TY - JOUR

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 -