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 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 H.Y. Wu; Amanda Fretts; Rozenn N. Lemaitre; Renata Micha; Dariush Mozaffarian; Qi Sun

doi:10.2337/dc20-2426

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

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Abstract

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 language	English (US)
Pages (from-to)	1133-1142
Number of pages	10
Journal	Diabetes care
Volume	44
Issue number	5
DOIs	https://doi.org/10.2337/dc20-2426
State	Published - May 1 2021

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Publisher Copyright:
© 2021 by the American Diabetes Association.

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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., ... 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, 44(5), 1133-1142. https://doi.org/10.2337/dc20-2426

Qian, F, Ardisson Korat, AV, Imamura, F, Marklund, M, Tintle, N, Virtanen, JK, Zhou, X, Bassett, JK, Lai, H, Hirakawa, Y, Chien, KL, Wood, AC, Lankinen, M, Murphy, RA, Samieri, C, Pertiwi, K, de Mello, VD, Guan, W, Forouhi, NG, Wareham, N, Consortium, I, Hu, FB, Riserus, U, Lind, L, Harris, WS, Shadyab, AH, Robinson, JG, Steffen, LM, Hodge, A, Giles, GG, Ninomiya, T, Uusitupa, M, Tuomilehto, J, Lindström, J, Laakso, M, Siscovick, DS, Helmer, C, Geleijnse, JM, Wu, JHY, Fretts, A, Lemaitre, RN, 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, vol. 44, no. 5, pp. 1133-1142. https://doi.org/10.2337/dc20-2426

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

abstract = "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.",

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

note = "Publisher Copyright: {\textcopyright} 2021 by the American Diabetes Association.",

year = "2021",

month = may,

day = "1",

doi = "10.2337/dc20-2426",

language = "English (US)",

volume = "44",

pages = "1133--1142",

journal = "Diabetes care",

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TY - JOUR

T1 - N-3 fatty acid biomarkers and incident type 2 diabetes

T2 - An individual participant-level pooling project of 20 prospective cohort studies

AU - Qian, Frank

AU - Ardisson Korat, Andres V.

AU - Imamura, Fumiaki

AU - Marklund, Matti

AU - Tintle, Nathan

AU - Virtanen, Jyrki K.

AU - Zhou, Xia

AU - Bassett, Julie K.

AU - Lai, Heidi

AU - Hirakawa, Yoichiro

AU - Chien, Kuo Liong

AU - Wood, Alexis C.

AU - Lankinen, Maria

AU - Murphy, Rachel A.

AU - Samieri, Cecilia

AU - Pertiwi, Kamalita

AU - de Mello, Vanessa D.

AU - Guan, Weihua

AU - Forouhi, Nita G.

AU - Wareham, Nick

AU - Consortium, Interact

AU - Hu, Frank B.

AU - Riserus, Ulf

AU - Lind, Lars

AU - Harris, William S.

AU - Shadyab, Aladdin H.

AU - Robinson, Jennifer G.

AU - Steffen, Lyn M.

AU - Hodge, Allison

AU - Giles, Graham G.

AU - Ninomiya, Toshiharu

AU - Uusitupa, Matti

AU - Tuomilehto, Jaakko

AU - Lindström, Jaana

AU - Laakso, Markku

AU - Siscovick, David S.

AU - Helmer, Catherine

AU - Geleijnse, Johanna M.

AU - Wu, Jason H.Y.

AU - Fretts, Amanda

AU - Lemaitre, Rozenn N.

AU - Micha, Renata

AU - Mozaffarian, Dariush

AU - Sun, Qi

PY - 2021/5/1

Y1 - 2021/5/1

N2 - 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.

AB - 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.

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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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