Muscle glycogen metabolism is rapidly dysregulated in critical illness, which may have implications for muscle ATP resynthesis and ICU acquired weakness: Supplemental data

This is the supplemental data for the article "Muscle glycogen metabolism is rapidly dysregulated in critical illness, which may have implications for muscle ATP resynthesis and ICU acquired weakness", accepted for publication in the American Journal of Physiology-Endocrinology and Metabolism.<b>Article abstract</b>The association of perturbed skeletal muscle metabolism with ICU acquired weakness (ICUAW) is not clear. The objective of the present study was to characterise temporal changes in skeletal muscle mitochondrial function, ATP concentration, and substrate utilisation during and up to 6 months post ICU admission in critically ill patients, and to delineate mechanisms underpinning ICUAW by comparing the expression of genes involved in skeletal muscle mitochondrial function and substrate utilisation in the critically ill patients to control groups that had either undergone elective surgery or leg immobilisation (i.e. muscle disuse). The study design was a randomised controlled trial of functional electrical stimulation-assisted cycle ergometry (FESCE) vs. standard care, with skeletal muscle mitochondrial respirometry defined <i>a priori</i><i> </i>in a nested sub-group of patients as the primary outcome. Mitochondrial respirometry did not change 7 days or 6 months after ICU admission and was not impacted by FESCE. However, a 20% reduction in muscle ATP content by day 7 of ICU stay persisted after 6 months and tended to associate with ICUAW (<i>P</i>=0.078, R²=0.582). Moreover, a 40% lower muscle glycogen and 2.5-fold greater muscle lactate were observed earlier at day 1 compared to elective surgery patients. These changes reflected expression of genes related to glycogen metabolism when disuse was accounted for, and of which a greater expression of the gene encoding glycogen phosphorylase (PYGM) was predictive of mortality. We conclude that muscle glycogen metabolism is rapidly dysregulated in critical illness, which may have implications for muscle ATP resynthesis and ICUAW.