8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV San Francisco, California - September 24 - 26, 2006

EFFECTS OF LEPTIN TREATMENT ON GLUCOSE AND LIPID METABOLISM AND FAT DISTRIBUTION IN HIV-INFECTED PATIENTS WITH LIPOATROPHY AND HYPOLEPTINEMIA

Antiviral Therapy 2006; 11:L15 (abstract no. 22)

H Khatami¹, K Mulligan¹, J-M Schwarz^1,2, GK Sakkas¹, AM DePaoli³, S Park¹, S Kim¹, VW Tai¹, M Wen¹, GA Lee¹, C Grunfeld¹ and M Schambelan^1
1University of California San Francisco, San Francisco, CA, USA; ²Touro University, Vallejo, CA, USA; ³Amgen Inc., Thousand Oaks, CA, USA

OBJECTIVE: Leptin treatment improved glucose and lipid metabolism in persons with non-HIV lipodystrophy. We performed an open-label, proof-of-principle study to determine whether leptin could produce similar metabolic benefits in HIV-infected patients with lipoatrophy.

METHODS: Eight HIV-positive men with lipoatrophy (± fat accumulation), hypoleptinemia (<3 ng/ml), dyslipidemia, and insulin resistance received recombinant human leptin (Amgen, Inc.) for 6 months (0.01 mg/kg BID for 3 months, followed by 0.03 mg/kg BID for 3 months). Glucose and lipid metabolism was assessed under fasting conditions and during a euglycaemic, hyperinsulinemic clamp with stable isotope infusions measuring endogenous glucose production, gluconeogenesis, glycogenolysis, and lipolysis at baseline and month 6. Body composition was assessed by DEXA and MRI. Data are the mean ±SE.

RESULTS: Hepatic insulin sensitivity improved, as evidenced by significant decreases in fasting insulin (21 ±3 to 16 ±2 µIU/ml at baseline and month 6, respectively, P=0.039), HOMA-IR (5.6 ±0.8 to 4.1 ±0.6, P=0.036), endogenous glucose production (2.78 ±0.07 to 2.47 ±0.07 mg/kg/min, P=0.005), and glycogenolysis (2.15 ±0.07 to 1.89 ±0.06 mg/kg/min, P=0.029). Leptin treatment also improved the ability of insulin to suppress endogenous glucose production (49 ±7 to 69 ±2% suppression, P=0.018), glycogenolysis (43 ±8 to 64 ±4%, P=0.0.023), and gluconeogenesis (72 ±6 to 87 ±3%, P=0.019) during the euglycaemic hyperinsulinemic clamp. In contrast, although peripheral glucose uptake (clamp) improved in some subjects, overall there was no statistically significant change. Wholebody lipolysis decreased significantly under fasting conditions (0.20 ±0.02 to 0.15 ±0.02 mg/kg/min; P=0.022), suggesting an effect of leptin on adipose tissue. Dyslipidemia improved (fasting cholesterol -39 ±12 mg/dl, P=0.018; triglycerides -160 ±92 mg/dl, P=0.127). Visceral fat (MRI; L4-L5) decreased in all subjects (183 ±24 to 129 ±24 cm², P=0.001), whereas neither subcutaneous abdominal fat (MRI) nor limb fat (DEXA) changed significantly. Weight and LBM tended to decrease (-2.0 ±1.0 and -1.6 ±0.9 kg, P=0.098 and 0.139, respectively). Leptin was well tolerated by all subjects.

CONCLUSIONS: In this pilot study, leptin treatment was associated with improvements in insulin sensitivity in the liver but not in whole-body glucose uptake. Dyslipidemia improved. Visceral fat decreased with no apparent exacerbation of peripheral lipoatrophy, suggesting that leptin may have a depot-specific effect in adipose tissue.

Grant support: NIH (DK63640, DK66999, DK54615, RR00083); Amgen, Inc.

Download PDF of this abstract.

2006-09-24
22

Copyright © 2006 - International Medical Press Ltd. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Medical Editor, International Medical Press, 36 St Mary-at-Hill, London EC3R 8DU, United Kingdom.