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

Autoři: Fumiaki Imamura aff001;  Amanda M. Fretts aff002;  Matti Marklund aff003;  Andres V. Ardisson Korat aff006;  Wei-Sin Yang aff008;  Maria Lankinen aff009;  Waqas Qureshi aff010;  Catherine Helmer aff011;  Tzu-An Chen aff012;  Jyrki K. Virtanen aff009;  Kerry Wong aff013;  Julie K. Bassett aff013;  Rachel Murphy aff014;  Nathan Tintle aff015;  Chaoyu Ian Yu aff016;  Ingeborg A. Brouwer aff017;  Kuo-Liong Chien aff008;  Yun-yu Chen aff008;  Alexis C. Wood aff012;  Liana C. del Gobbo aff019;  Luc Djousse aff020;  Johanna M. Geleijnse aff021;  Graham G. Giles aff013;  Janette de Goede aff021;  Vilmundur Gudnason aff024;  William S. Harris aff025;  Allison Hodge aff013;  Frank Hu aff006aff001;  Albert Koulman aff001;  Markku Laakso aff030;  Lars Lind aff032;  Hung-Ju Lin aff033;  Barbara McKnight aff016;  Kalina Rajaobelina aff011;  Ulf Riserus aff003;  Jennifer G. Robinson aff034;  Cecilia Samieri aff011;  Mackenzie Senn aff012;  David S. Siscovick aff035;  Sabita S. Soedamah-Muthu aff021;  Nona Sotoodehnia aff038;  Qi Sun aff006;  Michael Y. Tsai aff039;  Tomi-Pekka Tuomainen aff009;  Matti Uusitupa aff009;  Lynne E. Wagenknecht aff040;  Nick J. Wareham aff001;  Jason H. Y. Wu aff004;  Renata Micha aff005;  Rozenn N. Lemaitre aff038;  Dariush Mozaffarian aff005;  Nita G. Forouhi aff001
Působiště autorů: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom aff001;  Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America aff002;  Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden aff003;  The George Institute for Global Health, the Faculty of Medicine, University of New South Wales, Sydney, Australia aff004;  Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America aff005;  Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America aff006;  Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America aff007;  Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, the Republic of China aff008;  Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland aff009;  Section of Cardiovascular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America aff010;  INSERM, UMR 1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France aff011;  USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America aff012;  Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia aff013;  Centre of Excellence in Cancer Prevention, School of Population & Public Health, Faculty of Medicine, The University of British Columbia, Vancouver, Canada aff014;  Department of Mathematics and Statistics, Dordt University, Sioux Center, Iowa, United States of America aff015;  Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington, United States of America aff016;  Department of Health Sciences, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands aff017;  Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, the Republic of China aff018;  Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America aff019;  Divisions of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America aff020;  Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands aff021;  Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Australia aff022;  Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia aff023;  Icelandic Heart Association Research Institute, Kopavogur, Iceland aff024;  Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, United States of America aff025;  OmegaQuant Analytics, Sioux Falls, South Dakota, United States of America aff026;  National Institute for Health Research Biomedical Research Centres Core Nutritional Biomarker Laboratory, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom aff027;  National Institute for Health Research Biomedical Research Centres Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom aff028;  Medical Research Council Elsie Widdowson Laboratory, Cambridge, United Kingdom aff029;  Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland aff030;  Department of Medicine, Kuopio University Hospital, Kuopio, Finland aff031;  Department of Medical Sciences, Uppsala University, Uppsala, Sweden aff032;  Department of Internal Medicine, National Taiwan University Hospital, Taipei City, the Republic of China aff033;  Preventive Intervention Center, Departments of Epidemiology, the University of Iowa College of Public Health, Iowa City, Iowa, United States of America aff034;  The New York Academy of Medicine, New York, New York, United States of America aff035;  Center of Research on Psychological and Somatic disorders, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands aff036;  Institute for Food, Nutrition and Health, University of Reading, Reading, United Kingdom aff037;  Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America aff038;  Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America aff039;  Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America aff040
Vyšlo v časopise: Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. PLoS Med 17(6): e1003102. doi:10.1371/journal.pmed.1003102
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003102



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.


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.

Klíčová slova:

Fatty acids – Lipid analysis – Lipids – Lipogenesis – Metaanalysis – Phospholipids – Type 2 diabetes – United States


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