A plasma metabolite score of three eicosanoids predicts incident type 2 diabetes: a prospective study in three independent cohorts. Issue 2 (31st March 2022)

• Record Type: Journal Article
• Authors: Tuomisto, Karolina; Palmu, Joonatan; 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; Salomaa, Veikko
• Is Part Of: BMJ open diabetes research and care. Volume 10:Issue 2(2022)
• Publication Date: 2022-03-31
• Subjects: eicosanoids -- inflammation -- diabetes mellitus, type 2 -- epidemiology; Diabetes -- Periodicals; 616.462005
• DOI: 10.1136/bmjdrc-2021-002519
• Languages: English
• ISSNs: 2052-4897

Abstract

Abstract : 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.