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Open Access 01-12-2019 | Insulins | Article

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

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

Published in: Diabetologia | Issue 12/2019

Abstract

Aims/hypothesis

Metabolomics 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.

Methods

NMR 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.

Results

Out 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/interpretation

Metabolic 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.

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Title: Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts
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
Publication date: 01-12-2019
Publisher: Springer Berlin Heidelberg
Keywords: Insulins
Insulins
Type 2 Diabetes
Biomarkers
Published in: Diabetologia / Issue 12/2019
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-019-05001-w

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