Project Details
Projekt
HyperICU. Effect of muscle wasting on global metabolite release and glucose homeostasis in patients with sarcopenia and critical illness
Subject Area
Endocrinology, Diabetology, Metabolism
Anaesthesiology
Anaesthesiology
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 536691227
Critically ill patients in the intensive care unit (ICU) suffer 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. Especially the muscle wasting in the ICU is associated with metabolic defects such as insulin resistance. The project aims to test in critically ill patients and in sarcopenic and non-sarcopenic women and men how they take up and release metabolites into the circulation, how their metabolome responds to an anabolic leucine challenge, and how they metabolize 13C glucose. We will investigate this using advanced methods of metabolic research, including arteriovenous metabolomics and metabolic flux analyses using stable isotope-labelled tracers. We have four specific objectives formulated as tasks to ourselves: (1) Identify metabolites that are taken up or released by the leg muscles of catabolic, critically ill patients at a time when atrophy is near maximal and at a time when atrophy is reversed (convalescence). (2) Identify metabolites that are taken up or released from control and resistance exercise-stimulated muscles of women and men with sarcopenia versus age and sex-matched controls without sarcopenia. (3) Measure the plasma metabolome response to 10 g leucine in critically ill patients versus age and sex-matched controls to see whether metabolite kinetics are a marker for anabolic responsiveness. (4) Measure the metabolite products in plasma made from 13C glucose in critically ill patients with muscle wasting or insulin resistance and after recovery from critical illness versus age and sex-matched controls. We expect that this project will help us to understand the metabolic mechanisms that explain how a fast (muscle atrophy during critical illness) and slow skeletal muscle atrophy (sarcopenia) affect muscular metabolite exchange. The first experiment will allow us to characterize the metabolite flooding that must occur when atrophying muscles degrade their biomass into metabolites that are then released into the circulation. The second experiment will yield data on the muscle metabolite uptake and release in elderlies with or without sarcopenia and how unilateral resistance training will stimulate anabolism and affect the metabolite exchange. The third experiment will show whether an anabolic responsiveness test is suitable for clinical practice to determine how well patients respond to an anabolic leucine stimulus and thus to personalize physical training and protein nutrition in critically ill patients in the future. The fourth experiment will show how glucose metabolism is changed in critically ill patients with ICU acquired weakness and insulin resistance. In summary, these experiments will help us understand how muscle atrophy causes metabolic defects as a basis of future therapies in critically ill and sarcopenic patients.
DFG Programme
Research Units
Subproject of
FOR 5795:
HyperMet: Effects of skeletal muscle hypertrophy and atrophy on metabolic health
Co-Investigators
Professor Dr. Jan Adriaan Graw; Dr. Sebastian Martini
