Omega-6 fatty acid biomarkers and incident type 2 diabetes: Pooled analysis of individual-level data for 39740 adults from 20 prospective cohort studies

Authors: WU, JASON - University Of Sydney; MARKLUND, MATTI - Uppsala University; IMAMURA, FUMIAKI - University Of Cambridge; TINTLE, NATHAN - Dordt College; KORAT, ANDRES - Harvard School Of Public Health; DE GOEDE, JANETTE - Wageningen University; ZHOU, XIA - University Of Minnesota; YANG, WEI - National Taiwan University; OTTO, MARCIA - University Of Texas Health Science Center; KROGER, JANINE - German Institute Of Human Nutrition; QURESHI, WAQAS - Wake Forest University; VIRTANEN, JYRKI - University Of Eastern Finland; BASSETT, JULIE - Cancer Council Victoria; FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); LANKINEN, MARIA - University Of Eastern Finland; MURPHY, RACHEL - University Of British Columbia; RAJAOBELINA, KALINA - Institut National De La Sante Et De La Recherche Medicale (INSERM)

Submitted to: Lancet Diabetes Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/7/2017
Publication Date: 10/11/2017
Citation: Wu, J.H., Marklund, M., Imamura, F., Tintle, N., Korat, A.V., de Goede, J., Zhou, X., Yang, W.S., Otto, M.C., Kroger, J., Qureshi, W., Virtanen, J.K., Bassett, J., Frazier-Wood, A.C., Lankinen, M., Murphy, R.A., Rajaobelina, K., Del Gobbo, L.C., Forouhi, N.G., Luben, R., Khaw, K.T., Wareham, N., Kalsbeek, A., Veenstra, J., Luo, J., Hu, F.B., Lin, H.J., Siscovick, D.S., Boeing, H., Chen, T.A., Steffen, B., Steffen, L.M., Hodge, A., Eriksdottir, G., Smith, A.V., Gudnason, V., Harris, T.B., Brouwer, I.A., Berr, C., Helmer, C., Samieri, C., Laakso, M., Tsai, M.Y., Giles, G.G., Nurmi, T., Wagenknecht, L., Schulze, M.B., Lemaitre, R.N., Chien, K.L., Soedamah-Muthu, S.S., Geleijnse, J.M., Sun, Q., Harris, W.S., 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 39740 adults from 20 prospective cohort studies. Lancet Diabetes Endocrinology. http://dx.doi.org/10.1016/S2213-8587(17)30307-8.

Interpretive Summary: Unsaturated fatty acids are a form of fat found in foods such as avocados and nuts, which seem to convey protection against cardiovascular disease. Thus dietary guidelines for health, such as those issued by the USDA and the American Heart Association do not limit these types of fats. However, the problem is that fat can be unhealthy, and it is not known if one class of unsaturated fatty acid, known as omega-6 which may have inflammatory effects in the body, increases the risk for conditions other than cardiovascular disease such as type 2 diabetes. Therefore, we included data across on nearly 40,000 adults and examined the association of two omega-6 fatty acids measured in the blood when data collection started, with the development of type 2 diabetes over time. One omega-6 fatty acid (linoleic acid) was associated with 35% lower risk of developing diabetes, while another (arachidonic acid) was not associated with the likelihood of developing diabetes. These findings suggest a long-term benefit of linoleic acid, but not of arachidonic acid on preventing diabetes, although they suggest arachidonic acid is not harmful. This information will be helpful for developing dietary guidelines for the prevention of chronic diseases such as diabetes, and for healthcare practitioners who need to disseminate this information to patients.

Technical Abstract: 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. 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 United Kingdom, 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. 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%, p heterogeneity=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%, p heterogeneity<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 heterogeneity=0.13). Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.