Metabolomic differences between critically Ill women and men

Abstract

Metabolism differs in women and men at homeostasis. Critically ill patients have profound dysregulation of homeostasis and metabolism. It is not clear if the metabolic response to critical illness differs in women compared to men. Such sex-specific differences in illness response would have consequences for personalized medicine. Our aim was to determine the sex-specific metabolomic response to early critical illness. We performed a post-hoc metabolomics study of the VITdAL-ICU trial where subjects received high dose vitamin D3 or placebo. Using mixed-effects modeling, we studied sex-specific changes in metabolites over time adjusted for age, Simplified Acute Physiology Score II, admission diagnosis, day 0 25-hydroxyvitamin D level, and 25-hydroxyvitamin D response to intervention. In women, multiple members of the sphingomyelin and lysophospholipid metabolite classes had significantly positive Bonferroni corrected associations over time compared to men. Further, multiple representatives of the acylcarnitine, androgenic steroid, bile acid, nucleotide and amino acid metabolite classes had significantly negative Bonferroni corrected associations over time compared to men. Gaussian graphical model analyses revealed sex-specific functional modules. Our findings show that robust and coordinated sex-specific metabolite differences exist early in critical illness.

The association of ambient temperature with depression in middle-aged and elderly people: a multicenter prospective repeat survey study in China

“…Due to physiological differences between men and women, such as sex hormones, body temperature regulation and immunity, men are better able to resist harsh environmental conditions [32,33]. For example, the metabolic rate of men is higher than that of women, the higher the metabolic rate, the more heat is produced and the stronger the resistance to cold [34]. In addition, women have smaller and weaker muscles than men, higher muscle mass produces more heat, so women are more sensitive to cold perception [35].…”

Vitamin D in critical care: where are we now and what is next?

“…With a meaningful increase of 25(OH)D levels of more than 15 ng/ml, significant changes in lipid metabolism (sphingomyelin, plasmalogen, and lysophospholipid metabolite classes) were associated with decreased 28-day mortality. Early on, sex-specific differences in metabolomic response are present [41 ▪▪ ]. Many completed and ongoing vitamin D RCTs assumed ridiculously large, unplausible treatment effects, allowing for small sample sizes and feasibility of a trial, usually in an academic setting.…”