Version 2 2021-03-09, 15:48Version 2 2021-03-09, 15:48
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posted on 2021-03-09, 15:48authored byFrank 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)
<b><i>Objective</i></b><b> </b>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.
<p><b><i>Research
Design and Methods </i></b>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.</p>
<p><i>De novo</i>
harmonized analyses were performed in each cohort following a pre-specified
protocol and cohort-specific associations were pooled using inverse
variance-weighted meta-analysis.</p>
<p><b><i>Results</i></b><b> </b>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 90<sup>th</sup>
and 10<sup>th</sup> 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 <i>P</i><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. </p>
<p><b><i>Conclusions </i></b><a></a><a>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. </a>The
biomarker of plant-derived ALA was not significantly associated with T2D risk. </p>
Funding
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.