title: Leptin replacement therapy for the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin on metabolic and hepatic endpoints.
abstract: The clinical manifestations of lipodystrophy syndromes (LS) are hypoleptinemia, hyperglycemia, insulin resistance, dyslipidemia and hepatic steatosis. Leptin replacement therapy (LRT) is effective at improving these pathologies. Currently, there are no data compiling the evidence from the literature, and demonstrating the effect of LRT in LS patients. A systematic review of the MEDLINE and Cochrane Library databases was conducted to identify studies assessing the effect of LRT on metabolic and hepatic endpoints in patients with LS not associated with highly active antiretroviral therapy (HAART) use. Standardized mean differences (SMD) and 95% confidence intervals of pooled results were calculated for overall changes in glucose homeostasis, lipid profile, and hepatic physiology, using an inverse-variance random-effects model. After screening, 12 studies were included for review. Meta-analysis of results from 226 patients showed that LRT decreased fasting glucose [0.75 SMD units (range 0.36-1.13), p=0.0001], HbA1c [0.49 (0.17-0.81), p=0.003], triglycerides [1.00 (0.69-1.31), p<0.00001], total cholesterol [0.62 (0.21-1.02), p=0.003], liver volume [1.06 (0.51-1.61), p=0.0002] and AST [0.41 (0.10-0.73) p=0.01]. In patients with non-HAART LS, LRT improves the outcome of several metabolic and hepatic parameters. Studies were limited by small populations and therefore large prospective trials are needed to validate these findings.
authors.affiliation: Department of Genome Biology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Rodríguez
authors.affiliation: Statistical Consulting Unit, The Australian National University, Canberra, Australia.
authors.forename: Teresa
authors.initials: T
authors.lastname: Neeman
authors.affiliation: Department of Genome Biology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Giles
authors.affiliation: Department of Genome Biology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Mastronardi
authors.affiliation: Department of Genome Biology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Paz Filho
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D020249:Hormone Replacement Therapy; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000172:deficiency / Q000378:metabolism / Q000627:therapeutic use*; D008060:Lipodystrophy / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013577:Syndrome; D000637:Transaminases / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D007328:Insulin; D020738:Leptin; D012709:Serum Albumin; D000637:Transaminases; D014280:Triglycerides; C517652:hemoglobin A1c protein, human