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

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.

• Authors: 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
• Journal: BMJ open diabetes research & care (BMJ Open Diabetes Res Care) Vol. 10 Issue 2 (03 2022) ISSN: 2052-4897 [Electronic] England
• PMID: 35361620 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Eicosanoids

Topics

• Adult
• Aged
• Diabetes Mellitus, Type 2 (complications)
• Eicosanoids
• Female
• Humans
• Male
• Metabolic Syndrome
• Middle Aged
• Prospective Studies
• Risk Factors