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

Heidi T M 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 H Y 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
Fatty Acids and Outcomes Research Consortium (FORCE)

Publication Date

4-1-2022

Journal

Diabetes Care

DOI

10.2337/dc21-1756

PMID

35142845

PMCID

PMC9114723

PubMedCentral® Posted Date

2-10-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Adolescent, Adult, Biomarkers, Cohort Studies, Diabetes Mellitus, Type 2, Fatty Acids, Humans, Outcome Assessment, Health Care, Prospective Studies, Risk Factors, Trans Fatty Acids

Abstract

Objective: 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.

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 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.

Results: 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).

Conclusions: 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.