American Diabetes Association
FORCE N-3 T2D Supplementary Appendix v8.pdf (1.26 MB)

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies

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Version 2 2021-03-09, 15:48
Version 1 2021-03-04, 00:31
posted on 2021-03-09, 15:48 authored by 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 Wareham, InterAct 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 HY Wu, Amanda Fretts, Rozenn N Lemaitre, Renata Micha, Dariush Mozaffarian, Qi Sun, the Fatty Acids and Outcomes Research Consortium (FORCE)
Objective Prospective associations between omega-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize prospective associations between biomarkers of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), and T2D risk through an individual participant-level pooled analysis.

Research Design and Methods Our analysis 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 pre-specified 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 inter-quintile 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% confidence intervals (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, 0.97 (0.92, 1.02) per inter-quintile range. Associations were robust across pre-specified subgroups as well as in sensitivity analyses.

Conclusions Higher circulating biomarkers of seafood-derived omega-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.


Funding for this work was supported by research grants R01HL034594, R01HL088521, U01CA167552, and R01HL35464 from the National Institutes of Health. Funding for individual cohorts are listed in the Supplementary Appendix.


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