760 Evaluation of the Oxidative Metabolism in Skeletal Muscle Using Carbon-11 Acetat PET in HIV-infected Patients with Lipodystrophy Syndrome G. M. N. Behrens*1,2, A-R. Boerner1, K. Weber1, J. van den Hoff1, J. Ockenga1, G. Brabant1, R. E. Schmidt1 1Hannover Med Sch, Germany and 2Walter and Eliza Hall Inst, Melbourne, Australia
Background: Lipodystrophy in HIV patients (pts) receiving HAART is frequently associated with abnormal lipid metabolism and insulin resistance. Mitochondrial toxicity induced by nucleoside-analogue reverse transcriptase inhibitors (NRTI) has been proposed to contribute to these side effects.
Methods: We performed carbon-11 acetate positron emission tomography (PET) to assess the oxidative capacity of the skeletal muscle in HIV pts with lipodystrophy syndrome compared to untreated HIV pts. Simultaneously, the pts underwent indirect calometry to measure oxygen consumption and resting energy expenditure (REE).
Results: Pts receiving HAART had peripheral fat loss and a higher percent truncal fat to percent extremity fat ratio. In addition, they were insulin resistant, had an impaired insulin-mediated suppression of FFA, a higher REE, and lower bound leptin levels. Lactate concentrations in lipodystrophic pts were significantly higher at basal and following oral glucose load. Similarly, FFA levels were elevated in these pts and correlated significantly to ketone bodies (r = 0.8, p = 0.001) suggesting impaired flux through the citric acid cycle. Using dynamic PET and a 2-compartment 2-rate constant model, we evaluated the oxidative phosphorylation capacity in the skeletal muscle. Rate constants for inward and outward transport of acetate were comparable between both groups as were the local metabolic rates (LMR) for acetate. Thus, impaired oxidative metabolism in skeletal muscle appears not to relevant in the pathogenesis of peripheral insulin resistance. We found a significant correlation between the oxygen consumption and the acetate LMR (r = 0.59, p = 0.039). This is in agreement with studies using carbon-11 acetate as a tracer of myocardial oxygen consumption.
Conclusions: Employing carbon-11 acetate PET, we found no evidence for impaired resting oxidative metabolism as a cause for peripheral insulin resistance in HIV pts with lipodystrophy. Increased FFA levels in these pts appear to be a result of increased lipolysis rather that impaired oxidative metabolization.
