Amanda M Fretts1,2, Fumiaki Imamura3, Matti Marklund4, Renata Micha5, Jason H Y Wu6, Rachel A Murphy7, Kuo-Liong Chien8,9, Barbara McKnight2,10, Nathan Tintle11, Nita G Forouhi3, Waqas T Qureshi12, Jyrki K Virtanen13, Kerry Wong14, Alexis C Wood15, Maria Lankinen13, Kalina Rajaobelina16, Tamara B Harris17, Luc Djoussé18, Bill Harris19,20, Nick J Wareham3, Lyn M Steffen21, Markku Laakso22, Jenna Veenstra23, Cécilia Samieri16, Ingeborg A Brouwer24, Chaoyu Ian Yu10, Albert Koulman3,25,26,27, Brian T Steffen28, Catherine Helmer16, Nona Sotoodehnia2,29, David Siscovick30, Vilmundur Gudnason31,32, Lynne Wagenknecht33, Sari Voutilainen13, Michael Y Tsai28, Matti Uusitupa13, Anya Kalsbeek23, Claudine Berr34,35, Dariush Mozaffarian5, Rozenn N Lemaitre2,29. 1. Department of Epidemiology. 2. Cardiovascular Health Research Unit. 3. MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. 4. Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. 5. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA. 6. The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia. 7. School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. 8. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. 9. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 10. Department of Biostatistics. 11. Department of Statistics. 12. Division of Cardiovascular Medicine. 13. Institute of Public Health and Clinical Nutrition. 14. Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia. 15. USDA / Agricultural Research Service Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX. 16. University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Bordeaux, France. 17. National Institute on Aging, NIH, Bethesda, MD. 18. Divisions of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 19. OmegaQuant Analytics, Sioux Falls, SD. 20. Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Vermillion, SD. 21. Division of Epidemiology and Community Health, School of Public Health. 22. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland. 23. Department of Biology, Dordt College, Sioux Center, IA. 24. Department of Health Sciences, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. 25. National Institute for Health Research Biomedical Research Centres Core Nutritional Biomarker Laboratory. 26. National Institute for Health Research Biomedical Research Centres Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom. 27. Medical Research Council Elsie Widdowson Laboratory, Cambridge, United Kingdom. 28. Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN. 29. Department of Medicine, University of Washington, Seattle, WA. 30. New York Academy of Medicine, New York, NY. 31. Icelandic Heart Association, Kópavogur, Iceland. 32. Faculty of Medicine, University of Iceland, Reyjavik, Iceland. 33. Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC. 34. Inserm, University of Montpellier, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France. 35. Memory Research and Resources Center, Department of Neurology, Montpellier University Hospital, Montpellier, France.
Abstract
BACKGROUND: Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed. OBJECTIVE: We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies. METHODS: Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants. RESULTS: There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides. CONCLUSIONS: Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.
BACKGROUND:Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed. OBJECTIVE: We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies. METHODS: Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants. RESULTS: There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides. CONCLUSIONS: Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.
Keywords:
Cohorts for Heart and Aging Research in Genomic Epidemiology; Fatty Acids and Outcomes Research Consortium; diabetes; meta-analysis; saturated fatty acids; very-long-chain saturated fatty acids
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