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.
Bibliographical noteFunding Information:
FI, NGF, and NJW were funded by the United Kingdom Medical Research Council Epidemiology Unit core grant (MC_UU_12015/1 and MC_UU_12015/5); NGF, NJW, and AK acknowledge National Institute for Health Research Biomedical Research Centre Cambridge (IS-BRC-1215-20014); IAB, by the European Union (FP7 and Horizon2020) and the Dutch Scientific Organisation (ZonMW); CS, by the Fondation Plan Alzheimer; and AVAK, by the National Institute of Health (NIH) training grant (3T32DK007703). The AOC was funded by the Netherlands Heart Foundation (grant 2000T401), the NIH (NIH/ National Heart, Lung, and Blood Institute [NHLBI], and ODS, grant R01HL- 076200), and Unilever R&D, Vlaardingen (margarine production and distribution); Age, Gene/Environment Susceptibility Study Reykjavik, by Office of Dietary Supplements, NIH (N01-AG012100), the National Institute of Aging (NIA) Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament); Chin-Shan Community Cardiovascular Study, by Ministry of Science and Technology and National Taiwan University (MOST 103-2314-B-002 -135 –MY3, NSC 100-2314-B-002 -113 –MY3, NTUH 105-S3120, NTUH 106-S3453); Cardiovascular Health Study, by NHLBI (HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grants U01HL080295 and U01HL130114), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS) and NIA (R01AG023629; Framingham Heart Study, NHLBI in collaboration with Boston University (N01-HC-25195); Health Professionals Follow-up Study, by NIH (UM1 CA167552, R01 HL35464, AA11181, HL35464, CA55075, HL60712, and P30 DK46200); Insulin Resistance Atherosclerosis Study, by NIH (M01-RR-43) and NHLBI (U01-HL-47892, U01-HL-47902, DK-29867, R01-58329, and DK-079888; InterAct, by the EU FP6 programme (LSHM_CT_2006_037197); Melbourne Collaborative Cohort Study, by VicHealth and Cancer Council Victoria and by Australia’s National Health and Medical Research Council (209057, 251553, and 126403); Multi-ethnic Study of Atherosclerosis, by NHLBI (HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169) and NCRR (UL1-TR-000040 and UL1-TR-001079); Metabolic Syndrome in Men Study, by the European Union, the Academy of Finland, and the Juselius Foundation; Nurses’ Health Study, by NIH (CA186107, CA87969, CA49449, HL34594, HL35464, CA167552, HL60712, and HL088521); Prospective Investigation of the Vascularture in Uppsala Seniors, by Uppsala University Hospital and the Swedish Research Council for Health, Working Life and Welfare; Tree City Study, by the Fondation pour la Recherche Medicale, the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Conseils Regionaux d’Aquitaine et Bourgogne, Fondation de France, Ministry of Research–Institut National de la Sante and de la Recherche Medicale Programme Cohortes, Agence Nationale de la Recherche (COGINUT ANR-06-PNRA-005), Fondation Plan Alzheimer (FCS 2009-2012), and the Caisse Nationale pour la Solidarite et l’Autonomie, under a partnership agreement between the Institut National de la Sante et de la Recherche Medicale, the University Bordeaux 2 Victor Segalen; Uppsala Longitudinal Studies of Adult Men 50 and 70, by the Swedish Research Council for Health, Working Life and Welfare, Uppsala City Council, and Swedish Research Council; Women’s Health Initiative, by the NHLBI, NIH, U.S. Department of Health and Human Services (HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors acknowledge Eveline Waterham, Wageningen University, Wageningen, the Netherlands, for analyses of data from the Alpha Omega Cohort (AOC). Information on InterAct Consortium and FORCE can be found at http://www.inter-act.eu/ and http://force.nutrition.tufts.edu/about. Disclaimer This manuscript does not reflect the opinions or conclusions of any funding agency. The funders and funding organizations for participating cohorts had no role in study design, data collection, data analysis, interpretation of the data, preparation of the manuscript, and the decision to submit.