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

40 Citations (Scopus)


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 a-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 Highercirculating biomarkers of seafood-derivedn-3 fattyacids, 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
Pages (from-to)1133-1142
Number of pages10
JournalDiabetes care
Issue number5
Publication statusPublished - May 1 2021

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing


Dive into the research topics of 'N-3 fatty acid biomarkers and incident type 2 diabetes: An individual participant-level pooling project of 20 prospective cohort studies'. Together they form a unique fingerprint.

Cite this