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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-10-04

AUTHORS

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

ABSTRACT

Aims/hypothesisMetabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case−control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults.MethodsNMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24–45 years). Associations between baseline metabolites and risk of developing diabetes during 8–15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up.ResultsOut of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59–1.50; p< 0.0009). Among the strongest biomarkers of diabetes risk were branched-chain and aromatic amino acids (OR 1.31–1.33) and triacylglycerol within VLDL particles (OR 1.33–1.50), as well as linoleic n-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years).Conclusions/interpretationMetabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk. More... »

PAGES

2298-2309

Journal

TITLE

Diabetologia

ISSUE

12

VOLUME

62

Author Affiliations

  • Institute for Molecular Medicine (FIMM), University of Helsinki, Tukholmankatu 8, 00014, Helsinki, Finland
  • Department of Public Health, University of Helsinki, Helsinki, Finland
  • Nightingale Health Ltd, Mannerheimintie 164a, 00300, Helsinki, Finland
  • NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
  • Unit of Primary Health Care and Medical Research Center, Oulu University Hospital, Oulu, Finland
  • Oulunkaari Primary Health Care Unit, Ii, Finland
  • Department of Clinical Chemistry, University of Oulu, Oulu, Finland
  • National Institute for Health and Welfare, Helsinki, Finland
  • Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  • Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
  • Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland
  • Diabetes Unit, Healthcare Services of City of Oulu, Oulu, Finland
  • Estonian Genome Center, University of Tartu, Tartu, Estonia
  • Department of Life Sciences, College of Health and Life Sciences, Brunel University, London, UK
  • Department 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, Victoria, Australia
  • Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
  • Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00125-019-05001-w

    DOI

    http://dx.doi.org/10.1007/s00125-019-05001-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1121496474

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31584131


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