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6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV25–28 October 2004 - Washington, DC, USA |
PLASMA ADIPONECTIN AND IL-6 PREDICT INSULIN SENSITIVITY IN PATIENTS WITH HIV INFECTION INDEPENDENTLY OF BODY FAT DISTRIBUTION
Antiviral Therapy 2004; 9(6):L5 (abstract no. 4)
DN Reeds, KE Yarasheski, WT Cade, BW Patterson, WG Powderly and S Klein
Washington University School of Medicine, St Louis, Mo., USA
BACKGROUND: Metabolic abnormalities occur in 40% of patients who receive highly active antiretroviral therapy (HAART). It is unknown whether adipokines are related to metabolic abnormalities in these patients.
OBJECTIVE: To examine the relationships between plasma IL-6 and adiponectin concentration, and insulin sensitivity in HIV+ patients with (HIV-LD) or without (HIV-NC) lipodystrophy (Carr et al., Lancet. 2003 Mar 1;361(9359):726-35.
METHODS: We studied 24 men matched for age, BMI and body composition: 12 with HIV-LD receiving HAART (six receiving protease inhibitors) and 12 with HIV-NC (six receiving HAART, six naïve to antiretroviral therapy). Intravenous infusions of 6,6–2H2 glucose and 2,2–2H2 palmitate were used to measure plasma glucose and palmitate rates of appearance (Ra) and glucose disposal rate (Rd), during euglycaemia and graded insulin infusions [20 mU·m–2·min–1 (stage 1) and 50 mU·m–2·min–1 (stage 2)]. Fat-free mass (FFM) was assessed by dual energy X-ray absorptiometry.
RESULTS: Fasting HOMA was greater in HIV-LD than HIVNC (3.0 ±0.4 vs 1.3 ±2.1, P<0.001). Glucose Ra (4.7 ±0.9 µmol·kgFFM–1·min–1 vs 2.6 ±0.4 µmol·kgFFM–1·min–1, P=0.008) and palmitate Ra (0.54 ±0.06 µmol·kgFFM–1·min–1 vs 0.27 ±0.02 µmol·kgFFM–1·min–1, P<0.001) were greater, and glucose Rd (39 ±3 µmol·kgFFM–1·min–1vs 58 ±4µmol·kgFFM–1·min–1, P=0.001) was lower in HIV-LD than HIV-NC, during stage 1 and stage 2, respectively. Basal plasma adiponectin concentration was ~40% lower in patients with HIV-LD than HIV-NC (4.2 ±0.6 pg/ml vs 7.4 ±1 pg/ml, P=0.02), and was ~40% lower in HIV-NC patients receiving HAART than those naïve to therapy (5.4 ±1.1 mg/dl vs 9.4 ±1.6 pg/ml, P=0.07). Adiponectin concentration correlated with serum HDL (r=0.47, P=0.03) and triglyceride (r= –0.45, P=0.02) concentrations, stage 1 glucose Ra (r= –0.40, P=0.05) and stage 2 glucose Rd (r=0.52, P=0.008). Plasma IL-6 concentration was not different between groups with HIV infection. Plasma IL-6 concentration correlated with glucose Rd (r= –0.51, P=0.01) during stage 2 and palmitate Ra (r=0.37, P=0.08) during stage 1. These correlations persisted after correction for age, limb fat mass and duration of HAART, HIV infection and PI exposure.
CONCLUSION: Plasma adiponectin and IL-6 concentrations independently predict the sensitivity of stimulation of glucose disposal and suppression of lipolysis by insulin in patients with HIV infection. Use of HAART is associated with a reduction in plasma adiponectin concentration.
2004-10-25
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