ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2020) 17 11.11 | DOI: 10.1530/ey.17.11.11

Department of Pediatrics and Pediatric Endocrinology, School of Medicine in Katowice, Medical University of Silesia, Upper Silesia Children’s Care Health Centre, Katowice, Poland, agawlik@mp.pl


To read the full abstract: Diabetes Care. 2020;43(2):405–410. doi: https://pubmed.ncbi.nlm.nih.gov/31727688/

Here, Gawlik et al. describe the urinary steroid metabolomic profile associated with insulin resistance (IR) as assessed in a cohort of 87 non-syndromic obese children and adolescents.

To explore the previously defined novel concept of a disease-specific steroid metabolomic signature (1), these authors investigated the steroid metabolomic profile (31 steroid metabolites) using gas chromatography-mass spectrometry in urine samples from obese children. 24-h urine collection is recognized as a stable and reproducible method for steroid metabolite assessment. Interestingly, the metabolomic profile of the children with IR (20/87 children) showed significantly higher levels of steroids from all three adrenal pathways (adrenal androgens, glucocorticoids and mineralocorticoids) compared to children without IR. In addition, children with IR presented higher 5α-reductase and 21-hydroxylase activities, and lower 11βHSD1 activity.

It is well accepted that glucocorticoids can induce IR. The findings here demonstrate convincingly that IR and hyperinsulinemia are associated with higher adrenal steroid production. Based on these findings, the authors suggest that the adrenal gland per se is a target of IR or hyperinsulinemia. The underlying regulation is complex and one obvious regulatory mechanism is direct stimulation by insulin of the expression of steroidogenic factor-1 and steroidogenetic genes, independent of the CRH-ACTH-MC2R-PKA pathway. Thereby, hyperinsulinemia in IR may directly increase generation of adrenal hormones. Given the fact, that glucocorticoids induce IR, the authors propose a vicious cycle involving these factors.

Due to the small sample size, more studies are needed to verify these exciting results and the innovative underlying concept. Identifying the IR-specific steroid metabolomic profile of obese children may facilitate the design of effective and personalized therapeutic strategies. It would be interesting to investigate whether children with IR may benefit from e.g. a pharmacological intervention to reduce their exaggerated adrenal steroidogenesis.

Reference:

1. Gawlik A, Shmoish M, Hartmann MF, Malecka-Tendera E, Wudy SA, Hochberg Z. Steroid Metabolomic Disease Signature of Nonsyndromic Childhood Obesity. The Journal of clinical endocrinology and metabolism 2016;101 (11):4329–37.

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