Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.
<h4>Background</h4>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 diabe...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-06-01
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| Series: | PLoS Medicine |
| Online Access: | https://doi.org/10.1371/journal.pmed.1003102 |
| _version_ | 1830359807950848000 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fumiaki Imamura |
| collection | DOAJ |
| description | <h4>Background</h4>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).<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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. |
| first_indexed | 2024-12-20T03:06:02Z |
| format | Article |
| id | doaj.art-8b4202118eac4cb5818ea8b4e67c2043 |
| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-12-20T03:06:02Z |
| publishDate | 2020-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj.art-8b4202118eac4cb5818ea8b4e67c20432022-12-21T19:55:36ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762020-06-01176e100310210.1371/journal.pmed.1003102Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.Fumiaki ImamuraAmanda M FrettsMatti MarklundAndres V Ardisson KoratWei-Sin YangMaria LankinenWaqas QureshiCatherine HelmerTzu-An ChenJyrki K VirtanenKerry WongJulie K BassettRachel MurphyNathan TintleChaoyu Ian YuIngeborg A BrouwerKuo-Liong ChienYun-Yu ChenAlexis C WoodLiana C Del GobboLuc DjousseJohanna M GeleijnseGraham G GilesJanette de GoedeVilmundur GudnasonWilliam S HarrisAllison HodgeFrank HuInterAct ConsortiumAlbert KoulmanMarkku LaaksoLars LindHung-Ju LinBarbara McKnightKalina RajaobelinaUlf RiserusJennifer G RobinsonCecilia SamieriMackenzie SennDavid S SiscovickSabita S Soedamah-MuthuNona SotoodehniaQi SunMichael Y TsaiTomi-Pekka TuomainenMatti UusitupaLynne E WagenknechtNick J WarehamJason H Y WuRenata MichaRozenn N LemaitreDariush MozaffarianNita G Forouhi<h4>Background</h4>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).<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pmed.1003102 |
| spellingShingle | 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 Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. PLoS Medicine |
| title | Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. |
| title_full | Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. |
| title_fullStr | Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. |
| title_full_unstemmed | Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. |
| title_short | Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. |
| title_sort | fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes a pooled analysis of prospective cohort studies |
| url | https://doi.org/10.1371/journal.pmed.1003102 |
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