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

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.

BT - Lancet Diabetes Endocrinol C1 - https://www.ncbi.nlm.nih.gov/pubmed/29032079?dopt=Abstract DO - 10.1016/S2213-8587(17)30307-8 IS - 12 J2 - Lancet Diabetes Endocrinol LA - eng N2 -

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.

PY - 2017 SP - 965 EP - 974 T2 - Lancet Diabetes Endocrinol TI - 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. VL - 5 SN - 2213-8595 ER -