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, Johanna M. Geleijnse, Qi Sun, William Harris, Lars Lind, Johan Ärnlöv, Ulf Riserus, Renata Micha, Dariush Mozaffarian

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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; I 2=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; I 2=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

Original languageEnglish (US)
JournalThe Lancet Diabetes and Endocrinology
DOIs
StateAccepted/In press - 2017
Externally publishedYes

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

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., ... Mozaffarian, D. (Accepted/In press). 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. https://doi.org/10.1016/S2213-8587(17)30307-8