A plasma metabolite score of three eicosanoids predicts incident type 2 diabetes: a prospective study in three independent cohorts

Karolina Tuomisto, Joonatan Palmu, Tao Long, Jeramie D. Watrous, Kysha Mercader, Kim A. Lagerborg, Allen Andres, Marko Salmi, Sirpa Jalkanen, Ramachandran S. Vasan, Michael Inouye, Aki S. Havulinna, Jaakko Tuomilehto, Pekka Jousilahti, Teemu J. Niiranen, Susan Cheng, Mohit Jain, Veikko Salomaa

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Introduction 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. Research design & methods 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. Results 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). Conclusions 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.

Idioma originalEnglish (US)
Número de artículoe002519
PublicaciónBMJ Open Diabetes Research and Care
EstadoPublished - mar 31 2022
Publicado de forma externa

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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