Highlights
- •Critically ill females have the highest increase and attenuated reduction of amino acid pathways.
- •Large differences between males and females exist specifically for glutamine and glutamate whole body productions.
- •Severely ill females showed a suppressed metabolism. Compartmental analysis supported the observations.
Abstract
Background
The trajectory from healthy to critical illness is influenced by numerous factors,
including metabolism, which differs substantially between males and females. Whole
body protein breakdown is substantially increased in critically ill patients, but
it remains unclear whether there are sex differences that could explain the different
health outcomes. Hence, we performed a secondary analysis of a study, where we used
a novel pulse isotope method in critically ill and matched healthy males and females.
Methods
In 51 critically ill ICU patients (26 males, 15 females) and 49 healthy controls (36
males and 27 females), we assessed their general and disease characteristics and collected
arterial(ized) blood in the postabsorptive state after pulse administration of 8 ml
of a solution containing 18 stable AA tracers. In contrast to the original study,
we now fitted the decay curves and calculated non-compartmental whole body amino acid
production (WBP) and compartmental measurements of metabolism, including intracellular
amino acid production. We measured amino acid enrichments and concentrations by LC-MS/MS
and derived statistics using AN(C)OVA.
Results
Critically ill males and females showed an increase in the WBP of many amino acids,
including those related to protein breakdown, but females showed greater elevations,
or in the event of a reduction, attenuated reductions. Protein breakdown-independent
WBP differences remained between males and females, notably increased glutamine and
glutamate WBP. Only severely ill females showed a lower increase in WBP of many amino
acids in comparison to moderately ill females, suggesting a suppressed metabolism.
Compartmental analysis supported the observations.
Conclusions
The present study shows that females have a different response to critical illness
in the production of several amino acids and changes in protein breakdown, observations
made possible using our innovative stable tracer pulse approach.
Clinical trial registry
Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).
Abbreviations:
BCAA (branched-chain amino acids), BIA (bioimpedance analysis), BMI (body mass index), FFM (fat-free mass), hsCRP (high sensitivity C-reactive protein), ICU (intensive care unit), PHE (phenylalanine), REE (resting energy expenditure), SOFA (systemic organ failure assessment), TRP (tryptophan), TTR (tracer/tracee ratio), TYR (tyrosine), WBP (whole body production rate)Keywords
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Article info
Publication history
Published online: January 26, 2023
Accepted:
January 10,
2023
Received:
October 25,
2022
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
