05097nas a2200817   4500000000100000008004100001100002200042700001900064700001700083700001100100700002400111700002000135700001700155700001300172700002000185700002400205700001600229700002200245700001900267700001900286700002000305700001800325700001700343700002100360700001300381700001700394700001600411700001900427700001800446700001800464700001900482700001800501700002300519700002000542700001700562700001700579700001700596700001700613700001800630700001900648700001400667700001600681700001800697700001600715700001800731700001800749700002200767700001700789700002300806700001800829700002100847700001800868700002100886700002000907700001800927700001700945700001600962700002100978700002000999700002601019700001901045700001401064700001601078700001701094700012701111245016101238300001201399490000601411520284801417022001404265       2017                            d1 aGeleijnse Johanna1 aÄrnlöv Johan1 aH Y Wu Jason1 aSun Qi1 aFrazier-Wood Alexis1 aSiscovick David1 aTsai Michael1 aHu Frank1 aLemaitre Rozenn1 aMozaffarian Dariush1 aSteffen Lyn1 aWagenknecht Lynne1 aVirtanen Jyrki1 aMarklund Matti1 aImamura Fumiaki1 aTintle Nathan1 aKorat Andres1 ade Goede Janette1 aZhou Xia1 aYang Wei-Sin1 aOtto Marcia1 aKröger Janine1 aQureshi Waqas1 aBassett Julie1 aLankinen Maria1 aMurphy Rachel1 aRajaobelina Kalina1 aDel Gobbo Liana1 aForouhi Nita1 aLuben Robert1 aKhaw Kay-Tee1 aWareham Nick1 aKalsbeek Anya1 aVeenstra Jenna1 aLuo Juhua1 aLin Hung-Ju1 aBoeing Heiner1 aChen Tzu-An1 aSteffen Brian1 aHodge Allison1 aEriksdottir Gudny1 aSmith Albert1 aGudnason Vilmunder1 aHarris Tamara1 aBrouwer Ingeborg1 aBerr Claudine1 aHelmer Catherine1 aSamieri Cecilia1 aLaakso Markku1 aGiles Graham1 aNurmi Tarja1 aSchulze Matthias1 aChien Kuo-Liong1 aSoedamah-Muthu Sabita1 aHarris William1 aLind Lars1 aRiserus Ulf1 aMicha Renata1 aCohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)00aOmega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies.  a965-9740 v53 a<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>  a2213-8595