@article{23347,
  author = {Geleijnse Johanna and Ärnlöv Johan and H Y Wu Jason and Sun Qi and Frazier-Wood Alexis and Siscovick David and Tsai Michael and Hu Frank and Lemaitre Rozenn and Mozaffarian Dariush and Steffen Lyn and Wagenknecht Lynne and Virtanen Jyrki and Marklund Matti and Imamura Fumiaki and Tintle Nathan and Korat Andres and de Goede Janette and Zhou Xia and Yang Wei-Sin and Otto Marcia and Kröger Janine and Qureshi Waqas and Bassett Julie and Lankinen Maria and Murphy Rachel and Rajaobelina Kalina and Del Gobbo Liana and Forouhi Nita and Luben Robert and Khaw Kay-Tee and Wareham Nick and Kalsbeek Anya and Veenstra Jenna and Luo Juhua and Lin Hung-Ju and Boeing Heiner and Chen Tzu-An and Steffen Brian and Hodge Allison and Eriksdottir Gudny and Smith Albert and Gudnason Vilmunder and Harris Tamara and Brouwer Ingeborg and Berr Claudine and Helmer Catherine and Samieri Cecilia and Laakso Markku and Giles Graham and Nurmi Tarja and Schulze Matthias and Chien Kuo-Liong and Soedamah-Muthu Sabita and Harris William and Lind Lars and Riserus Ulf and Micha Renata and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)},
  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 = {<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>FINDINGS: </b>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/m, 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=53·9%, p=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=63·0%, p<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≥0·13).</p><p><b>INTERPRETATION: </b>Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.</p><p><b>FUNDING: </b>Funders are shown in the appendix.</p>},
  year = {2017},
  journal = {Lancet Diabetes Endocrinol},
  volume = {5},
  pages = {965-974},
  issn = {2213-8595},
  doi = {10.1016/S2213-8587(17)30307-8},
  language = {eng},
}