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Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes
- Source :
- PLOS Medicine, 17(6). Nature Publishing Group, PLoS Medicine, PLOS Medicine 17 (2020) 6, PLoS Medicine, Public Library of Science, 2020, 17 (6), pp.e1003102. ⟨10.1371/journal.pmed.1003102⟩, PLoS Medicine, 17(6):e1003102, 1-17. Nature Publishing Group, PLOS Medicine, 17(6), PLoS Medicine, Vol 17, Iss 6, p e1003102 (2020), InterAct Consortium 2020, ' Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes : A pooled analysis of prospective cohort studies ', PLoS Medicine, vol. 17, no. 6, e1003102, pp. 1-17 . https://doi.org/10.1371/journal.pmed.1003102
- Publication Year :
- 2020
-
Abstract
- 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-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. 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.<br />Fumiaki Imamura and colleagues investigate the association between concentrations of fatty acid involved in de-novo lipogensis and incidence of Type 2 diabetes.<br />Author summary Why was this study done? De novo lipogenesis (DNL) is a metabolic pathway involved in the endogenous synthesis of specific fatty acids, such as 16:0, 16:1n7, 18:0, and 18:1n9, and it is linked to the pathophysiology of cardiometabolic diseases, including type 2 diabetes (T2D). Circulating or tissue concentrations of these fatty acids have been investigated for the associations with T2D incidence in epidemiological research. However, published studies reported inconsistent associations inconsistently and were subject to publication bias. Summary evidence is not available to date for the associations between these fatty acids and T2D incidence. An integration of available cohort studies would increase statistical power and allow assessment of generalizability, standardization of analytical strategies, and evidence synthesis with the potential publication bias minimized. What did the researchers do and find? As a part of the Fatty Acids and Outcomes Research Consortium (FORCE), we conducted new individual-participant data analyses of 17 cohort studies of a total of 65,225 adults free of T2D at baseline, among whom 15,383 developed incident T2D over up to 20 years of follow-up. The cohort studies analyzed the associations between fatty acids (16:0, 16:1n7, 18:0, and 18:1n9) and the risk of developing T2D with standardized analytic strategy. In pooled analyses, each of the fatty acids was positively associated with a higher risk of developing T2D. The associations were independent of major risk factors for T2D, such as age, sex, race/ethnicity, socioeconomic characteristics, smoking status, physical activity, and obesity. What do these findings mean? The findings provide the first summary evidence to date for the positive relationships of concentrations of the DNL-related fatty acids with a risk of T2D, indicating the strong relevance of DNL and its determinants to the development of T2D. These fatty acids potentially reflect the status of DNL activity, which may be stimulated or suppressed by a combination of carbohydrate intake, alcohol intake, polyunsaturated fatty acid intake, and other lifestyle and clinical factors. Therefore, the current findings indicate the need for investigation into determinants and consequences of elevated concentrations of these fatty acids. Despite several advantages of our individual-level data analysis in this pooling project, the results cannot establish whether elevated concentrations of these fatty acids caused the development of T2D or whether underlying peripheral or hepatic insulin resistance, for example, may elevate both the fatty acid concentrations and the risk of T2D independently.
- Subjects :
- Male
Nutrition and Disease
Physiology
Type 2 diabetes
030204 cardiovascular system & hematology
Biochemistry
LEHA
Geographical locations
0302 clinical medicine
Endocrinology
Mathematical and Statistical Techniques
Voeding en Ziekte
Medicine and Health Sciences
Macromolecular Structure Analysis
Medicine
030212 general & internal medicine
Prospective Studies
Prospective cohort study
Human Nutrition & Health
2. Zero hunger
chemistry.chemical_classification
RISK
Lipid Analysis
PLASMA
Incidence (epidemiology)
Incidence
Fatty Acids
Statistics
Humane Voeding & Gezondheid
General Medicine
ASSOCIATION
Middle Aged
Metaanalysis
Lipids
CANCER
3. Good health
Type 2 Diabetes
ADIPOSE-TISSUE
BETA-CELL TURNOVER
Lipogenesis
Physical Sciences
Endokrinologi och diabetes
COFFEE CONSUMPTION
Female
Metabolic Networks and Pathways
Research Article
Endocrine Disorders
BIOMARKERS
Endocrinology and Diabetes
Research and Analysis Methods
03 medical and health sciences
SDG 3 - Good Health and Well-being
Diabetes mellitus
Diabetes Mellitus
Life Science
Humans
CORONARY-HEART-DISEASE
Statistical Methods
Molecular Biology
Aged
VLAG
business.industry
Fatty acid
Biology and Life Sciences
medicine.disease
United States
PHOSPHOLIPIDS
Human nutrition
Metabolism
chemistry
Diabetes Mellitus, Type 2
Metabolic Disorders
North America
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
People and places
business
Dyslipidemia
Mathematics
Subjects
Details
- Language :
- English
- ISSN :
- 15491277 and 15491676
- Volume :
- 17
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS Medicine
- Accession number :
- edsair.doi.dedup.....c8d874c33a575758580f82113c71a3d1