Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

PLoS Med. 2018 Oct 10;15(10):e1002670. doi: 10.1371/journal.pmed.1002670. eCollection 2018 Oct. Imamura F1, Fretts A2, Marklund M3, Ardisson Korat AV4, Yang WS5, Lankinen M6, Qureshi W7, Helmer C8, Chen TA9, Wong K10, Bassett JK10, Murphy R11, Tintle N12, Yu CI13, Brouwer IA14, Chien KL5, Frazier-Wood AC9, Del Gobbo LC15, Djoussé L16, Geleijnse JM17, Giles GG10,18, de Goede J17, Gudnason V19, Harris WS20,21, Hodge A10,18, Hu F4; InterAct Consortium, Koulman A1,22,23,24,25, Laakso M26, Lind L27, Lin HJ28, McKnight B13, Rajaobelina K8, Risérus U3, Robinson JG29, Samieri C8, Siscovick DS30, Soedamah-Muthu SS17,31, Sotoodehnia N2, Sun Q4, Tsai MY32, Uusitupa M6, Wagenknecht LE33, Wareham NJ1, Wu JH34, Micha R35, Forouhi NG1, Lemaitre RN2, Mozaffarian D35; Fatty Acids and Outcomes Research Consortium (FORCE). Author information 1 MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. 2 Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America. 3 Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Sweden. 4 Department of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America. 5 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan. 6 Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. 7 Section of Cardiovascular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Bowman Gray Center, Winston-Salem, North Carolina, United States of America. 8 INSERM, UMR 1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France. 9 USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America. 10 Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Australia. 11 Centre of Excellence in Cancer Prevention, School of Population & Public Health, Faculty of Medicine, The University of British Columbia, Vancouver, Canada. 12 Department of Mathematics and Statistics, Dordt College, Sioux Center, Iowa, United States of America. 13 Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington, United States of America. 14 Department of Health Sciences, Faculty of Earth & Life Sciences, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands. 15 Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. 16 Divisions of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. 17 Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands. 18 Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Australia. 19 Icelandic Heart Association Research Institute, Holtasmári 1, Kópavogur, Iceland, Iceland. 20 Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, United States of America. 21 OmegaQuant Analytics LLC, Sioux Falls, South Dakota, United States of America. 22 National Institute for Health Research Biomedical Research Centres Core Nutritional Biomarker Laboratory, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom. 23 National Institute for Health Research Biomedical Research Centres Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom. 24 Medical Research Council Elsie Widdowson Laboratory, Cambridge, United Kingdom. 25 Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland. 26 Department of Medicine, Kuopio University Hospital, Kuopio, Finland. 27 Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 28 Department of Internal Medicine, National Taiwan University Hospital, Zhongzheng District, Taipei City, Taiwan. 29 Departments of Epidemiology and Medicine at the University of Iowa College of Public Health, Iowa City, Iowa, United States of America. 30 The New York Academy of Medicine, New York, New York, United States of America. 31 Center of Research on Psychology in Somatic Diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands. 32 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America. 33 Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America. 34 The George Institute for Global Health and the Faculty of Medicine, University of New South Wales, Sydney, Australia. 35 Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States of America. Abstract BACKGROUND: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). METHODS AND FINDINGS: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. CONCLUSIONS: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D. PMID: 30303968 DOI: 10.1371/journal.pmed.1002670 Free full text