ESPE Yearbook of Paediatric Endocrinology

Biomolecules 2021;11:1746 doi: 10.3390/biom11121746

Brief summary: Comprehensive steroid profiling of pregnant women with and without gestational diabetes mellitus (GDM) during late gestation revealed specific GDM-related steroidomic changes, linking the maternal compartment to GDM pathophysiology and highlighting the interaction between GDM and the stage of gestation.

It is well known that GDM has serious health implications for both the mother and the developing fetus, as it would be expected with induced glucose intolerance leading to persistent hyperglycaemia and insulin resistance that signifies this condition [Plows et al., 2018]. This study evaluated the alterations in steroid levels in women with GDM at crucial stages of late gestation and at labor, to better understand the possible hormone role-players involved in neuroactive and immunomodulatory processes. The prelude to this study was the development of an analytical method that quantifies 100 endogenous steroids in human serum [Hill et al., 2019] – an impressive task which rewarded the authors with a powerful tool to perform extensive steroid profiling of in vivo samples.

The authors found altered levels of 49 steroids between women with and without GDM. These differences show that the pathophysiology of GDM, in terms of steroidomics, is dominant in the maternal compartment compared to the fetal-placental compartment (determined through the analysis of mixed umbilical cord blood). Steroid hormones involved in multiple steroid pathways, together with those reduced by hepatic enzymes were significantly different. In addition, progesterone was confirmed as a pro-diabetogenic steroid, as levels were substantially higher in GDM women, but on the contrary, its levels were lower at labor. These authors complete an in-depth analysis of the biochemistry, entailing the production of the steroid metabolites which were differentially measured and ultimately relate these steroid levels to steroid metabolic enzymes.

Any steroidomic approach to understanding complex steroid metabolic pathways is a large undertaking, and even more so when it is applied to a disease condition. Unfortunately, the lack of sampling before 24 weeks gestation makes it difficult to understand if any changes might contribute to GDM pathogenesis rather than being consequential. However, such investigations are expected to substantially increase in the future as our analytical capabilities improve and will surely provide data from which newer steroid signalling cascades can be modelled and novel steroid biomarkers identified.

References: 1. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci. 2018;19:3342, doi: 10.3390/ijms19113342. 2. Hill M, Hána Jr V, Velíková M, Pa�ízek A, Kolátorová L, Vítkü J, Škodová T, Šimková M, Šimják P, Kancheva R, Koucký M, Kokrdová Z, Adamcová K, Černý A, Hájek Z, Dušková M, Blunt J, Stárka L. A method for determination of one hundred endogenous steroids in human serum by gas chromatography–tandem mass spectrometry. Physiol Res. 2019;68:179–207, https://doi.org/10.33549/physiolres.934124.