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Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study.

Authors
 Faidon Magkos ; Aoife Brennan ; Christos S. Mantzoros ; Adolf W. Karchmer ; John Doweiko ; Eun Seok Kang ; Laura Sweeney 
Citation
 Metabolism-Clinical and Experimental, Vol.60(7) : 1045~1049, 2011 
Journal Title
 Metabolism-Clinical and Experimental 
ISSN
 0026-0495 
Issue Date
2011
Abstract
Highly active antiretroviral therapy (HAART)-induced lipoatrophy is characterized by hypoleptinemia and insulin resistance. Evidence suggests that pioglitazone and recombinant methionyl human leptin (metreleptin) administration has beneficial effects in human immunodeficiency virus (HIV)-infected lipoatrophic patients. This proof-of-concept study aimed at evaluating whether the combination of metreleptin and pioglitazone has favorable effects, above and beyond pioglitazone alone, on both metabolic outcomes and peripheral lipoatrophy in HIV-infected patients on HAART. Nine HIV-positive men with at least 6 months of HAART exposure, clinical evidence of lipoatrophy, and low leptin concentrations (≤4 ng/mL) were placed on pioglitazone treatment (30 mg/d per os) and were randomized to receive either metreleptin (0.04 mg/kg subcutaneously once daily; n = 5) or placebo (n = 4) for 3 months in a double-blinded fashion. Compared with placebo, metreleptin reduced fasting serum insulin concentration, increased adiponectin concentration, reduced the homeostasis model assessment index of insulin resistance, and attenuated postprandial glycemia in response to a mixed meal (all P ≤ .02), but did not affect trunk and peripheral fat mass. HIV control was not affected, and no major adverse effects were observed. Metreleptin administration in HIV-positive, leptin-deficient patients with lipoatrophy treated with pioglitazone improves postprandial glycemia and insulin sensitivity. Results from this pilot study should be confirmed in larger clinical trials.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/94041
DOI
10.1016/j.metabol.2010.10.002
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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