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dc.contributor.authorTuomisto, Karolina
dc.contributor.authorPalmu, Joonatan
dc.contributor.authorLong, Tao
dc.contributor.authorWatrous, Jeramie D
dc.contributor.authorMercader, Kysha
dc.contributor.authorLagerborg, Kim A
dc.contributor.authorAndres, Allen
dc.contributor.authorSalmi, Marko
dc.contributor.authorJalkanen, Sirpa
dc.contributor.authorVasan, Ramachandran S
dc.contributor.authorInouye, Michael
dc.contributor.authorHavulinna, Aki S
dc.contributor.authorTuomilehto, Jaakko
dc.contributor.authorJousilahti, Pekka
dc.contributor.authorNiiranen, Teemu J
dc.contributor.authorCheng, Susan
dc.contributor.authorJain, Mohit
dc.contributor.authorSalomaa, Veikko
dc.description.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.
dc.rightsAttribution-NonCommercial 4.0 International
dc.sourcenlmid: 101641391
dc.sourceessn: 2052-4897
dc.subjectDiabetes mellitus, type 2
dc.subjectDiabetes Mellitus, Type 2
dc.subjectRisk Factors
dc.subjectProspective Studies
dc.subjectMiddle Aged
dc.subjectMetabolic Syndrome
dc.titleA plasma metabolite score of three eicosanoids predicts incident type 2 diabetes: a prospective study in three independent cohorts.
prism.publicationNameBMJ open diabetes research & care
dc.contributor.orcidTuomisto, Karolina [0000-0002-1281-2749]
dc.contributor.orcidPalmu, Joonatan [0000-0003-0059-3347]
dc.contributor.orcidSalomaa, Veikko [0000-0001-7563-5324]
pubs.funder-project-idAcademy of Finland (321356, 46558, 321351, 141136)
pubs.funder-project-idDepartment of Medicine, Boston University School of Medicine (Evans Scholar award and Jay and Louis Coffman Foun)
pubs.funder-project-idFramingham Heart Study (N01-HC-25195, 75N92019D00031, HHSN268201500001I)
pubs.funder-project-idNHLBI NIH HHS (N01HC25195, HHSN268201500001I, 75N92019D00031, HHSN268201500001C)
pubs.funder-project-idNational Institutes of Health (S10OD020025, R01ES027595, K01DK116917)
pubs.funder-project-idFinnish Foundation for Cardiovascular Research (N/A)
pubs.funder-project-idFinnish Medical Foundation (N/A)
pubs.funder-project-idNIH HHS (S10 OD020025)
pubs.funder-project-idNIDDK NIH HHS (K01 DK116917)
pubs.funder-project-idEli Lilly Finland (N/A)
pubs.funder-project-idEmil Aaltonen Foundation (N/A)
pubs.funder-project-idThe Future Forum, Astra Zeneca (N/A)
pubs.funder-project-idPaavo Nurmi Foundation (N/A)
pubs.funder-project-idSocial Insurance Institution of Finland (N/A)
pubs.funder-project-idAarne Koskelo Foundation (N/A)
pubs.funder-project-idNIEHS NIH HHS (R01 ES027595)

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Attribution-NonCommercial 4.0 International
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