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)

Nita G Forouhi,Jerome I Rotter,Barbara V Howard,Rachel A Murphy,David S Siscovick,Jennifer G Robinson,Robert B Wallace,Michael Y Tsai,Amanda M Fretts,Alexis C Wood,Fumiaki Imamura,Frank Qian,Janine Kröger,Aladdin H Shadyab,Ramachandran S Vasan,Matthias B Schulze,Mackenzie Senn,Allison Hodge,Heidi Lai ,Graham G Giles,Dariush Mozaffarian,Matti Marklund,William S Harris,Julie K Bassett,Qi Sun,Renata Micha,Ingeborg A Brouwer,Jiaying Chen,Joann E Manson,Nathan L Tintle ,Kuo‐Liong Chien ,Jason Wu ,Nick Wareham ,Frank B Hu ,Andres V Ardisson Korat ,Luc Djoussé ,Rozenn N Lemaître ,Yii‐Der Ida Chen ,The Fatty Acids And Outcomes Research Consortium

doi:10.2337/figshare.18396443

Abstract

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: <a>We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers </a>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.

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