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

CONTEXT:

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.

DESIGN, SETTING, PATIENTS, AND INTERVENTION:

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.

MAIN OUTCOME MEASURES:

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: Jennifer H Lee, Jean L Chan, Epaminondas Sourlas, Vassilios Raptopoulos, Christos S Mantzoros
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 91 Issue 7 Pg. 2605-11 (Jul 2006) ISSN: 0021-972X [Print] United States
• PMID: 16636130 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Interleukin-6
• Leptin
• Lipids
• Lipoproteins, HDL
• Placebos
• Recombinant Proteins
• recombinant methionyl human leptin

Topics

• Acquired Immunodeficiency Syndrome (drug therapy)
• Adolescent
• Adult
• Antiretroviral Therapy, Highly Active (adverse effects)
• Body Composition
• Body Mass Index
• Cross-Over Studies
• Double-Blind Method
• HIV-1
• HIV-Associated Lipodystrophy Syndrome (chemically induced, metabolism)
• Humans
• Insulin (blood)
• Insulin Resistance
• Interleukin-6 (blood)
• Leptin (analogs & derivatives, deficiency, therapeutic use)
• Lipids (blood)
• Lipoproteins, HDL (blood)
• Male
• Metabolic Syndrome (chemically induced, metabolism)
• Placebos
• Recombinant Proteins (therapeutic use)