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Session 34 Oral Abstract Session Late Breakers II Session Time: Thursday, 9:30 am - 11:45 am Room 4B

10:00   LB11. Impaired Glucose Phosphorylation in Skeletal Muscle Causes Insulin Resistance in HIV-1 Infected Patients with Lipodystrophy G. M. N. Behrens, A.-R. Boerner, K. Weber, J. van den Hoff, J. Ockenga, G. Brabant, and R. E. Schmidt* Hannover Med. Sch., Germany Background: Insulin resistance is a frequently observed side effect of highly active antiretroviral therapy (HAART). Currently, very little is known about mechanisms or specific tissues involved. We aimed to identify possible defects in insulin-induced skeletal muscle glucose uptake and metabolism in HIV patients receiving HAART using positron-emission tomography. Methods: Whole body glucose disposal and oxidation were determined by combination of the euglycemic-hyperinsulinemic clamp technique and indirect calorimety in 6 patients on HAART and 6 untreated HIV patients. Body composition analysis was performed by anthropometric measurements as well as dual energy X-ray absorptiometry and body impedance analysis. Muscle glucose uptake of the thighs was measured simultaneously by dynamic F-18-fluorodeoxyglucose positron-emission tomography. Results: Whole body glucose disposal was significantly reduced in patients on HAART compared to untreated patients. Analysis of kinetic constants using a 3-compartment model indicated reduced skeletal glucose uptake caused by significantly impaired glucose phosphorylation in treated patients, but normal transmembrane glucose transport. Skeletal muscle glucose uptake was reduced by 79% in treated patients and explained 32% or 94% of whole body glucose disposal in patients on HAART and therapy-naïve patients, respectively. In addition, insulin-stimulated whole body oxidative and non-oxidative glucose disposal was significantly lower in the treated group. Suppressive insulin action on lipolysis was also impaired as was hepatic insulin clearance. Patients receiving HAART had signs of lipodystrophy. Conclusions: This is the first report providing in vivo evidence that in HIV patients receiving HAART, impaired glucose phosphorylation in the skeletal muscle contributes significantly to reduced insulin-mediated glucose uptake.

©2002 9th Conference on Retroviruses and Opportunistic Infections