A plasma metabolite score of three eicosanoids predicts incident type 2 diabetes: a prospective study in three independent cohorts.
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Authors
Long, Tao
Watrous, Jeramie D
Mercader, Kysha
Lagerborg, Kim A
Andres, Allen
Salmi, Marko
Jalkanen, Sirpa
Vasan, Ramachandran S
Inouye, Michael
Havulinna, Aki S
Tuomilehto, Jaakko
Jousilahti, Pekka
Niiranen, Teemu J
Cheng, Susan
Jain, Mohit
Publication Date
2022-03-01Journal Title
BMJ open diabetes research & care
ISSN
2052-4897
Volume
10
Issue
2
Language
eng
Type
Article
This Version
VoR
Metadata
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Tuomisto, K., Palmu, J., Long, T., Watrous, J. D., Mercader, K., Lagerborg, K. A., Andres, A., et al. (2022). A plasma metabolite score of three eicosanoids predicts incident type 2 diabetes: a prospective study in three independent cohorts.. BMJ open diabetes research & care, 10 (2) https://doi.org/10.1136/bmjdrc-2021-002519
Abstract
<h4>Introduction</h4>Peptide markers of inflammation have been associated with the development of type 2 diabetes. The role of upstream, lipid-derived mediators of inflammation such as eicosanoids, remains less clear. The aim of this study was to examine whether eicosanoids are associated with incident type 2 diabetes.<h4>Research design & methods</h4>In the FINRISK (Finnish Cardiovascular Risk Study) 2002 study, a population-based sample of Finnish men and women aged 25-74 years, we used directed, non-targeted liquid chromatography-mass spectrometry to identify 545 eicosanoids and related oxylipins in the participants' plasma samples (n=8292). We used multivariable-adjusted Cox regression to examine associations between eicosanoids and incident type 2 diabetes. The significant independent findings were replicated in the Framingham Heart Study (FHS, n=2886) and DIetary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) 2007 (n=3905). Together, these three cohorts had 1070 cases of incident type 2 diabetes.<h4>Results</h4>In the FINRISK 2002 cohort, 76 eicosanoids were associated individually with incident type 2 diabetes. We identified three eicosanoids independently associated with incident type 2 diabetes using stepwise Cox regression with forward selection and a Bonferroni-corrected inclusion threshold. A three-eicosanoid risk score produced an HR of 1.56 (95% CI 1.41 to 1.72) per 1 SD increment for risk of incident diabetes. The HR for comparing the top quartile with the lowest was 2.80 (95% CI 2.53 to 3.07). In the replication analyses, the three-eicosanoid risk score was significant in FHS (HR 1.24 (95% CI 1.10 to 1.39, p<0.001)) and directionally consistent in DILGOM (HR 1.12 (95% CI 0.99 to 1.27, p=0.07)). Meta-analysis of the three cohorts yielded a pooled HR of 1.31 (95% CI 1.05 to 1.56).<h4>Conclusions</h4>Plasma eicosanoid profiles predict incident type 2 diabetes and the clearest signals replicate in three independent cohorts. Our findings give new information on the biology underlying type 2 diabetes and suggest opportunities for early identification of people at risk.
Keywords
Inflammation, Diabetes mellitus, type 2, epidemiology, Eicosanoids, Humans, Diabetes Mellitus, Type 2, Risk Factors, Prospective Studies, Adult, Aged, Middle Aged, Female, Male, Metabolic Syndrome
Sponsorship
Academy of Finland (321356, 46558, 321351, 141136)
Department of Medicine, Boston University School of Medicine (Evans Scholar award and Jay and Louis Coffman Foun)
Framingham Heart Study (N01-HC-25195, 75N92019D00031, HHSN268201500001I)
NHLBI NIH HHS (N01HC25195, HHSN268201500001I, 75N92019D00031, HHSN268201500001C)
National Institutes of Health (S10OD020025, R01ES027595, K01DK116917)
Finnish Foundation for Cardiovascular Research (N/A)
Finnish Medical Foundation (N/A)
NIH HHS (S10 OD020025)
NIDDK NIH HHS (K01 DK116917)
Eli Lilly Finland (N/A)
Emil Aaltonen Foundation (N/A)
The Future Forum, Astra Zeneca (N/A)
Paavo Nurmi Foundation (N/A)
Social Insurance Institution of Finland (N/A)
Aarne Koskelo Foundation (N/A)
NIEHS NIH HHS (R01 ES027595)
Identifiers
35361620, PMC8971778
External DOI: https://doi.org/10.1136/bmjdrc-2021-002519
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336821
Rights
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/
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