Metabolomic differences between critically Ill women and men.

Area of Science:

• Biochemistry
• Metabolomics
• Critical Care Medicine

Background:

• Metabolism exhibits sex-based differences under normal physiological conditions (homeostasis).
• Critical illness causes significant homeostatic and metabolic dysregulation.
• The existence and extent of sex-specific metabolic responses to critical illness remain unclear.

Purpose of the Study:

• To investigate sex-specific metabolomic alterations during the early stages of critical illness.
• To identify distinct metabolic profiles between women and men in intensive care unit (ICU) settings.

Main Methods:

• A post-hoc metabolomics analysis was conducted on data from the VITdAL-ICU trial.
• Mixed-effects modeling was employed to analyze sex-specific metabolite changes over time.
• Statistical adjustments were made for age, disease severity (Simplified Acute Physiology Score II), diagnosis, and vitamin D levels.

Main Results:

• Significant sex-specific differences in metabolite levels were observed early in critical illness.
• Women showed increased levels of sphingomyelin and lysophospholipid metabolites compared to men.
• Men exhibited higher levels of acylcarnitine, androgenic steroids, bile acids, nucleotides, and amino acids relative to women.
• Sex-specific functional modules were identified using Gaussian graphical models.

Conclusions:

• Critical illness elicits robust and coordinated sex-specific metabolic responses.
• These findings highlight the importance of considering sex in the context of critical illness metabolism.
• The identified sex-specific metabolic differences have implications for personalized medicine strategies in critical care.