Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies

Jason H.Y. Wu; Matti Marklund; Fumiaki Imamura; Nathan Tintle; Andres V. Ardisson Korat; Janette de Goede; Xia Zhou; Wei Sin Yang; Marcia C. de Oliveira Otto; Janine Kröger; Waqas Qureshi; Jyrki K. Virtanen; Julie K. Bassett; Alexis C. Frazier-Wood; Maria Lankinen; Rachel A. Murphy; Kalina Rajaobelina; Liana C. Del Gobbo; Nita G. Forouhi; Robert Luben; Kay Tee Khaw; Nick Wareham; Anya Kalsbeek; Jenna Veenstra; Juhua Luo; Frank B. Hu; Hung Ju Lin; David S. Siscovick; Heiner Boeing; Tzu An Chen; Brian Steffen; Lyn M. Steffen; Allison Hodge; Gudny Eriksdottir; Albert V. Smith; Vilmunder Gudnason; Tamara B. Harris; Ingeborg A. Brouwer; Claudine Berr; Catherine Helmer; Cecilia Samieri; Markku Laakso; Michael Y. Tsai; Graham G. Giles; Tarja Nurmi; Lynne Wagenknecht; Matthias B. Schulze; Rozenn N. Lemaitre; Kuo Liong Chien; Sabita S. Soedamah-Muthu; Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)

doi:10.1016/S2213-8587(17)30307-8

Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies

Jason H.Y. Wu^*, Matti Marklund, Fumiaki Imamura, Nathan Tintle, Andres V. Ardisson Korat, Janette de Goede, Xia Zhou, Wei Sin Yang, Marcia C. de Oliveira Otto, Janine Kröger, Waqas Qureshi, Jyrki K. Virtanen, Julie K. Bassett, Alexis C. Frazier-Wood, Maria Lankinen, Rachel A. Murphy, Kalina Rajaobelina, Liana C. Del Gobbo, Nita G. Forouhi, Robert LubenKay Tee Khaw, Nick Wareham, Anya Kalsbeek, Jenna Veenstra, Juhua Luo, Frank B. Hu, Hung Ju Lin, David S. Siscovick, Heiner Boeing, Tzu An Chen, Brian Steffen, Lyn M. Steffen, Allison Hodge, Gudny Eriksdottir, Albert V. Smith, Vilmunder Gudnason, Tamara B. Harris, Ingeborg A. Brouwer, Claudine Berr, Catherine Helmer, Cecilia Samieri, Markku Laakso, Michael Y. Tsai, Graham G. Giles, Tarja Nurmi, Lynne Wagenknecht, Matthias B. Schulze, Rozenn N. Lemaitre, Kuo Liong Chien, Sabita S. Soedamah-Muthu, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)

^*Corresponding author for this work

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Abstract

Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings Participants were 39 740 adults, aged (range of cohort means) 49–76 years with a BMI (range of cohort means) of 23·3–28·4 kg/m², who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60–0·72, p<0·0001; I²=53·9%, p_{heterogeneity}=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88–1·05; p=0·38; I²=63·0%, p_{heterogeneity}<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all p_{heterogeneity}≥0·13). Interpretation Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. Funding Funders are shown in the appendix.

Original language	English
Pages (from-to)	965-974
Number of pages	10
Journal	The Lancet Diabetes and Endocrinology
Volume	5
Issue number	12
Early online date	12 Oct 2017
DOIs	https://doi.org/10.1016/S2213-8587(17)30307-8
Publication status	Published - Dec 2017

Funding

JHYW received research grants from Unilever for this study. LCDG received ad-hoc consulting fees from the Life Sciences Research Organization. CH received fees for a conference from Novartis. JMG received funding from Unilever for epidemiological studies of dietary and circulating fatty acids and cardiometabolic disease. RM received research grants from Unilever for this study. DM received ad-hoc honoraria and consulting fees from the Life Sciences Research Organization, AstraZeneca, Boston Heart Diagnostics, Global Organization for EPA and DHA Omega-3, DSM, Nutrition Impact, the Haas Avocado Board, and Pollock Communications; and chapter royalties from UpToDate. All other authors declare no competing interests.

Funders	Funder number
National Human Genome Research Institute	R15HG006915
Unilever

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Wu, J. H. Y., Marklund, M., Imamura, F., Tintle, N., Ardisson Korat, A. V., de Goede, J., Zhou, X., Yang, W. S., de Oliveira Otto, M. C., Kröger, J., Qureshi, W., Virtanen, J. K., Bassett, J. K., Frazier-Wood, A. C., Lankinen, M., Murphy, R. A., Rajaobelina, K., Del Gobbo, L. C., Forouhi, N. G., ... Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE) (2017). Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies. The Lancet Diabetes and Endocrinology, 5(12), 965-974. https://doi.org/10.1016/S2213-8587(17)30307-8

@article{9d69d09083a546b69a1bf135cafb6c74,

title = "Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies",

abstract = "Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings Participants were 39 740 adults, aged (range of cohort means) 49–76 years with a BMI (range of cohort means) of 23·3–28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60–0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88–1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13). Interpretation Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. Funding Funders are shown in the appendix.",

author = "Wu, {Jason H.Y.} and Matti Marklund and Fumiaki Imamura and Nathan Tintle and {Ardisson Korat}, {Andres V.} and {de Goede}, Janette and Xia Zhou and Yang, {Wei Sin} and {de Oliveira Otto}, {Marcia C.} and Janine Kr{\"o}ger and Waqas Qureshi and Virtanen, {Jyrki K.} and Bassett, {Julie K.} and Frazier-Wood, {Alexis C.} and Maria Lankinen and Murphy, {Rachel A.} and Kalina Rajaobelina and {Del Gobbo}, {Liana C.} and Forouhi, {Nita G.} and Robert Luben and Khaw, {Kay Tee} and Nick Wareham and Anya Kalsbeek and Jenna Veenstra and Juhua Luo and Hu, {Frank B.} and Lin, {Hung Ju} and Siscovick, {David S.} and Heiner Boeing and Chen, {Tzu An} and Brian Steffen and Steffen, {Lyn M.} and Allison Hodge and Gudny Eriksdottir and Smith, {Albert V.} and Vilmunder Gudnason and Harris, {Tamara B.} and Brouwer, {Ingeborg A.} and Claudine Berr and Catherine Helmer and Cecilia Samieri and Markku Laakso and Tsai, {Michael Y.} and Giles, {Graham G.} and Tarja Nurmi and Lynne Wagenknecht and Schulze, {Matthias B.} and Lemaitre, {Rozenn N.} and Chien, {Kuo Liong} and Soedamah-Muthu, {Sabita S.} and {Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)}",

year = "2017",

month = dec,

doi = "10.1016/S2213-8587(17)30307-8",

language = "English",

volume = "5",

pages = "965--974",

journal = "The Lancet Diabetes and Endocrinology",

issn = "2213-8587",

publisher = "Elsevier Ltd",

number = "12",

}

Wu, JHY, Marklund, M, Imamura, F, Tintle, N, Ardisson Korat, AV, de Goede, J, Zhou, X, Yang, WS, de Oliveira Otto, MC, Kröger, J, Qureshi, W, Virtanen, JK, Bassett, JK, Frazier-Wood, AC, Lankinen, M, Murphy, RA, Rajaobelina, K, Del Gobbo, LC, Forouhi, NG, Luben, R, Khaw, KT, Wareham, N, Kalsbeek, A, Veenstra, J, Luo, J, Hu, FB, Lin, HJ, Siscovick, DS, Boeing, H, Chen, TA, Steffen, B, Steffen, LM, Hodge, A, Eriksdottir, G, Smith, AV, Gudnason, V, Harris, TB, Brouwer, IA, Berr, C, Helmer, C, Samieri, C, Laakso, M, Tsai, MY, Giles, GG, Nurmi, T, Wagenknecht, L, Schulze, MB, Lemaitre, RN, Chien, KL, Soedamah-Muthu, SS & Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE) 2017, 'Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies', The Lancet Diabetes and Endocrinology, vol. 5, no. 12, pp. 965-974. https://doi.org/10.1016/S2213-8587(17)30307-8

Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies. / Wu, Jason H.Y.; Marklund, Matti; Imamura, Fumiaki et al.
In: The Lancet Diabetes and Endocrinology, Vol. 5, No. 12, 12.2017, p. 965-974.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies

AU - Wu, Jason H.Y.

AU - Marklund, Matti

AU - Imamura, Fumiaki

AU - Tintle, Nathan

AU - Ardisson Korat, Andres V.

AU - de Goede, Janette

AU - Zhou, Xia

AU - Yang, Wei Sin

AU - de Oliveira Otto, Marcia C.

AU - Kröger, Janine

AU - Qureshi, Waqas

AU - Virtanen, Jyrki K.

AU - Bassett, Julie K.

AU - Frazier-Wood, Alexis C.

AU - Lankinen, Maria

AU - Murphy, Rachel A.

AU - Rajaobelina, Kalina

AU - Del Gobbo, Liana C.

AU - Forouhi, Nita G.

AU - Luben, Robert

AU - Khaw, Kay Tee

AU - Wareham, Nick

AU - Kalsbeek, Anya

AU - Veenstra, Jenna

AU - Luo, Juhua

AU - Hu, Frank B.

AU - Lin, Hung Ju

AU - Siscovick, David S.

AU - Boeing, Heiner

AU - Chen, Tzu An

AU - Steffen, Brian

AU - Steffen, Lyn M.

AU - Hodge, Allison

AU - Eriksdottir, Gudny

AU - Smith, Albert V.

AU - Gudnason, Vilmunder

AU - Harris, Tamara B.

AU - Brouwer, Ingeborg A.

AU - Berr, Claudine

AU - Helmer, Catherine

AU - Samieri, Cecilia

AU - Laakso, Markku

AU - Tsai, Michael Y.

AU - Giles, Graham G.

AU - Nurmi, Tarja

AU - Wagenknecht, Lynne

AU - Schulze, Matthias B.

AU - Lemaitre, Rozenn N.

AU - Chien, Kuo Liong

AU - Soedamah-Muthu, Sabita S.

AU - Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)

PY - 2017/12

Y1 - 2017/12

N2 - Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings Participants were 39 740 adults, aged (range of cohort means) 49–76 years with a BMI (range of cohort means) of 23·3–28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60–0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88–1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13). Interpretation Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. Funding Funders are shown in the appendix.

AB - Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings Participants were 39 740 adults, aged (range of cohort means) 49–76 years with a BMI (range of cohort means) of 23·3–28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60–0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88–1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13). Interpretation Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. Funding Funders are shown in the appendix.

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