seven HIV+ men with HAART-induced lipoatrophy, serum leptin level less than 3 ng/ml, and fasting triglyceride level greater than 300 mg/dl, who were administered placebo for 2 months before or after administration of r-metHuLeptin at physiological doses for an additional 2 months.
  
  
  METHODS
  Insulin resistance, lipid levels, inflammatory markers, body composition, and HIV control were measured.
  
  
  RESULTS
  Compared with placebo, r-metHuLeptin therapy improved fasting insulin levels, insulin resistance (as expressed by the homeostasis model assessment index and an insulin suppression test), and high-density lipoprotein. Body weight and fat mass decreased on r-metHuLeptin, mainly due to a decrease in truncal fat but not peripheral fat or lean body mass. r-metHuLeptin was well tolerated, and HIV control was not adversely affected.
  
  
  CONCLUSIONS
  r-metHuLeptin replacement at physiological doses in HIV+ leptin-deficient patients with HAART-induced lipoatrophy improves insulin resistance, high-density lipoprotein, and truncal fat mass. Future larger and more long-term studies in HAART-induced lipoatrophy, including patients with more severe metabolic abnormalities, are warranted to evaluate the physiological and potentially therapeutic role of r-metHuLeptin for this condition and to fully clarify the underlying mechanisms of action.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Stoneman 816, Boston, Massachusetts 02215, USA.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Lee
authors.forename: Jean L
authors.initials: JL
authors.lastname: Chan
authors.forename: Epaminondas
authors.initials: E
authors.lastname: Sourlas
authors.forename: Vassilios
authors.initials: V
authors.lastname: Raptopoulos
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001823:Body Composition; D015992:Body Mass Index; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000378:metabolism; D010919:Placebos; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D008055:Lipids; D008075:Lipoproteins, HDL; D010919:Placebos; D011994:Recombinant Proteins; C122136:recombinant methionyl human leptin