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, Alexis C Frazier-wood, Julie K Bassett, Maria Lankinen, Rachel A Murphy, Kalina Rajaobelina, Liana C Del Gobbo, Nita G Forouhi, Robert Luben & 38 others 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, S.S. Soedamah-Muthu, Johanna M Geleijnse, Qi Sun, William S Harris, Lars Lind, Johan Ärnlöv, Ulf Riserus, Renata Micha, Dariush Mozaffarian

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
Pages (from-to)965-974
JournalLancet Diabetes Endocrinol
Volume5
Issue number12
DOIs
Publication statusPublished - 2017

Fingerprint

Omega-6 Fatty Acids
Type 2 Diabetes Mellitus
Linoleic Acid
Arachidonic Acid
Unsaturated Fatty Acids
Odds Ratio
Lipids
Iceland
Cholesterol Esters
Finland

Cite this

Wu, Jason H Y ; Marklund, Matti ; Imamura, Fumiaki ; Tintle, Nathan ; Ardisson Korat, Andres V ; De Goede, Janette ; Zhou, Xia ; Yang, Wei-sin ; De Oliveira Otto, Marcia C ; Kröger, Janine ; Qureshi, Waqas ; Virtanen, Jyrki K ; Frazier-wood, Alexis C ; Bassett, Julie K ; Lankinen, Maria ; Murphy, Rachel A ; Rajaobelina, Kalina ; Del Gobbo, Liana C ; Forouhi, Nita G ; Luben, Robert ; Khaw, Kay-tee ; Wareham, Nick ; Kalsbeek, Anya ; Veenstra, Jenna ; Luo, Juhua ; Hu, Frank B ; Lin, Hung-ju ; Siscovick, David S ; Boeing, Heiner ; Chen, Tzu-an ; Steffen, Brian ; Steffen, Lyn M ; Hodge, Allison ; Eriksdottir, Gudny ; Smith, Albert V ; Gudnason, Vilmunder ; Harris, Tamara B ; Brouwer, Ingeborg A ; Berr, Claudine ; Helmer, Catherine ; Samieri, Cecilia ; Laakso, Markku ; Tsai, Michael Y ; Giles, Graham G ; Nurmi, Tarja ; Wagenknecht, Lynne ; Schulze, Matthias B ; Lemaitre, Rozenn N ; Chien, Kuo-liong ; Soedamah-Muthu, S.S. ; Geleijnse, Johanna M ; Sun, Qi ; Harris, William S ; Lind, Lars ; Ärnlöv, Johan ; Riserus, Ulf ; Micha, Renata ; Mozaffarian, Dariush. / 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. In: Lancet Diabetes Endocrinol. 2017 ; Vol. 5, No. 12. pp. 965-974.
@article{e96191da8f4c43e8a1e2be8d825c1e88,
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 = "BackgroundThe 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.MethodsWe 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.FindingsParticipants 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).InterpretationFindings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.",
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 Wei-sin Yang and {De Oliveira Otto}, {Marcia C} and Janine Kr{\"o}ger and Waqas Qureshi and Virtanen, {Jyrki K} and Frazier-wood, {Alexis C} and Bassett, {Julie K} and Maria Lankinen and Murphy, {Rachel A} and Kalina Rajaobelina and {Del Gobbo}, {Liana C} and Forouhi, {Nita G} and Robert Luben and Kay-tee Khaw and Nick Wareham and Anya Kalsbeek and Jenna Veenstra and Juhua Luo and Hu, {Frank B} and Hung-ju Lin and Siscovick, {David S} and Heiner Boeing and Tzu-an Chen 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 Kuo-liong Chien and S.S. Soedamah-Muthu and Geleijnse, {Johanna M} and Qi Sun and Harris, {William S} and Lars Lind and Johan {\"A}rnl{\"o}v and Ulf Riserus and Renata Micha and Dariush Mozaffarian",
year = "2017",
doi = "10.1016/S2213-8587(17)30307-8",
language = "English",
volume = "5",
pages = "965--974",
journal = "Lancet Diabetes Endocrinol",
issn = "2213-8587",
publisher = "Elsevier BV",
number = "12",

}

Wu, JHY, Marklund, M, Imamura, F, Tintle, N, Ardisson Korat, AV, De Goede, J, Zhou, X, Yang, W, De Oliveira Otto, MC, Kröger, J, Qureshi, W, Virtanen, JK, Frazier-wood, AC, Bassett, JK, Lankinen, M, Murphy, RA, Rajaobelina, K, Del Gobbo, LC, Forouhi, NG, Luben, R, Khaw, K, Wareham, N, Kalsbeek, A, Veenstra, J, Luo, J, Hu, FB, Lin, H, Siscovick, DS, Boeing, H, Chen, T, 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, K, Soedamah-Muthu, SS, Geleijnse, JM, Sun, Q, Harris, WS, Lind, L, Ärnlöv, J, Riserus, U, Micha, R & Mozaffarian, D 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' Lancet Diabetes Endocrinol, 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; Tintle, Nathan; Ardisson Korat, Andres V; De Goede, Janette; Zhou, Xia; Yang, Wei-sin; De Oliveira Otto, Marcia C; Kröger, Janine; Qureshi, Waqas; Virtanen, Jyrki K; Frazier-wood, Alexis C; Bassett, Julie K; Lankinen, Maria; Murphy, Rachel A; Rajaobelina, Kalina; Del Gobbo, Liana C; Forouhi, Nita G; Luben, Robert; Khaw, Kay-tee; Wareham, Nick; Kalsbeek, Anya; Veenstra, Jenna; Luo, Juhua; Hu, Frank B; Lin, Hung-ju; Siscovick, David S; Boeing, Heiner; Chen, Tzu-an; Steffen, Brian; Steffen, Lyn M; Hodge, Allison; Eriksdottir, Gudny; Smith, Albert V; Gudnason, Vilmunder; Harris, Tamara B; Brouwer, Ingeborg A; Berr, Claudine; Helmer, Catherine; Samieri, Cecilia; Laakso, Markku; Tsai, Michael Y; Giles, Graham G; Nurmi, Tarja; Wagenknecht, Lynne; Schulze, Matthias B; Lemaitre, Rozenn N; Chien, Kuo-liong; Soedamah-Muthu, S.S.; Geleijnse, Johanna M; Sun, Qi; Harris, William S; Lind, Lars; Ärnlöv, Johan; Riserus, Ulf; Micha, Renata; Mozaffarian, Dariush.

In: Lancet Diabetes Endocrinol, Vol. 5, No. 12, 2017, p. 965-974.

Research output: Contribution to journalArticleScientificpeer-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 - Frazier-wood, Alexis C

AU - Bassett, Julie K

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, S.S.

AU - Geleijnse, Johanna M

AU - Sun, Qi

AU - Harris, William S

AU - Lind, Lars

AU - Ärnlöv, Johan

AU - Riserus, Ulf

AU - Micha, Renata

AU - Mozaffarian, Dariush

PY - 2017

Y1 - 2017

N2 - BackgroundThe 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.MethodsWe 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.FindingsParticipants 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).InterpretationFindings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.

AB - BackgroundThe 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.MethodsWe 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.FindingsParticipants 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).InterpretationFindings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.

U2 - 10.1016/S2213-8587(17)30307-8

DO - 10.1016/S2213-8587(17)30307-8

M3 - Article

VL - 5

SP - 965

EP - 974

JO - Lancet Diabetes Endocrinol

JF - Lancet Diabetes Endocrinol

SN - 2213-8587

IS - 12

ER -