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Diabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels
Open accessAbstract
Recent studies have revealed strong associations between systemic trimethylamine N-oxide (TMAO) levels, atherosclerosis and cardiovascular risk. In addition, plasma L-carnitine levels in patients with high TMAO concentrations predicted an increased risk for cardiovascular disease and incident major adverse cardiac events. The aim of the present study was to investigate the relation between TMAO and L-carnitine plasma levels and diabetes. Blood plasma samples were collected from 12 and 20 weeks old db/db mice and patients undergoing percutaneous coronary intervention. Diabetic compared to non-diabetic db/L mice presented 10-fold higher TMAO, but lower L-carnitine plasma concentrations at 12 weeks of age. After 8 weeks of observation, diabetic db/db mice had significantly increased body weight, insulin resistance and TMAO concentration in comparison to non-diabetic control. In 191 patients undergoing percutaneous coronary intervention the median (interquartile range) plasma concentration of TMAO was 1.8 (1.2-2.6) µmol/L. Analysis of the samples showed a bivariate association of TMAO level with age, total cholesterol and L-carnitine. The multivariate linear regression analysis revealed that, in addition to L-carnitine as the strongest predictor of log transformed TMAO (p<0.001), the parameters of age, diabetes status and body mass index (BMI) were independently associated with increased log transformed TMAO levels (p<0.01).Our data provide evidence that age, diabetes and BMI are associated with higher TMAO levels independently of L-carnitine. These data support the hypothesis of TMAO as a cardiovascular risk marker and warrant further investigation of TMAO for diabetes research applications.
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“Differences in characteristics and disease status of participants across studies might affect TMAO levels14, 27, 28 and therefore partly explain such inconsistency.”
From Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta‐Analysis of Prospective Studies (2017) · cites this paper as [27]
In the citing paper
“In a group of 191 patients undergoing coronary intervention, plasma TMAO concentrations were independently associated with the patients' age, diabetes, and body mass index (35).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [35]
In the citing paper
“Vascular TF promotes thrombosis and vascular inflammation123, particularl y in patients with type 2 diabetes who have higher levels of circulating TMAO124–126.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [126]
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Citations
Cites
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,400
Prediabetes: a high-risk state for diabetes development
Tabák, A. G., Herder, C., Rathmann, W., Brunner, E. J., & Kivimäki, M. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60283-9 · Cited by 2,958
Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes
and the WHO Multinational Study Group, Morrish, N. J., Wang, S.-L., Stevens, L. K., Fuller, J. H., & Keen, H. (2001) · Diabetologia · doi:10.1007/pl00002934 · Cited by 1,288
Bennett, B. J., Vallim, T. Q. D. A., Wang, Z., Shih, D. M., Meng, Y., Gregory, J., Allayee, H., Lee, R., Graham, M., Crooke, R., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.011 · Cited by 1,070
Wang, Z., Tang, W. H. W., Buffa, J. A., Fu, X., Britt, E. B., Koeth, R. A., Levison, B. S., Fan, Y., Wu, Y., & Hazen, S. L. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu002 · Cited by 559
Intestinal microbiota, diet and health
Power, S. E., O'Toole, P. W., Stanton, C., Ross, R. P., & Fitzgerald, G. F. (2014) · British Journal Of Nutrition · doi:10.1017/s0007114513002560 · Cited by 476
Kinetics, Pharmacokinetics, and Regulation of l‐Carnitine and Acetyl‐l‐carnitine Metabolism
Rebouche, C. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1320.003 · Cited by 426
Molecular enzymology of carnitine transfer and transport
Ramsay, R. R., Gandour, R. D., & van der Leij, F. R. (2001) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(01)00147-9 · Cited by 395
Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet
Gao, X., Liu, X., Xu, J., Xue, C., Xue, Y., & Wang, Y. (2014) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2014.03.001 · Cited by 360
TMAO: A small molecule of great expectations
Ufnal, M., Żądło‐Dobrowolska, A., & Ostaszewski, R. (2015) · Nutrition · doi:10.1016/j.nut.2015.05.006 · Cited by 327
Wang, Z., Levison, B. S., Hazen, J. E., Donahue, L., Li, X.-M., & Hazen, S. L. (2014) · Analytical Biochemistry · doi:10.1016/j.ab.2014.03.016 · Cited by 320
Miller, C. A., Corbin, K. D., da Costa, K.-A., Zhang, S., Zhao, X., Galanko, J. A., Blevins, T., Bennett, B. J., O’Connor, A., & Zeisel, S. H. (2014) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.114.087692 · Cited by 240
Lever, M., George, P. M., Slow, S., Bellamy, D., Young, J. M., Ho, M., McEntyre, C. J., Elmslie, J. L., Atkinson, W., Molyneux, S. L., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114969 · Cited by 223
Endoplasmic Reticulum Stress Plays a Key Role in the Pathogenesis of Diabetic Peripheral Neuropathy
Lupachyk, S., Watcho, P., Stavniichuk, R., Shevalye, H., & Obrosova, I. G. (2013) · Diabetes · doi:10.2337/db12-0716 · Cited by 189
Gut microbiota metabolism of l-carnitine and cardiovascular risk
Ussher, J. R., Lopaschuk, G. D., & Arduini, A. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.10.013 · Cited by 172
Lloyd, A. J., Favé, G., Beckmann, M., Lin, W., Tailliart, K., Xie, L., Mathers, J. C., & Draper, J. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.017921 · Cited by 130
Trimethylamine: Metabolic, Pharmacokinetic and Safety Aspects
Bain, M., Fornasini, G., & Evans, A. (2005) · Current Drug Metabolism · doi:10.2174/1389200054021807 · Cited by 98
Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk
Tang, W., Wang, Z., & Levison, B. S. (2013) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2013.06.007 · Cited by 88
Metabolic Effects of L-carnitine on Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis
Vidal‐Casariego, A., Peláez, R. B., Faedo, C. M., Calvo-Gracia, F., Valero-Zanuy, M. Á., Pérez, L. M. L., & Compés, C. C. (2013) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0033-1333688 · Cited by 85
Dambrova, M., Skapare‐Makarova, E., Konrade, I., Pugovics, O., Grinberga, S., Tirzite, D., Petrovska, R., Kalvins, I., & Liepins, E. (2013) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.135 · Cited by 63
Self-citationDisposition and Metabolite Kinetics of Oral L‐carnitine in Humans
Bain, M. A., Milne, R. W., & Evans, A. M. (2006) · The Journal of Clinical Pharmacology · doi:10.1177/0091270006292851 · Cited by 46
Risks and Benefits of Carnitine Supplementation in Diabetes
Dambrova, M., & Liepinsh, E. (2014) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0034-1390481 · Cited by 22
Self-citationEpidemiology of Cardiovascular Disease in Patients with Type 1 Diabetes: European Perspective
Matteucci, E., & Giampietro, O. (2014) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0034-1367062 · Cited by 14
Liepinsh, E., Skapare, E., Vavers, E., Konrāde, I., Strēle, I., Grı̄nberga, S., Pugovičs, O., & Dambrova, M. (2012) · Nutrition Research · doi:10.1016/j.nutres.2012.03.010 · Cited by 13
Self-citationTang, W. H. W., Allayee, H., Lusis, A. J., Roberts, R., McPherson, R., Wang, Z., Bennett, B. J., Stewart, A. F. R., Hartiala, J., & Hazen, S. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/r6hc-3s06 · Cited by 6
Zhao, X., Galanko, J. A., Blevins, T., Miller, C. A., Zeisel, S. H., Zhang, S., O’Connor, A., Bennett, B. J., Costa, K. A. D., & Corbin, K. D. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/jwwk-yp40 · Cited by 4
Alberti (1998) · doi:10.1002/(sici)1096-9136(199807)15:7
Research works printed but not linked: 3
- Grinberga S, Dambrova M, Latkovskis G et al. Determination of trimeth- ylamine-N-oxide in combination with l-carnitine and γ-butyrobetaine in human plasma by UPLC/MS/MS. Biomed Chromatogr 2015; 29: 1670-1674
- Li X, Chen Y, Liu J et al. Serum metabolic variables associated with impaired glucose tolerance induced by high-fat-high-cholesterol diet in Macaca mulatta. Exp Biol Med (Maywood) 2012; 237: 1310-1321
- McEntyre CJ, Lever M, Chambers ST et al. Variation of betaine, N,N- dimethylglycine, choline, glycerophosphorylcholine, taurine and tri- methylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period. Ann Clin Biochem 2015; 52: 352-360
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Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051
Nogal, A., Valdes, A. M., & Menni, C. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1897212 · Cited by 917
Schwingshackl, L., Hoffmann, G., Lampousi, A.-M., Knüppel, S., Iqbal, K., Schwedhelm, C., Bechthold, A., Schlesinger, S., & Boeing, H. (2017) · European Journal of Epidemiology · doi:10.1007/s10654-017-0246-y · Cited by 799
Yang, W., & Cong, Y. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00661-4 · Cited by 715
Heianza, Y., Ma, W., Manson, J. E., Rexrode, K. M., & Qi, L. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.004947 · Cited by 544
Metadata
- Authors
- Dambrova, M., Latkovskis, G., Kuka, J., Strele, I., Konrade, I., Grinberga, S., Hartmane, D., Pugovics, O., Erglis, A., & Liepinsh, E.
- Affiliations
- Latvijas Organiskās Sintēzes Institūts (LV)
- Pauls Stradiņš Clinical University Hospital (LV)
- Riga Stradins University, Riga, Latvia
- Latvian Institute of Organic Synthesis, Riga, Latvia
- Paul Stradins Clinical University Hospital, Riga, Latvia
- Corresponding author
- Dambrova, M.
- Venue
- Experimental and Clinical Endocrinology & Diabetes
- Publisher
- Georg Thieme Verlag KG
- Published
- 2016-04-28
- Volume
- 124
- Issue
- 04
- Pages
- 251-256
- ISSN
- 0947-7349 (ISSN-L)
- 1439-3646
- OpenAlex
- W2342504128
- Cited by
- 229
- References
- 29
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 24 · 2023: 20 · 2022: 31 · 2021: 30 · 2020: 22 · 2019: 25 · 2018: 25 · 2017: 18 · 2016: 4
- FWCI
- 24.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Experimental and Clinical Endocrinology & Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- trimethylamine N-oxide, diabetes mellitus, L-carnitine, db/db mice, insulin resistance, cardiovascular risk markers, percutaneous coronary intervention, body mass index, age, atherosclerosis, plasma biomarkers
- MeSH terms
- Age Factors, Aged, Animals, Cardiovascular Diseases, Carnitine, Diabetes Mellitus, Disease Models, Animal, Female, Humans, Male, Methylamines, Middle Aged, Body Mass Index, Mice
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