期刊
PLOS MEDICINE
卷 17, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pmed.1003102
关键词
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资金
- United Kingdom Medical Research Council Epidemiology Unit core grant [MC_UU_12015/5, MC_UU_12015/1]
- National Institute for Health Research (NIHR) Biomedical Research Centre Cambridge [IS-BRC-1215-20014]
- Dutch Scientific Organization (ZonMW)
- Foundation Plan Alzheimer
- NIH [3T32DK007703, T32CA009001, UM1 CA167552, R01 HL35464, AA11181, HL35464, CA55075, HL60712, P30 DK46200, M01-RR-43, CA186107, CA87969, CA49449, HL34594, CA167552, HL088521]
- Netherlands Heart Foundation [2000T401]
- NIH (NIH/National Heart, Lung, and Blood Institute [NHLBI])
- NIH (ODS) [R01HL-076200]
- Unilever RD, Vlaardingen
- United States National Institute of Health (NIH) [N01-AG012100]
- National Institute of Aging (NIA) Intramural Research Program
- Hjartavernd (the Icelandic Heart Association)
- Althingi (the Icelandic Parliament)
- Michael Smith Foundation for Medical Research [17644]
- Canadian Cancer Society [704735]
- Ministry of Science and Technology
- National Taiwan University, Taiwan [MOST 103-2314-B-002 -135-MY3, NSC 100-2314-B-002 -113 -MY3, NTUH 105-S3120, NTUH 106-S3453]
- National Institute of Neurological Disorders and Stroke (NINDS)
- NIA [R01AG023629]
- NHLBI
- Boston University [N01-HC25195]
- EU FP6 programme [LSHM_CT_2006_037197]
- Academy of Finland
- VicHealth
- Cancer Council Victoria
- Australia's National Health and Medical Research Council [209057, 126403]
- NCRR [UL1-TR000040, UL1-TR-001079]
- European Union
- Juselius Foundation
- Uppsala University Hospital
- Swedish Research Council for Health, Working Life and Welfare
- Agence Nationale de la Recherche [COGINUT ANR-06-PNRA-005]
- Fondation Plan Alzheimer [FCS 2009-2012]
- Uppsala City Council
- Swedish Research Council
- Swedish Diabetes Foundation (UR)
- NHLBI, NIH, U.S. Department of Health and Human Services [HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C]
- Fondation pour la Recherche Medicale
- 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
- Caisse Nationale pour la Solidarite et l'Autonomie
- NHLBI [HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01-HL-085710, U01HL080295, U01HL130114, U01-HL-47892, U01-HL-47902, N01-HC-95161, N01-HC-95162, N01-HC95163, N01-HC-95164, N01-HC-95165, N01-HC95166, N01-HC-95167, N01-HC-95168, N01HC-95169]
- [DK-29867]
- [R01-58329]
- [DK-079888]
- [HHSN268201500003I]
- [N01-HC-95159]
- [N01-HC95160]
- MRC [MC_UU_12015/5, MC_UU_00006/3, MC_UU_12015/1, MC_UU_00014/5] Funding Source: UKRI
Background 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-varianceweighted 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 (I-2 = 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. Conclusions 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.
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