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

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Circulating metabolites and the risk of type 2 diabetes : a prospective study of 11,896 young adults from four Finnish cohorts. / Ahola-Olli, Ari V.; Mustelin, Linda; Kalimeri, Maria; Kettunen, Johannes; Jokelainen, Jari; Auvinen, Juha; Puukka, Katri; Havulinna, Aki S.; Lehtimäki, Terho; Kähönen, Mika; Juonala, Markus; Keinänen-Kiukaanniemi, Sirkka; Salomaa, Veikko; Perola, Markus; Järvelin, Marjo Riitta; Ala-Korpela, Mika; Raitakari, Olli; Würtz, Peter.

In: Diabetologia, Vol. 62, No. 12, 01.12.2019, p. 2298-2309.

Research output: Contribution to journalArticle

Harvard

Ahola-Olli, AV, Mustelin, L, Kalimeri, M, Kettunen, J, Jokelainen, J, Auvinen, J, Puukka, K, Havulinna, AS, Lehtimäki, T, Kähönen, M, Juonala, M, Keinänen-Kiukaanniemi, S, Salomaa, V, Perola, M, Järvelin, MR, Ala-Korpela, M, Raitakari, O & Würtz, P 2019, 'Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts', Diabetologia, vol. 62, no. 12, pp. 2298-2309. https://doi.org/10.1007/s00125-019-05001-w

APA

Ahola-Olli, A. V., Mustelin, L., Kalimeri, M., Kettunen, J., Jokelainen, J., Auvinen, J., ... Würtz, P. (2019). Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts. Diabetologia, 62(12), 2298-2309. https://doi.org/10.1007/s00125-019-05001-w

Vancouver

Ahola-Olli AV, Mustelin L, Kalimeri M, Kettunen J, Jokelainen J, Auvinen J et al. Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts. Diabetologia. 2019 Dec 1;62(12):2298-2309. https://doi.org/10.1007/s00125-019-05001-w

Author

Ahola-Olli, Ari V. ; Mustelin, Linda ; Kalimeri, Maria ; Kettunen, Johannes ; Jokelainen, Jari ; Auvinen, Juha ; Puukka, Katri ; Havulinna, Aki S. ; Lehtimäki, Terho ; Kähönen, Mika ; Juonala, Markus ; Keinänen-Kiukaanniemi, Sirkka ; Salomaa, Veikko ; Perola, Markus ; Järvelin, Marjo Riitta ; Ala-Korpela, Mika ; Raitakari, Olli ; Würtz, Peter. / Circulating metabolites and the risk of type 2 diabetes : a prospective study of 11,896 young adults from four Finnish cohorts. In: Diabetologia. 2019 ; Vol. 62, No. 12. pp. 2298-2309.

Bibtex

@article{016d3b5e43314f568df2527e2432ab5f,
title = "Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts",
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.",
keywords = "Branched-chain amino acid, Isoleucine, Leucine, Metabolomics, Type 2 diabetes",
author = "Ahola-Olli, {Ari V.} and Linda Mustelin and Maria Kalimeri and Johannes Kettunen and Jari Jokelainen and Juha Auvinen and Katri Puukka and Havulinna, {Aki S.} and Terho Lehtim{\"a}ki and Mika K{\"a}h{\"o}nen and Markus Juonala and Sirkka Kein{\"a}nen-Kiukaanniemi and Veikko Salomaa and Markus Perola and J{\"a}rvelin, {Marjo Riitta} and Mika Ala-Korpela and Olli Raitakari and Peter W{\"u}rtz",
year = "2019",
month = "12",
day = "1",
doi = "10.1007/s00125-019-05001-w",
language = "English",
volume = "62",
pages = "2298--2309",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Berlin Heidelberg",
number = "12",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Circulating metabolites and the risk of type 2 diabetes

T2 - a prospective study of 11,896 young adults from four Finnish cohorts

AU - Ahola-Olli, Ari V.

AU - Mustelin, Linda

AU - Kalimeri, Maria

AU - Kettunen, Johannes

AU - Jokelainen, Jari

AU - Auvinen, Juha

AU - Puukka, Katri

AU - Havulinna, Aki S.

AU - Lehtimäki, Terho

AU - Kähönen, Mika

AU - Juonala, Markus

AU - Keinänen-Kiukaanniemi, Sirkka

AU - Salomaa, Veikko

AU - Perola, Markus

AU - Järvelin, Marjo Riitta

AU - Ala-Korpela, Mika

AU - Raitakari, Olli

AU - Würtz, Peter

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

KW - Branched-chain amino acid

KW - Isoleucine

KW - Leucine

KW - Metabolomics

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85073951970&partnerID=8YFLogxK

U2 - 10.1007/s00125-019-05001-w

DO - 10.1007/s00125-019-05001-w

M3 - Article

C2 - 31584131

VL - 62

SP - 2298

EP - 2309

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 12

ER -