PLoS Medicine (Jun 2020)

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 Gobbo,
  • Luc Djousse,
  • Johanna M Geleijnse,
  • Graham G Giles,
  • Janette de Goede,
  • Vilmundur Gudnason,
  • William S Harris,
  • Allison Hodge,
  • Frank Hu,
  • InterAct Consortium,
  • 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,
  • Dariush Mozaffarian,
  • Nita G Forouhi

DOI
https://doi.org/10.1371/journal.pmed.1003102
Journal volume & issue
Vol. 17, no. 6
p. e1003102

Abstract

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BackgroundDe 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 findingsSeventeen 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 ConclusionsConcentrations 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.