Trans fatty acid biomarkers and incident type 2 diabetes: Pooled analysis of 12 prospective cohort studies in the Fatty Acids and Outcomes Research Consortium (FORCE)

Authors: LAI, HEIDI - Friedman School At Tufts; IMAMURA, FUMIAKI - University Of Cambridge; ARDISSON KORAT, ANDRES - Harvard School Of Public Health; MURPHY, RACHEL - University Of British Columbia; TINTLE, NATHAN - Fatty Acid Research Institute; BASSETT, JULIE - Cancer Council Victoria; CHEN, JIAYING - Brigham & Women'S Hospital; KRÖGER, JANINE - German Institute Of Human Nutrition; CHIEN, KUO - National Taiwan University; SENN, MACKENZIE - Children'S Nutrition Research Center (CNRC); WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); FOROUHI, NITA - University Of Cambridge; SCHULZE, MATTHIAS - German Institute Of Human Nutrition; HARRIS, WILLIAM - Fatty Acid Research Institute; VASAN, RAMACHANDRAN - Boston University Medical School; HU, FRANK - Harvard School Of Public Health; GILES, GRAHAM - Cancer Council Victoria; HODGE, ALLISON - Cancer Council Victoria; DJOUSSE, LUC - Brigham & Women'S Hospital; BROUWER, INGEBORG - Vrije University; QIAN, FRANK - Harvard School Of Public Health; SUN, QI - Harvard School Of Public Health; WU, JASON - University Of New South Wales; MARKLUND, MATTI - Friedman School At Tufts; LEMAITRE, ROZENN - University Of Washington; SISCOVICK, DAVID - New York Academy Of Medicine; FRETTS, AMANDA - University Of Washington; SHADYAB, ALADDIN - University Of California, San Diego; MANSON, JOANN - Harvard School Of Public Health; HOWARD, BARBARA - Georgetown University Medical Center; ROBINSON, JENNIFER - University Of Iowa; WALLACE, ROBERT - University Of Iowa; WAREHAM, NICK - University Of Cambridge; CHEN, YII - Harbor-Ucla Medical Center; ROTTER, JEROME - Harbor-Ucla Medical Center; TSAI, MICHAEL - University Of Minnesota; MICHA, RENATA - Friedman School At Tufts; MOZAFFARIAN, DARIUSH - Friedman School At Tufts

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2022
Publication Date: 2/10/2022
Citation: Lai, H.T., Imamura, F., Ardisson Korat, A.V., Murphy, R.A., Tintle, N., Bassett, J.K., Chen, J., Kröger, J., Chien, K.L., Senn, M., Wood, A.C., Forouhi, N.G., Schulze, M.B., Harris, W.S., Vasan, R.S., Hu, F., Giles, G.G., Hodge, A., Djousse, L., Brouwer, I.A., Qian, F., Sun, Q., Wu, J.H., Marklund, M., Lemaitre, R., Siscovick, D.S., Fretts, A.M., Shadyab, A.H., Manson, J.E., Howard, B.V., Robinson, J.G., Wallace, R.B., Wareham, N.J., Chen, Y.D., Rotter, J.I., Tsai, M.Y., Micha, R., Mozaffarian, D. 2022. Trans fatty acid biomarkers and incident type 2 diabetes: Pooled analysis of 12 prospective cohort studies in the Fatty Acids and Outcomes Research Consortium (FORCE). Diabetes Care. 45(4):854-863. https://doi.org/10.2337/dc21-1756.
DOI: https://doi.org/10.2337/dc21-1756

Interpretive Summary: Trans-fatty acids (TFAs) are a type of fat found in the diet that are thought to effect the body by increasing the risk of developing type 2 diabetes (T2D). However, current scientific evidence shows that the amount of TFAs eaten increasing the likelihood of developing T2D remains uncertain. To address this, we examined associations between the onset of T2D and levels of four TFAs in the blood. Our analyses found that circulating levels of two TFAs (trans-18:1 and trans-18:2) were not associated with the onset of T2D, but circulating levels of two other TFAs (trans-16:1n-9 and ttrans-18:2) were associated with the onset of T2D. These novel differences between the TFAs in terms of their association with T2D may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), which is an important avenue for future research aimed at understanding how diet may be used to prevent the onset of T2D.

Technical Abstract: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis. We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged >=18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics. During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94–1.25); cis/trans-18:2, 0.89 (0.73–1.07); and trans/cis-18:2, 0.87 (0.73–1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67–0.99], 0.86 [0.75–0.99], and 0.84 [0.74–0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P>=0.1). Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.