A1 Refereed original research article in a scientific journal
Metabolic transition from childhood to adulthood based on two decades of biochemical time series in three longitudinal cohorts
Authors: Mäkinen, Ville-Petteri; Kähönen, Mika; Lehtimäki, Terho; Hutri, Nina; Rönnemaa, Tapani; Viikari, Jorma; Pahkala, Katja; Rovio, Suvi; Niinikoski, Harri; Mykkänen, Juha; Raitakari, Olli; Ala-Korpela, Mika
Publisher: Oxford University Press
Publication year: 2025
Journal: International Journal of Epidemiology
Journal name in source: International journal of epidemiology
Journal acronym: Int J Epidemiol
Article number: dyaf026
Volume: 54
Issue: 2
ISSN: 0300-5771
eISSN: 1464-3685
DOI: https://doi.org/10.1093/ije/dyaf026
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://academic.oup.com/ije/article/54/2/dyaf026/8096630?login=true
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/491906236
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
Background: This is the first large-scale longitudinal study of children that describes the temporal trajectories of an extensive collection of metabolic measures that are relevant for lifelong cardiometabolic risk. We also provide a comprehensive picture on how metabolism develops into mature adult sex-specific phenotypes.
Methods: Children born in 1962-92 were recruited by three European studies (n = 20 377 eligible). Biochemical data for ages 0-26 years were available for n = 14 958 participants (n = 8385 with metabolomics). Age associations for 168 metabolic measures (6 physiological traits, 6 clinical biomarkers, and 156 serum metabolomics measures) were determined by using curvilinear regression. Puberty effects were calculated by using logistic regression of biological sex for pre- and post-pubertal age strata.
Results: Age-specific concentrations were reported for all measures. Nonlinear age associations were typical, including insulin (R2 = 20.7% ±0.6% variance explained ±SE), glycerol (13.3% ±1.3%), glycoprotein acetyls (40.3% ±1.5%), and branched-chain amino acids (19.5% ±1.6%). Apolipoprotein B was not associated with age (0.7% ±0.4%). Multivariate modeling indicated that boys diverged from girls metabolically during ages 13-17 years. Puberty effects were observed for large high-density lipoprotein cholesterol (P = 8.5 × 10-288), leucine (P < 2.3 × 10-308), glutamine (P < 2.3 × 10-308), albumin (P = 1.7 × 10-161), docosahexaenoic acid (P = 5.2 × 10-50), and sphingomyelin (P = 4.4 × 10-90).
Conclusion: Novel associations between emerging cardiometabolic risk factors, such as amino acids and glycoprotein acetyls, and growth and puberty were observed. Conversely, apolipoprotein B was stable, which favors its utility for early assessments of lifetime cardiovascular risk.
Keywords: amino acids; apolipoprotein B; cardiovascular risk factor; children; inflammation; insulin; lipids; longitudinal; metabolism; puberty.
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Funding information in the publication:
This study was supported by a research grant from the Sigrid Juselius Foundation, the Finnish Foundation for Cardiovascular Research, and the Research Council of Finland (grant no. 357183). The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for the ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (URL: http://www.bristol.ac.uk/alspac/ external/documents/grant-acknowledgements.pdf). Specific grants that apply here include 076467/Z/05/Z, CS/15/6/ 31468, 086676/Z/08/Z, 076467/Z/05/Z, 076467/Z/05/Z, PG106/145, and R01 DK077659. This publication is the work of the authors and V.P.M. will serve as the guarantor for the contents of this paper. The YFS has been financially supported by the Academy of Finland: grants 356405, 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjo € Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; pBETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); CVDLink (EU grant no. 101137278) and the Jane and Aatos Erkko Foundation.
