Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study
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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. / Magkos, Faidon; Brennan, Aoife; Sweeney, Laura; Kang, Eun Seok; Doweiko, John; Karchmer, Adolf W; Mantzoros, Christos S.
I: Metabolism, Bind 60, Nr. 7, 2011, s. 1045-1049.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study
AU - Magkos, Faidon
AU - Brennan, Aoife
AU - Sweeney, Laura
AU - Kang, Eun Seok
AU - Doweiko, John
AU - Karchmer, Adolf W
AU - Mantzoros, Christos S
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Adiponectin/blood
KW - Adult
KW - Antiretroviral Therapy, Highly Active/adverse effects
KW - Blood Glucose
KW - Body Mass Index
KW - Drug Therapy, Combination
KW - HIV-1
KW - HIV-Associated Lipodystrophy Syndrome/blood
KW - Humans
KW - Hypoglycemic Agents/therapeutic use
KW - Insulin/blood
KW - Insulin Resistance
KW - Leptin/analogs & derivatives
KW - Male
KW - Middle Aged
KW - Pilot Projects
KW - Pioglitazone
KW - Postprandial Period/drug effects
KW - Thiazolidinediones/therapeutic use
U2 - 10.1016/j.metabol.2010.10.002
DO - 10.1016/j.metabol.2010.10.002
M3 - Journal article
C2 - 21081243
VL - 60
SP - 1045
EP - 1049
JO - Metabolism
JF - Metabolism
SN - 0026-0495
IS - 7
ER -
ID: 290520479