Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies
Creators: name: Imamura, Fumiaki
name: Fretts, Amanda M.
name: Marklund, Matti
name: Ardisson Korat, Andres V.
name: Yang, Wei-Sin
name: Lankinen, Maria
name: Qureshi, Waqas
name: Helmer, Catherine
name: Chen, Tzu-An
name: Virtanen, Jyrki K.
name: Wong, Kerry
name: Bassett, Julie K.
name: Murphy, Rachel
name: Tintle, Nathan
name: Yu, Chaoyu Ian
name: Brouwer, Ingeborg A.
name: Chien, Kuo-Liong
name: Chen, Yun-Yu
name: Wood, Alexis C.
name: Del Gobbo, Liana C.
name: Djousse, Luc
name: Geleijnse, Johanna M.
name: Giles, Graham G.
name: De Goede, Janette
name: Gudnason, Vilmundur
name: Harris, William S.
name: Hodge, Allison
name: Hu, Frank
name: InterAct Consortium
name: Koulman, Albert
name: Laakso, Markku
name: Lind, Lars
name: Lin, Hung-Ju
name: McKnight, Barbara
name: Rajaobelina, Kalina
name: Riserus, Ulf
name: Robinson, Jennifer G.
name: Samieri, Cecilia
name: Senn, Mackenzie
name: Siscovick, David S.
name: Soedamah-Muthu, Sabita S.
name: Sotoodehnia, Nona
name: Sun, Qi
name: Tsai, Michael Y.
name: Tuomainen, Tomi-Pekka
name: Uusitupa, Matti
name: Wagenknecht, Lynne E.
name: Wareham, Nick J.
name: Wu, Jason H. Y.
name: Micha, Renata
name: Lemaitre, Rozenn N.
name: Mozaffarian, Dariush
name: Forouhi, Nita G.
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: subject: Research Article
subject: Biology and life sciences
subject: Medicine and health sciences
subject: Research and analysis methods
subject: Physical sciences
subject: FOS: Physical sciences
subject: FOS: Physical sciences
subject: People and places

description: Funder: Dutch Scientific Organization
description: Funder: Foundation Plan Alzheimer
description: Funder: Icelandic Heart Association
description: Funder: Academy of Finland
description: Funder: VicHealth and Cancer Council Victoria
description: Funder: Juselius Foundation
description: Funder: Uppsala University Hospital and the Swedish Research Council for Health, Working Life and Welfare
description: Funder: the Institut National de la Sante et de la Recherche Medicale
description: Funder: , the University Bordeaux 2 Victor Segalen
description: Funder: Sanofi; funder-id: http://dx.doi.org/10.13039/100004339
description: Funder: Fondation pour la Recherche Medicale, the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Conseils Regionaux d’Aquitaine et Bourgogne, Fondation de France, Ministry of Research–Institut National de la Sante and de la Recherche Medicale Programme Cohortes
description: Funder: Caisse Nationale pour la Solidarite et l’Autonomie
description: Funder: Swedish Research Council for Health, Working Life and Welfare, Uppsala City Council, Swedish Research Council, and Swedish Diabetes Foundation
description: 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 &lt; 0.001) for 16:0, 1.40 (1.33–1.48; p &lt; 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 &lt; 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.