N-3 fatty acid biomarkers and incident type 2 diabetes: An individual participant-level pooling project of 20 prospective cohort studies

Frank Qian, Andres V. Ardisson Korat, Fumiaki Imamura, Matti Marklund, Nathan Tintle, Jyrki K. Virtanen, Xia Zhou, Julie K. Bassett, Heidi Lai, Yoichiro Hirakawa, Kuo Liong Chien, Alexis C. Wood, Maria Lankinen, Rachel A. Murphy, Cecilia Samieri, Kamalita Pertiwi, Vanessa D. de Mello, Weihua Guan, Nita G. Forouhi, Nick WarehamInteract Consortium, Frank B. Hu, Ulf Riserus, Lars Lind, William S. Harris, Aladdin H. Shadyab, Jennifer G. Robinson, Lyn M. Steffen, Allison Hodge, Graham G. Giles, Toshiharu Ninomiya, Matti Uusitupa, Jaakko Tuomilehto, Jaana Lindström, Markku Laakso, David S. Siscovick, Catherine Helmer, Johanna M. Geleijnse, Jason H.Y. Wu, Amanda Fretts, Rozenn N. Lemaitre, Renata Micha, Dariush Mozaffarian, Qi Sun

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


OBJECTIVE: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

RESEARCH DESIGN AND METHODS: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.

RESULTS: A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.

CONCLUSIONS: Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.

Original languageEnglish (US)
Pages (from-to)1133-1142
Number of pages10
JournalDiabetes care
Issue number5
StatePublished - May 1 2021

Bibliographical note

Funding Information:
Funding. Funding for this work was supported by National Heart, Lung, and Blood Institute, National Institutes of Health, research grants R01HL034594 and R01HL088521 and by research grants U01CA167552 and R01HL35464 from the National Institutes of Health. Funding for individual cohorts is listed in the Supplementary Appendix. D.M. reports (all outside the submitted work) research funding from the National Institutes of Health and the Bill &Melinda Gates Foundation and personal fees from the Cleveland Clinic Foundation. DualityofInterest.W.S.H.holdsstockinOmega-Quant Analytics, LLC, and is a member of the RB Schiff Science and Innovation Advisory Board. D.M. reports (all outside the submitted work) personal fees from GOED, Nutrition Impact, Bunge, Indigo Agriculture, Motif FoodWorks, Amarin, Acasti Pharma, America’s Test Kitchen, and Danone; serving on the scientific advisory board for Brightseed, DayTwo, Elysium Health, Filtricine, HumanCo, and Tiny Organics; and chapter royalties from UpToDate. No other potential conflicts of interest relevant to this article were reported. Author Contributions. All authors contributed to the study conception and design. F.Q., A.V.A.K., F.I., M.M., N.T., X.Z., J.K.B., H.L., Y.H., K.-L.C., A.C.W., M.L., R.A.M., C.S., J.M.G., V.D.d.M., and W.G. conducted the data analysis. All authors interpreted the data. F.Q., A.V.A.K., F.I., N.G.F., J.H.Y.W., R.N.L., R.M., D.M., and Q.S. wrote the first draft of the article. All authors reviewed and edited the manuscript and approved the final version for submission. F.Q. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract form at the American Heart Association EPI|Lifestyle 2019 Scientific Sessions, Houston, TX, 5–8 March 2019.

Publisher Copyright:
© 2021 by the American Diabetes Association.


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