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Mäkinen, VP., Kettunen, J., Lehtimäki, T. et al. Longitudinal metabolomics of increasing body-mass index and waist-hip ratio reveals two dynamic patterns of obesity pandemic. Int J Obes 47, 453–462 (2023). https://doi.org/10.1038/s41366-023-01281-w

Longitudinal metabolomics of increasing body-mass index and waist-hip ratio reveals two dynamic patterns of obesity pandemic

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Author: Mäkinen, Ville-Petteri1,2,3,4; Kettunen, Johannes1,2,5,6; Lehtimäki, Terho7;
Organizations: 1Systems Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland
2Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland
3Computational and Systems Biology Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
4Australian Centre for Precision Health, University of South Australia, Adelaide, SA, Australia
5Biocenter Oulu, Oulu, Finland
6Department of Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
7Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
8Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
9Department of Medicine, University of Turku, Turku, Finland
10Division of Medicine, Turku University Hospital, Turku, Finland
11Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland
12Estonian Genome Center, University of Tartu, Tartu, Estonia
13Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland
14Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
15Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK
16Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
17Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
18Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
19NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2023081595869
Language: English
Published: Springer Nature, 2023
Publish Date: 2023-08-15
Description:

Abstract

Background/Objectives: This observational study dissects the complex temporal associations between body-mass index (BMI), waist-hip ratio (WHR) and circulating metabolomics using a combination of longitudinal and cross-sectional population-based datasets and new systems epidemiology tools.

Subjects/Methods: Firstly, a data-driven subgrouping algorithm was employed to simplify high-dimensional metabolic profiling data into a single categorical variable: a self-organizing map (SOM) was created from 174 metabolic measures from cross-sectional surveys (FINRISK, n = 9708, ages 25–74) and a birth cohort (NFBC1966, n = 3117, age 31 at baseline, age 46 at follow-up) and an expert committee defined four subgroups of individuals based on visual inspection of the SOM. Secondly, the subgroups were compared regarding BMI and WHR trajectories in an independent longitudinal dataset: participants of the Young Finns Study (YFS, n = 1286, ages 24–39 at baseline, 10 years follow-up, three visits) were categorized into the four subgroups and subgroup-specific age-dependent trajectories of BMI, WHR and metabolic measures were modelled by linear regression.

Results: The four subgroups were characterised at age 39 by high BMI, WHR and dyslipidemia (designated TG-rich); low BMI, WHR and favourable lipids (TG-poor); low lipids in general (Low lipid) and high low-density-lipoprotein cholesterol (High LDL-C). Trajectory modelling of the YFS dataset revealed a dynamic BMI divergence pattern: despite overlapping starting points at age 24, the subgroups diverged in BMI, fasting insulin (three-fold difference at age 49 between TG-rich and TG-poor) and insulin-associated measures such as triglyceride-cholesterol ratio. Trajectories also revealed a WHR progression pattern: despite different starting points at the age of 24 in WHR, LDL-C and cholesterol-associated measures, all subgroups exhibited similar rates of change in these measures, i.e. WHR progression was uniform regardless of the cross-sectional metabolic profile.

Conclusions: Age-associated weight variation in adults between 24 and 49 manifests as temporal divergence in BMI and uniform progression of WHR across metabolic health strata.

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Series: International journal of obesity
ISSN: 0307-0565
ISSN-E: 1476-5497
ISSN-L: 0307-0565
Volume: 47
Issue: 6
Pages: 453 - 462
DOI: 10.1038/s41366-023-01281-w
OADOI: https://oadoi.org/10.1038/s41366-023-01281-w
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Article
Funding: This work was supported by Academy of Finland, Novo Nordisk foundation, Oulu Health and Wellfare Center, Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, ERDF European Regional Development Fund, EU Horizon 2020, EU Research Council and following foundations: Sigrid Juselius, Finnish Cardiovascular Research, Juho Vainio, Paavo Nurmi, Finnish Cultural, Tampere Tuberculosis, Emil Aaltonen, Yrjö Jahnsson, Signe and Arne Gyllenberg, and Finnish Diabetes Research. The Young Finns Study has been financially supported by the Academy of Finland grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (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; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements No 848146 for To Aition and grant agreement 755320 for TAXINOMISIS; European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation and Finnish Society of Clinical Chemistry. Open Access funding provided by University of Oulu including Oulu University Hospital.
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