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

Fumiaki Imamura(University of Cambridge), Amanda M. Fretts(University of Washington), Matti Marklund(Tufts University), Andres V Ardisson Korat(Brigham and Women's Hospital), Wei-Sin Yang(National Taiwan University), Maria Lankinen(University of Eastern Finland), Waqas Qureshi(Wake Forest University), Catherine Helmer(Université de Bordeaux), Tzu-An Chen(Children's Nutrition Research Center at Baylor College of Medicine), Jyrki K. Virtanen(University of Eastern Finland), Kerry LM Wong(Cancer Council Victoria), Julie K. Bassett(Cancer Council Victoria), Rachel A. Murphy(University of British Columbia), Nathan Tintle(Dordt University), Chaoyu Ian Yu(University of Washington), Ingeborg A. Brouwer(Vrije Universiteit Amsterdam), Kuo‐Liong Chien(National Taiwan University), Yun‐Yu Chen(National Taiwan University), Alexis C. Wood(Children's Nutrition Research Center at Baylor College of Medicine), Liana C. Del Gobbo(Stanford University), Luc Djoussé(Brigham and Women's Hospital), Johanna M. Geleijnse(Wageningen University & Research), Graham G. Giles(The University of Melbourne), Janette de Goede(Wageningen University & Research), Vilmundur Guðnason(Icelandic Heart Association), William S. Harris(University of South Dakota), Allison Hodge(The University of Melbourne), Frank B. Hu(Brigham and Women's Hospital), Albert Koulman(MRC Human Nutrition Research), Markku Laakso(University of Eastern Finland), Lars Lind(Uppsala University), Hung-Ju Lin(National Taiwan University Hospital), Barbara McKnight(University of Washington), Kalina Rajaobelina(Université de Bordeaux), Ulf Risérus(Uppsala University), Jennifer G. Robinson(University of Iowa), Cécilia Samieri(Université de Bordeaux), Mackenzie K. Senn(Children's Nutrition Research Center at Baylor College of Medicine), David S. Siscovick(New York Academy of Medicine), Sabita S. Soedamah‐Muthu(Tilburg University), Nona Sotoodehnia(University of Washington), Qi Sun(Brigham and Women's Hospital), Michael Y. Tsai(University of Minnesota), Tomi‐Pekka Tuomainen(University of Eastern Finland), Matti Uusitupa(University of Eastern Finland), Lynne E. Wagenknecht(Wake Forest University), Nicholas J. Wareham(University of Cambridge), Jason Wu(UNSW Sydney), Renata Micha(Tufts University), Rozenn N. Lemaître(University of Washington), Dariush Mozaffarian(Tufts University), Nita G. Forouhi(University of Cambridge)
PLoS Medicine
June 12, 2020
10.1371/journal.pmed.1003102
Cited by 71Open Access
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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.

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