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

Authors: QIAN, FRANK - Harvard School Of Public Health; ARDISSON KORAT, ANDRES - Harvard School Of Public Health; IMAMURA, FUMIAKI - University Of Cambridge; MARKLUND, MATTI - Uppsala University; TINTLE, NATHAN - Dordt College; VIRTANEN, JYRKI - University Of Eastern Finland; ZHOU, XIA - University Of Minnesota; BASSETT, JULIE - Cancer Council Victoria; LAI, HEIDI - Uppsala University; HIRAKAWA, YOICHIRO - Kyushu University; CHIEN, KUO - National Taiwan University; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); LANKINEN, MARIA - University Of Eastern Finland; MURPHY, RACHEL - University Of British Columbia; SAMIERI, CECILIA - University Of Bordeaux; PERTIWI, KAMALITA - Wageningen University; DE MELLO, VANESSA - University Of Eastern Finland; GUAN, WEIHUA - University Of Minnesota; FOROUHI, NITA - University Of Cambridge; WAREHAM, NICK - University Of Cambridge; HU, FRANK - Harvard School Of Public Health; RISERUS, ULF - Uppsala University; LIND, LARS - Uppsala University; HARRIS, WILLIAM - University Of South Dakota; SHADYAB, ALADDIN - University Of California, San Diego; ROBINSON, JENNIFER - University Of Iowa; STEFFEN, LYN - University Of Eastern Finland; HODGE, ALLISON - University Of Minnesota; GILES, GRAHAM - University Of Minnesota; NINOMIYA, TOSHIHARU - Kyushu University; UUSITUPA, MATTI - Fatty Acid Research Institute; TUOMILEHTO, JAAKKO - Finnish Institute For Health And Welfare; LINDSTRÖM, JAANA - Finnish Institute For Health And Welfare; LAAKSO, MARKKU - University Of Eastern Finland; SISCOVICK, DAVID - New York Academy Of Medicine; HELMER, CATHERINE - University Of British Columbia; GELEIJNSE, JOHANNA - University Of Bordeaux; WU, JASON - University Of New South Wales; FRETTS, AMANDA - University Of Washington; LEMAITRE, ROZENN - University Of Washington; MICHA, RENATA - Friedman School At Tufts; MOZAFFARIAN, DARIUSH - Friedman School At Tufts; SUN, QI - Harvard School Of Public Health

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/4/2021
Publication Date: 3/3/2021
Citation: Qian, F., Ardisson Korat, A.V., Imamura, F., Marklund, M., Tintle, N., Virtanen, J.K., Zhou, X., Bassett, J.K., Lai, H., Hirakawa, Y., Chien, K.L., Wood, A.C., Lankinen, M., Murphy, R.A., Samieri, C., Pertiwi, K., de Mello, V.D., Guan, W., Forouhi, N.G., Wareham, N., Hu, F.B., Riserus, U., Lind, L., Harris, W.S., Shadyab, A.H., Robinson, J.G., Steffen, L.M., Hodge, A., Giles, G.G., Ninomiya, T., Uusitupa, M., Tuomilehto, J., Lindström, J., Laakso, M., Siscovick, D.S., Helmer, C., Geleijnse, J.M., Wu, J.H., Fretts, A., Lemaitre, R.N., Micha, R., Mozaffarian, D., Sun, Q. 2021. n-3 fatty acid biomarkers and incident type 2 diabetes: An individual participant-level pooling project of 20 prospective cohort studies. Diabetes Care. https://doi.org/10.2337/dc20-2426.
DOI: https://doi.org/10.2337/dc20-2426

Interpretive Summary: It has been suggested that consuming omega-3, a type of fatty acid, in the diet reduces the risk of type 2 diabetes. However, studies do not consistently report this – some find no protection associated with consuming omega-3. Most studies investigating this potential association are limited by methodological problems such as self-reported dietary intake, or the possibility that people changed their diet after a diagnosis of type 2 diabetes. Therefore, it is still not known if omega-3 fatty acids may help protect against type 2 diabetes. To help researchers, clinicians and policy makers better understand the link between omega-3 and type 2 diabetes, we conducted a very large-scale investigation on over 65,000 individuals, across time. We also measured the levels of four different omega-3 fatty acids in the blood, rather than relying on self-reported intake data. We found that levels of three out of the four omega-3 fatty acids in the blood were associated with a reduced risk of type 2 diabetes, while the other fatty acid examined was not associated with type 2 diabetes. Since the omega-3 fatty acids examined in this study can be derived from seafood, these analyses might help guide the dietary choices of individuals seeking to reduce their risk of type 2 diabetes.

Technical Abstract: 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 alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis. 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. 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. 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.