Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes
Open accessAbstract
Background: The association of trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary choline and carnitine, with type 2 diabetes was inconsistent.Objective: We evaluated the association of plasma TMAO with newly diagnosed type 2 diabetes and the potential modification of TMAO-generating enzyme flavin monooxygenase 3 (FMO3) polymorphisms.Design: This was an age- and sex-matched case-control study of 2694 participants: 1346 newly diagnosed cases of type 2 diabetes and 1348 controls. Concentrations of plasma TMAO were measured, and FMO3 E158K polymorphisms (rs2266782) were genotyped.Results: Medians (IQRs) of plasma TMAO concentration were 1.47 μmol/L (0.81-2.20 μmol/L) for controls and 1.77 μmol/L (1.09-2.80 μmol/L) for type 2 diabetes cases. From the lowest to the highest quartiles of plasma TMAO, the multivariable adjusted ORs of type 2 diabetes were 1.00 (reference), 1.38 (95% CI: 1.08, 1.77), 1.64 (95% CI: 1.28, 2.09), and 2.55 (95% CI: 1.99, 3.28) (P-trend < 0.001); each SD of ln-transformed plasma TMAO was associated with a 38% (95% CI: 26%, 51%) increment in ORs of type 2 diabetes. The FMO3 rs2266782 polymorphism was not associated with type 2 diabetes. The positive association between plasma TMAO and type 2 diabetes was consistent in each rs2266782 genotype group, and no significant interaction was observed (P = 0.093).Conclusions: Our results suggested that higher plasma TMAO was associated with increased odds of newly diagnosed type 2 diabetes and that this association was not modified by the FMO3 rs2266782 polymorphism. This study was registered at clinicaltrials.gov as NCT03130894.
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High levels of trimethylamine N-oxide have been associated with increased risk of cardiovascular disease and mortality.
“High levels of TMAO have been associated with increased risk of cardiovascular disease and mortality.143–145”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [143]
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- Authors
- Shan, Z., Sun, T., Huang, H., Chen, S., Chen, L., Luo, C., Yang, W., Yang, X., Yao, P., Cheng, J., Hu, F. B., & Liu, L.
- Affiliations
- Harvard University (US)
- Huazhong University of Science and Technology (CN)
- Shenzhen Center for Disease Control and Prevention (CN)
- Corresponding author
- Hu, Frank B
- Liu, Liegang
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 106
- Issue
- 3
- Pages
- 888-894
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2739043690
- Cited by
- 210
- References
- 11
- Citations by year
- 2026: 17 · 2025: 29 · 2024: 18 · 2023: 23 · 2022: 32 · 2021: 29 · 2020: 30 · 2019: 17 · 2018: 15
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- trimethylamine N-oxide, type 2 diabetes, gut microbiota, FMO3, flavin monooxygenase 3, choline metabolism, carnitine metabolism, plasma biomarkers, genetic susceptibility, newly diagnosed diabetes
- MeSH terms
- Gastrointestinal Microbiome, Adult, Carnitine, Choline, Diabetes Mellitus, Type 2, Female, Genotype, Humans, Intestinal Mucosa, Intestines, Male, Methylamines, Middle Aged, Oxides, Oxygenases, Polymorphism, Genetic, Odds Ratio, Case-Control Studies
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