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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)

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posted on 10.02.2022, 15:51 by Heidi TM. Lai, Fumiaki Imamura, Andres V. Ardisson Korat, Rachel A. Murphy, Nathan Tintle, Julie K. Bassett, Jiaying Chen, Janine Kröger, Kuo-Liong Chien, Mackenzie Senn, Alexis C. Wood, Nita G. Forouhi, Matthias B. Schulze, William S. Harris, Ramachandran S. Vasan, Frank Hu, Graham G. Giles, Allison Hodge, Luc Djousse, Ingeborg A. Brouwer, Frank Qian, Qi Sun, Jason HY. Wu, Matti Marklund, Rozenn N. Lemaitre, David S. Siscovick, Amanda M. Fretts, Aladdin H. Shadyab, JoAnn E. Manson, Barbara V. Howard, Jennifer G. Robinson, Robert B. Wallace, Nick J. Wareham, Yii-Der Ida Chen, Jerome I. Rotter, Michael Y. Tsai, Renata Micha, Dariush Mozaffarian, the Fatty Acids and Outcomes Research Consortium (FORCE)
Objective: Trans-fatty acids (TFAs) have harmful biologic effects that could increase risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFAs biomarkers and T2D by conducting an individual participant-level pooled analysis.

Research design and methods: 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 1990-2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a pre-specified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.

Results: During 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, RR, 95%CI: 1.09 (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, 95%CI: 0.81, 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 pre-specified sources of potential heterogeneity (each P ≥0.1).

Conclusion: 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.


Individual funding, cohort specific funding, and acknowledgements are included in the appendix. The funders of the study had no role in study design, data collection, data analysis, writing of the report, or the decision to submit for publication.