3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 23-26 October 2001, Athens, Greece

IMPAIRED GLUCOSE TRANSPORT AND PHOSPHORYLATION IN SKELETAL MUSCLE ASSESSED BY [18F] FLUORODESOXY-GLUCOSE POSITRON EMISSION TOMOGRAPHY IN HIV-PATIENTS ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

Antiviral Therapy 2001; 6(Suppl. 4):4 (abstract no.4)

GMN Behrens, K Weber, A-R Boerner, H Hecker, J Ockenga, G Brabant, M Stoll and RE Schmidt
Hannover Medical School, Hannover, Germany

BACKGROUND: Site and mechanism of insulin resistance observed during highly active antiretroviral therapy (HAART) are unknown.

OBJECTIVE: To investigate insulin-induced glucose uptake and metabolism of skeletal muscle and beta-oxidation by positron-emission tomography (PET) for identification of defects of muscle uptake and metabolism in HIV patients receiving HAART compared with therapy-naïve HIV patients.

METHODS: Muscle glucose uptake of the thighs was measured by dynamic [¹⁸F] fluorodesoxyglucose PET in six patients on HAART and six untreated HIV patients. Muscular beta-oxidation was determined by assessment of [¹¹c] acetate clearance. Whole body glucose disposal and oxidation were determined by euglycemic-hyperinsulinemic clamp and indirect calorimetry. Body composition analysis included DEXA, BIA and anthropometric measurements. Various immunological and metabolical parameters were assessed.

RESULTS: Whole body glucose disposal was significantly reduced in patients on HAART (1.47±0.38mg/kg/min) compared with untreated patients (4.07±0.90 mg/kg/min; P=0.025). Analysis of kinetic constants using a three-compartment model .indicated reduced skeletal glucose transport and significantly impaired glucose phosphorylation in treated patients (0.009±0.001 versus 0.1±0.004, P<0.01). These patients had signs of lipodystrophy (for example, higher% truncal fat to% extremity fat ratio (2.9±0.3 versus 1.3±0.1; P=0.0002). In addition, insulin-stimulated whole body oxidative disposal was lower in the treated group compared with basal conditions. The [¹¹c] acetate PET revealed no difference in beta-oxidation capacity or insulin stimulated blood flow between both groups.

CONCLUSIONS: This is the first report providing in vivo evidence that in HIV patients receiving HAART both reduced glucose uptake and impaired intracellular glucose phosphorylation contribute to insulin resistance. Our study provides evidence that skeletal muscle is the primary site of insulin resistance on HAART.

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