HyperICU - Effect of muscle wasting on global metabolite release and glucose homeostasis in patients with sarcopenia and critical illness

Critically ill patients in the intensive care unit (ICU) suffer from fast muscle atrophy of ≈2% of muscle mass per day. In contrast, patients with sarcopenia experience slow muscle atrophy of less than 1% per year. Notably, muscle wasting in the ICU is associated with metabolic defects, such as insulin resistance. The aim of Project P07 is to use advanced methods of metabolic research to study the metabolism in controls versus patients with sarcopenia and critical illness. To identify metabolites released by atrophying muscles of critically ill and sarcopenic patients, we will, in the first and second experiments, measure global metabolite release from leg muscles through arteriovenous metabolomics. Third, we will test the hypothesis that the kinetics of blood metabolite changes following an anabolic leucine challenge are a biomarker of a patient's anabolic responsiveness. Fourth, we will measure the metabolization of [13C]-glucose in critically ill patients with versus without insulin resistance. These experiments will help us understand how muscle atrophy leads to metabolic defects, providing a basis for future therapies in these patients.