TY - JOUR
T1 - A plasma metabolite score of three eicosanoids predicts incident type 2 diabetes
T2 - a prospective study in three independent cohorts
AU - Tuomisto, Karolina
AU - Palmu, Joonatan
AU - Long, Tao
AU - Watrous, Jeramie D.
AU - Mercader, Kysha
AU - Lagerborg, Kim A.
AU - Andres, Allen
AU - Salmi, Marko
AU - Jalkanen, Sirpa
AU - Vasan, Ramachandran S.
AU - Inouye, Michael
AU - Havulinna, Aki S.
AU - Tuomilehto, Jaakko
AU - Jousilahti, Pekka
AU - Niiranen, Teemu J.
AU - Cheng, Susan
AU - Jain, Mohit
AU - Salomaa, Veikko
N1 - Funding Information:
Funding This work was supported by Paavo Nurmi, Aarne Koskelo, Emil Aaltonen and Finnish Medical Foundations, and Academy of Finland (#141136 to MS and SJ; #321356 to ASH; #321351 to TJN; #46558 to JT). VS was supported by the Finnish Foundation for Cardiovascular Research. MJ and JDW were supported by grants from the US National Institutes of Health, including NIH S10OD020025 and R01ES027595 to MJ and K01DK116917 to JDW. This work was partially supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (contracts N01-HC-25195, HHSN268201500001I and 75N92019D00031). RSV is supported by an Evans Scholar award and Jay and Louis Coffman Foundation from the Department of Medicine, Boston University School of Medicine. The glucose tolerance testing in this work was supported by the grants to JT from Academy of Finland (grant 46558); the Social Insurance Institution of Finland; the Future Forum, Astra Zeneca and Eli Lilly Finland.
Funding Information:
Competing interests VS has received honoraria for consulting from Novo Nordisk and Sanofi. He also has ongoing research collaboration with Bayer (all unrelated to the present study). JT has received research funding from Bayer and owns stocks of Orion Pharma and Aktivolabs. Other authors declare no conflicts of interest.
Publisher Copyright:
©
PY - 2022/3/31
Y1 - 2022/3/31
N2 - 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.
AB - 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.
KW - diabetes mellitus, type 2
KW - eicosanoids
KW - epidemiology
KW - inflammation
UR - http://www.scopus.com/inward/record.url?scp=85127385233&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85127385233&partnerID=8YFLogxK
U2 - 10.1136/bmjdrc-2021-002519
DO - 10.1136/bmjdrc-2021-002519
M3 - Article
C2 - 35361620
AN - SCOPUS:85127385233
VL - 10
JO - BMJ Open Diabetes Research and Care
JF - BMJ Open Diabetes Research and Care
SN - 2052-4897
IS - 2
M1 - e002519
ER -