Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.
Authors
Fretts, Amanda M
Yang, Wei-Sin
Helmer, Catherine
Chen, Tzu-An
Virtanen, Jyrki K
Murphy, Rachel
Yu, Chaoyu Ian
Del Gobbo, Liana C
Djousse, Luc
Hu, Frank
InterAct Consortium,
Laakso, Markku
Lind, Lars
Lin, Hung-Ju
Rajaobelina, Kalina
Robinson, Jennifer G
Sotoodehnia, Nona
Tsai, Michael Y
Uusitupa, Matti
Wagenknecht, Lynne E
Lemaitre, Rozenn N
Publication Date
2020-06-12Journal Title
PLoS medicine
ISSN
1549-1277
Publisher
Public Library of Science (PLoS)
Volume
17
Issue
6
Pages
e1003102
Language
eng
Type
Article
This Version
AM
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
Imamura, F., Fretts, A. M., Marklund, M., Ardisson Korat, A. V., Yang, W., Lankinen, M., Qureshi, W., et al. (2020). Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.. PLoS medicine, 17 (6), e1003102. https://doi.org/10.1371/journal.pmed.1003102
Abstract
Abstract
Background: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D).
Methods and Findings: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States1 from Australia, 1 from Taiwan; baseline years=1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages=52.3 to 75.5 years; % women=20.4% to 62.3% in twelve cohorts recruiting both sexes).) and 15,383 incident cases of T2D over the 9-year follow-up on averages. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the four fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p<0.001) for 16:0, 1.40 (1.33-1.48; p<0.001) for 16:1n-7, 1.14 (1.05-1.22; p=0.001) for 18:0, and 1.16 (1.07-1.25; p<0.001) for 18:1n9. Heterogeneity was seen across cohorts (I squared=51.1% to 73.1% for each fatty acid), but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0, but were attenuated for 18:1n9 (RR=1.03, 95% CI=0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors.
Conclusions: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.
Keywords
InterAct Consortium, Humans, Diabetes Mellitus, Type 2, Fatty Acids, Incidence, Prospective Studies, Aged, Middle Aged, Female, Male, Lipogenesis, Metabolic Networks and Pathways
Sponsorship
FI, NGF, and NJW were funded by the United Kingdom Medical Research Council Epidemiology Unit core grant (MC_UU_12015/5 and MC_UU_12015/1); NJW, NGF and AK acknowledge National Institute for Health Research (NIHR) Biomedical Research Centre Cambridge (IS-BRC-1215-20014); NJW is an NIHR Senior Investigator;
Funder references
MRC (MC_UU_12015/5)
MRC (MC_UU_12015/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Embargo Lift Date
2023-05-01
Identifiers
External DOI: https://doi.org/10.1371/journal.pmed.1003102
This record's URL: https://www.repository.cam.ac.uk/handle/1810/304930
Rights
All rights reserved