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Published in: BMC Medicine 1/2021

Open Access 01-12-2021 | Research article

Metabolite profiles and the risk of metabolic syndrome in early childhood: a case-control study

Authors: Sandi M. Azab, Russell J. de Souza, Amel Lamri, Meera Shanmuganathan, Zachary Kroezen, Karleen M. Schulze, Dipika Desai, Natalie C. Williams, Katherine M. Morrison, Stephanie A. Atkinson, Koon K. Teo, Philip Britz-McKibbin, Sonia S. Anand

Published in: BMC Medicine | Issue 1/2021

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Abstract

Background

Defining the metabolic syndrome (MetS) in children remains challenging. Furthermore, a dichotomous MetS diagnosis can limit the power to study associations. We sought to characterize the serum metabolite signature of the MetS in early childhood using high-throughput metabolomic technologies that allow comprehensive profiling of metabolic status from a biospecimen.

Methods

In the Family Atherosclerosis Monitoring In earLY life (FAMILY) prospective birth cohort study, we selected 228 cases of MetS and 228 matched controls among children age 5 years. In addition, a continuous MetS risk score was calculated for all 456 participants. Comprehensive metabolite profiling was performed on fasting serum samples using multisegment injection-capillary electrophoresis-mass spectrometry. Multivariable regression models were applied to test metabolite associations with MetS adjusting for covariates of screen time, diet quality, physical activity, night sleep, socioeconomic status, age, and sex.

Results

Compared to controls, thirteen serum metabolites were identified in MetS cases when using multivariable regression models, and using the quantitative MetS score, an additional eight metabolites were identified. These included metabolites associated with gluconeogenesis (glucose (odds ratio (OR) 1.55 [95% CI 1.25–1.93]) and glutamine/glutamate ratio (OR 0.82 [95% CI 0.67–1.00])) and the alanine-glucose cycle (alanine (OR 1.41 [95% CI 1.16–1.73])), amino acids metabolism (tyrosine (OR 1.33 [95% CI 1.10–1.63]), threonine (OR 1.24 [95% CI 1.02–1.51]), monomethylarginine (OR 1.33 [95% CI 1.09–1.64]) and lysine (OR 1.23 [95% CI 1.01–1.50])), tryptophan metabolism (tryptophan (OR 0.78 [95% CI 0.64–0.95])), and fatty acids metabolism (carnitine (OR 1.24 [95% CI 1.02–1.51])). The quantitative MetS risk score was more powerful than the dichotomous outcome in consistently detecting this metabolite signature.

Conclusions

A distinct metabolite signature of pediatric MetS is detectable in children as young as 5 years old and may improve risk assessment at early stages of development.
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Literature
9.
go back to reference Andersen LB, Harro M, Sardinha LB, et al. Physical activity and clustered cardiovascular risk in children: a cross-sectional study (The European Youth Heart Study). Lancet. 2006;368:6.CrossRef Andersen LB, Harro M, Sardinha LB, et al. Physical activity and clustered cardiovascular risk in children: a cross-sectional study (The European Youth Heart Study). Lancet. 2006;368:6.CrossRef
20.
go back to reference Chavira-Suárez E, Rosel-Pech C, Polo-Oteyza E, et al. Simultaneous evaluation of metabolomic and inflammatory biomarkers in children with different body mass index (BMI) and waist-to-height ratio (WHtR). PLoS ONE. 2020;15(8):e0237917.CrossRef Chavira-Suárez E, Rosel-Pech C, Polo-Oteyza E, et al. Simultaneous evaluation of metabolomic and inflammatory biomarkers in children with different body mass index (BMI) and waist-to-height ratio (WHtR). PLoS ONE. 2020;15(8):e0237917.CrossRef
21.
go back to reference Perng W, Rifas-Shiman SL, Hivert M-F, Chavarro JE, Oken E. Branched chain amino acids, androgen hormones, and metabolic risk across early adolescence: a prospective study in project viva: BCAA, androgens, and metabolic risk in adolescence. Obesity. 2018;26(5):916–26. https://doi.org/10.1002/oby.22164.CrossRefPubMed Perng W, Rifas-Shiman SL, Hivert M-F, Chavarro JE, Oken E. Branched chain amino acids, androgen hormones, and metabolic risk across early adolescence: a prospective study in project viva: BCAA, androgens, and metabolic risk in adolescence. Obesity. 2018;26(5):916–26. https://​doi.​org/​10.​1002/​oby.​22164.CrossRefPubMed
26.
go back to reference Morrison KM, Anand SS, Yusuf S, et al. Maternal and pregnancy related predictors of cardiometabolic traits in newborns. Kirchmair R, ed. PLoS ONE. 2013;8(2):e55815.CrossRef Morrison KM, Anand SS, Yusuf S, et al. Maternal and pregnancy related predictors of cardiometabolic traits in newborns. Kirchmair R, ed. PLoS ONE. 2013;8(2):e55815.CrossRef
27.
go back to reference WHO Multicentre Growth Reference Study Group. WHO child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age. Methods and development. Geneva: World Health Organization; 2006. WHO Multicentre Growth Reference Study Group. WHO child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age. Methods and development. Geneva: World Health Organization; 2006.
30.
go back to reference Shanmuganathan M, Kroezen Z, Gill B, Azab S, de Souza RJ, Teo KK, et al. The maternal serum metabolome by multisegment injection-capillary electrophoresis-mass spectrometry: a high-throughput platform and standardized data workflow for large-scale epidemiological studies. Nat Protoc. 2021;(9):4538. https://doi.org/10.1038/s41596-021-00569-3. Shanmuganathan M, Kroezen Z, Gill B, Azab S, de Souza RJ, Teo KK, et al. The maternal serum metabolome by multisegment injection-capillary electrophoresis-mass spectrometry: a high-throughput platform and standardized data workflow for large-scale epidemiological studies. Nat Protoc. 2021;(9):4538. https://​doi.​org/​10.​1038/​s41596-021-00569-3.
31.
go back to reference Saoi M, Li A, McGlory C, et al. Metabolic perturbations from step reduction in older persons at risk for sarcopenia: plasma biomarkers of abrupt changes in physical activity. Metabolites. 2019;9(7):134.CrossRef Saoi M, Li A, McGlory C, et al. Metabolic perturbations from step reduction in older persons at risk for sarcopenia: plasma biomarkers of abrupt changes in physical activity. Metabolites. 2019;9(7):134.CrossRef
33.
go back to reference Wehrens R, Hageman JA, van Eeuwijk F, et al. Improved batch correction in untargeted MS-based metabolomics. Metabolomics. 2016;12(5):88.CrossRef Wehrens R, Hageman JA, van Eeuwijk F, et al. Improved batch correction in untargeted MS-based metabolomics. Metabolomics. 2016;12(5):88.CrossRef
36.
go back to reference de Souza RJ, Shanmuganathan M, Lamri A, et al. Maternal diet and the serum metabolome in pregnancy: robust dietary biomarkers generalizable to a multiethnic birth cohort. Curr Dev Nutr. 2020;4(10):nzaa144.CrossRef de Souza RJ, Shanmuganathan M, Lamri A, et al. Maternal diet and the serum metabolome in pregnancy: robust dietary biomarkers generalizable to a multiethnic birth cohort. Curr Dev Nutr. 2020;4(10):nzaa144.CrossRef
46.
go back to reference Hernandez-Baixauli J, Quesada-Vázquez S, Mariné-Casadó R, et al. Detection of early disease risk factors associated with metabolic syndrome: a new era with the NMR metabolomics assessment. Nutrients. 2020;12(3):806.CrossRef Hernandez-Baixauli J, Quesada-Vázquez S, Mariné-Casadó R, et al. Detection of early disease risk factors associated with metabolic syndrome: a new era with the NMR metabolomics assessment. Nutrients. 2020;12(3):806.CrossRef
Metadata
Title
Metabolite profiles and the risk of metabolic syndrome in early childhood: a case-control study
Authors
Sandi M. Azab
Russell J. de Souza
Amel Lamri
Meera Shanmuganathan
Zachary Kroezen
Karleen M. Schulze
Dipika Desai
Natalie C. Williams
Katherine M. Morrison
Stephanie A. Atkinson
Koon K. Teo
Philip Britz-McKibbin
Sonia S. Anand
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2021
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-021-02162-7

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