Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Ari V. Ahola-Olli, View ORCID ProfileLinda Mustelin, View ORCID ProfileMaria Kalimeri, View ORCID ProfileJohannes Kettunen, Jari Jokelainen, View ORCID ProfileJuha Auvinen, Katri Puukka, Aki S. Havulinna, Terho Lehtimäki, Mika Kähönen, View ORCID ProfileMarkus Juonala, Sirkka Keinänen-Kiukaanniemi, View ORCID ProfileVeikko Salomaa, View ORCID ProfileMarkus Perola, View ORCID ProfileMarjo-Riitta Järvelin, View ORCID ProfileMika Ala-Korpela, View ORCID ProfileOlli Raitakari, View ORCID ProfilePeter Würtz
doi: https://doi.org/10.1101/513648
Ari V. Ahola-Olli
1Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
2Department of Internal Medicine, Satakunta Central Hospital, Pori, Finland.
3Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Linda Mustelin
3Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
4Nightingale Health Ltd, Helsinki, Finland.
5Department of Public Health, University of Helsinki, Helsinki, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Linda Mustelin
Maria Kalimeri
4Nightingale Health Ltd, Helsinki, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Maria Kalimeri
Johannes Kettunen
6Centre for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
7Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland
8NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Johannes Kettunen
Jari Jokelainen
6Centre for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
9Unit of Primary Health Care and Medical Research Center, Oulu University Hospital, Oulu, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juha Auvinen
6Centre for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
9Unit of Primary Health Care and Medical Research Center, Oulu University Hospital, Oulu, Finland.
10Oulunkaari Primary Health Care Unit, Ii, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Juha Auvinen
Katri Puukka
11University of Oulu and Medical Research Center Oulu, Oulu, Finland; Nordlab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aki S. Havulinna
3Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
12National Institute for Health and Welfare, Helsinki, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Terho Lehtimäki
13Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mika Kähönen
14Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Markus Juonala
15Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Markus Juonala
Sirkka Keinänen-Kiukaanniemi
6Centre for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
9Unit of Primary Health Care and Medical Research Center, Oulu University Hospital, Oulu, Finland.
16Healthcare and Social Services of Selanne, Pyhasalmi, Finland
17Healthcare Services of City of Oulu, Diabetes Unit, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Veikko Salomaa
12National Institute for Health and Welfare, Helsinki, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Veikko Salomaa
Markus Perola
3Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
12National Institute for Health and Welfare, Helsinki, Finland.
18Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Markus Perola
Marjo-Riitta Järvelin
6Centre for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
9Unit of Primary Health Care and Medical Research Center, Oulu University Hospital, Oulu, Finland.
19Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
20Biocenter Oulu, University of Oulu, Finland
21Department of Life Sciences, College of Health and Life Sciences, Brunel University London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marjo-Riitta Järvelin
Mika Ala-Korpela
7Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland
8NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
22Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
23Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
24Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
25Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, VIC, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mika Ala-Korpela
Olli Raitakari
1Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
26Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Olli Raitakari
Peter Würtz
4Nightingale Health Ltd, Helsinki, Finland.
27Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Peter Würtz
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Objective Advances in metabolomics now allow high-throughput biomarker profiling of large population studies. We aimed to identify circulating metabolic biomarkers predictive of type 2 diabetes in young adults.

Methods Nuclear magnetic resonance metabolomics was used to quantify 229 metabolic measures in 11,896 individuals from four Finnish cohorts (mean age 33 years, range 24–45). Associations between baseline metabolites and risk of type 2 diabetes onset during 8–15 years of follow-up (392 incident cases) were assessed by logistic regression adjusted for sex, age, body mass index, and fasting glucose.

Results Out of 229 metabolic measures, 113 were associated with incident diabetes in meta-analysis of the four cohorts (P<0.0009; odds ratios per 1-SD: 0.59–1.50). Among the strongest predictors of diabetes risk were branched-chained and aromatic amino acids (odds ratios 1.31–1.33), triglyceride fractions within the largest very-low-density lipoprotein particles (VLDL; odds ratios 1.33–1.50)), as well as linoleic omega-6 fatty acids (odds ratio 0.75) and free cholesterol in large high-density lipoprotein particles (HDL; odds ratio 0.59). A biomarker score comprised of phenylalanine, free cholesterol in large HDL, and the ratio of cholesteryl esters to total lipids in large VLDL was predictive of the risk for future diabetes in an independent validation cohort (odds ratio 10.1 [95% confidence intervals 4.2-24.1] comparing individuals in upper vs lower fifth of biomarker score). Adjustment for routine lipids and insulin attenuated the odds ratio to 5.8 [2.2-15.1].

Conclusions Metabolic aberrations across multiple molecular pathways are predictive of the long-term risk of type 2 diabetes in young adults. Comprehensive metabolic profiling may potentially help targeting preventive interventions for young asymptomatic individuals at increased risk for type 2 diabetes.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted January 08, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts
Ari V. Ahola-Olli, Linda Mustelin, Maria Kalimeri, Johannes Kettunen, Jari Jokelainen, Juha Auvinen, Katri Puukka, Aki S. Havulinna, Terho Lehtimäki, Mika Kähönen, Markus Juonala, Sirkka Keinänen-Kiukaanniemi, Veikko Salomaa, Markus Perola, Marjo-Riitta Järvelin, Mika Ala-Korpela, Olli Raitakari, Peter Würtz
bioRxiv 513648; doi: https://doi.org/10.1101/513648
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts
Ari V. Ahola-Olli, Linda Mustelin, Maria Kalimeri, Johannes Kettunen, Jari Jokelainen, Juha Auvinen, Katri Puukka, Aki S. Havulinna, Terho Lehtimäki, Mika Kähönen, Markus Juonala, Sirkka Keinänen-Kiukaanniemi, Veikko Salomaa, Markus Perola, Marjo-Riitta Järvelin, Mika Ala-Korpela, Olli Raitakari, Peter Würtz
bioRxiv 513648; doi: https://doi.org/10.1101/513648

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Epidemiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4237)
  • Biochemistry (9153)
  • Bioengineering (6792)
  • Bioinformatics (24044)
  • Biophysics (12147)
  • Cancer Biology (9554)
  • Cell Biology (13811)
  • Clinical Trials (138)
  • Developmental Biology (7650)
  • Ecology (11724)
  • Epidemiology (2066)
  • Evolutionary Biology (15530)
  • Genetics (10660)
  • Genomics (14342)
  • Immunology (9499)
  • Microbiology (22872)
  • Molecular Biology (9113)
  • Neuroscience (49074)
  • Paleontology (357)
  • Pathology (1487)
  • Pharmacology and Toxicology (2573)
  • Physiology (3851)
  • Plant Biology (8343)
  • Scientific Communication and Education (1473)
  • Synthetic Biology (2299)
  • Systems Biology (6200)
  • Zoology (1302)