TY - JOUR
T1 - Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes
T2 - A pooled analysis of prospective cohort studies
AU - Imamura, Fumiaki
AU - Fretts, Amanda M.
AU - Marklund, Matti
AU - Ardisson Korat, Andres V.
AU - Yang, Wei Sin
AU - Lankinen, Maria
AU - Qureshi, Waqas
AU - Helmer, Catherine
AU - Chen, Tzu An
AU - Virtanen, Jyrki K.
AU - Wong, Kerry
AU - Bassett, Julie K.
AU - Murphy, Rachel
AU - Tintle, Nathan
AU - Yu, Chaoyu Ian
AU - Brouwer, Ingeborg A.
AU - Chien, Kuo Liong
AU - Chen, Yun Yu
AU - Wood, Alexis C.
AU - Del Gobbo, Liana C.
AU - Djousse, Luc
AU - Geleijnse, Johanna M.
AU - Giles, Graham G.
AU - de Goede, Janette
AU - Gudnason, Vilmundur
AU - Harris, William S.
AU - Hodge, Allison
AU - Hu, Frank
AU - Koulman, Albert
AU - Laakso, Markku
AU - Lind, Lars
AU - Lin, Hung Ju
AU - McKnight, Barbara
AU - Rajaobelina, Kalina
AU - Riserus, Ulf
AU - Robinson, Jennifer G.
AU - Samieri, Cecilia
AU - Senn, Mackenzie
AU - Siscovick, David S.
AU - Soedamah-Muthu, Sabita S.
AU - Sotoodehnia, Nona
AU - Sun, Qi
AU - Tsai, Michael Y.
AU - Tuomainen, Tomi Pekka
AU - Uusitupa, Matti
AU - Wagenknecht, Lynne E.
AU - Wareham, Nick J.
AU - Wu, Jason H.Y.
AU - Micha, Renata
AU - Lemaitre, Rozenn N.
PY - 2020/6/12
Y1 - 2020/6/12
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pmed.1003102
DO - 10.1371/journal.pmed.1003102
M3 - Article
C2 - 32530938
AN - SCOPUS:85086523590
SN - 1549-1676
VL - 17
JO - PLOS Medicine
JF - PLOS Medicine
IS - 6
M1 - e1003102
ER -
