Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies

Fumiaki Imamura, Amanda M. Fretts, Matti Marklund, Andres V. Ardisson Korat, Wei Sin Yang, Maria Lankinen, Waqas Qureshi, Catherine Helmer, Tzu An Chen, Jyrki K. Virtanen, Kerry Wong, Julie K. Bassett, Rachel Murphy, Nathan Tintle, Chaoyu Ian Yu, Ingeborg A. Brouwer, Kuo Liong Chien, Yun Yu Chen, Alexis C. Wood, Liana C. Del GobboLuc Djousse, Johanna M. Geleijnse, Graham G. Giles, Janette de Goede, Vilmundur Gudnason, William S. Harris, Allison Hodge, Frank Hu, Albert Koulman, Markku Laakso, Lars Lind, Hung Ju Lin, Barbara McKnight, Kalina Rajaobelina, Ulf Riserus, Jennifer G. Robinson, Cecilia Samieri, Mackenzie Senn, David S. Siscovick, Sabita S. Soedamah-Muthu, Nona Sotoodehnia, Qi Sun, Michael Y. Tsai, Tomi Pekka Tuomainen, Matti Uusitupa, Lynne E. Wagenknecht, Nick J. Wareham, Jason H.Y. Wu, Renata Micha, Rozenn N. Lemaitre

Research output: Contribution to journalArticleAcademicpeer-review

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 States, 1 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 = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. 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 4 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 (I2 = 51.1%-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% confidence interval (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.

Original languageEnglish
Pages (from-to)e1003102
JournalPLOS Medicine
Volume17
Issue number6
DOIs
Publication statusPublished - 12 Jun 2020

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    Imamura, F., Fretts, A. M., Marklund, M., Ardisson Korat, A. V., Yang, W. S., Lankinen, M., ... Lemaitre, R. N. (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