Plasma Trimethylamine-N-oxide and impaired glucose regulation: Results from The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)


Autoři: Sumith Roy aff001;  Melana Yuzefpolskaya aff002;  Renu Nandakumar aff003;  Paolo C. Colombo aff002;  Ryan T. Demmer aff001
Působiště autorů: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States of America aff001;  Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York, NY, United States of America aff002;  Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY, United States of America aff003;  Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States of America aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227482

Souhrn

Trimethylamine-N-oxide (TMAO)–a gut-microbiota metabolite–is a biomarker of cardiometabolic risk. No studies have investigated TMAO as an early biomarker of longitudinal glucose increase or prevalent impaired glucose regulation. In a longitudinal cohort study, 300 diabetes-free men and women (77%) aged 20–55 years (mean = 34±10) were enrolled at baseline and re-examined at 2-years to investigate the association between TMAO and biomarkers of diabetes risk. Plasma TMAO was measured using Ultra Performance Liquid Chromatography-Mass Spectrometry. After an overnight fast, FPG was measured longitudinally, HbA1C and insulin were measured only at baseline. Insulin resistance was defined using HOMA-IR. Multivariable generalized linear models regressed; i) FPG change (year 2 minus baseline) on baseline TMAO tertiles; and ii) HOMA-IR and HbA1c on TMAO tertiles. Multivariable relative risk regressions modeled prevalent prediabetes across TMAO tertiles. Mean values of 2-year longitudinal FPG±SE across tertiles of TMAO were 86.6±0.9, 86.7±0.9, 86.4±0.9 (p = 0.98). Trends were null for FPG, HbA1c, HOMA-IR, cross-sectionally. The prevalence ratio of prediabetes among participants in 2nd and 3rd TMAO tertiles (vs. the 1st) were 1.94 [95%CI 1.09–3.48] and 1.41 [95%CI: 0.76–2.61]. TMAO levels are associated with increased prevalence of prediabetes in a nonlinear fashion but not with insulin resistance or longitudinal FPG change.

Klíčová slova:

Biomarkers – Blood plasma – Diabetes mellitus – Glucose – HbA1c – Insulin resistance – Renal system – Type 2 diabetes


Zdroje

1. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States. Atlanta, GA: Centers for Disease Control and Prevention, 2014.

2. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541–6. doi: 10.1038/nature12506 23985870.

3. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature medicine. 2013;19(5):576–85. Epub 2013/04/09. doi: 10.1038/nm.3145 23563705; PubMed Central PMCID: PMC3650111.

4. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63. Epub 2011/04/09. doi: 10.1038/nature09922 21475195; PubMed Central PMCID: PMC3086762.

5. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. The New England journal of medicine. 2013;368(17):1575–84. Epub 2013/04/26. doi: 10.1056/NEJMoa1109400 23614584; PubMed Central PMCID: PMC3701945.

6. Gao X, Liu X, Xu J, Xue C, Xue Y, Wang Y. Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet. Journal of bioscience and bioengineering. 2014;118(4):476–81. Epub 2014/04/12. doi: 10.1016/j.jbiosc.2014.03.001 24721123.

7. Miao J, Ling AV, Manthena PV, Gearing ME, Graham MJ, Crooke RM, et al. Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis. Nature communications. 2015;6:6498. Epub 2015/04/08. doi: 10.1038/ncomms7498 25849138; PubMed Central PMCID: PMC4391288.

8. Tang WH, Wang Z, Fan Y, Levison B, Hazen JE, Donahue LM, et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014;64(18):1908–14. Epub 2014/12/03. doi: 10.1016/j.jacc.2014.02.617 25444145; PubMed Central PMCID: PMC4254529.

9. Shan Z, Sun T, Huang H, Chen S, Chen L, Luo C, et al. Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes. The American journal of clinical nutrition. 2017;106(3):888–94. Epub 2017/07/21. doi: 10.3945/ajcn.117.157107 28724646.

10. Dambrova M, Latkovskis G, Kuka J, Strele I, Konrade I, Grinberga S, et al. Diabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels. Exp Clin Endocrinol Diabetes. 2016;124(4):251–6. Epub 2016/04/29. doi: 10.1055/s-0035-1569330 27123785.

11. Lever M, George PM, Slow S, Bellamy D, Young JM, Ho M, et al. Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study. PLoS One. 2014;9(12):e114969. Epub 2014/12/11. doi: 10.1371/journal.pone.0114969 25493436; PubMed Central PMCID: PMC4262445.

12. Papandreou C, Bullo M, Zheng Y, Ruiz-Canela M, Yu E, Guasch-Ferre M, et al. Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevencion con Dieta Mediterranea (PREDIMED) trial. The American journal of clinical nutrition. 2018;108(1):163–73. doi: 10.1093/ajcn/nqy058 29982310.

13. Demmer RT, Jacobs DR Jr., Singh R, Zuk A, Rosenbaum M, Papapanou PN, et al. Periodontal Bacteria and Prediabetes Prevalence in ORIGINS: The Oral Infections, Glucose Intolerance, and Insulin Resistance Study. Journal of dental research. 2015;94(9 Suppl):201s–11s. Epub 2015/06/18. doi: 10.1177/0022034515590369 26082387; PubMed Central PMCID: PMC4547206.

14. Wang Z, Levison BS, Hazen JE, Donahue L, Li XM, Hazen SL. Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry. Analytical biochemistry. 2014;455:35–40. Epub 2014/04/08. doi: 10.1016/j.ab.2014.03.016 24704102; PubMed Central PMCID: PMC4167037.

15. Demmer RT, Breskin A, Rosenbaum M, Zuk A, LeDuc C, Leibel R, et al. The Subgingival Microbiome, Systemic Inflammation and Insulin Resistance: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS). J Clin Periodontol. 2016. doi: 10.1111/jcpe.12664 27978598.

16. Demmer RT, Jacobs DR Jr., Singh R, Zuk A, Rosenbaum M, Papapanou PN, et al. Periodontal Bacteria and Prediabetes Prevalence in ORIGINS: The Oral Infections, Glucose Intolerance, and Insulin Resistance Study. J Dent Res. 2015. doi: 10.1177/0022034515590369 26082387.

17. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9. Epub 1985/07/01. doi: 10.1007/bf00280883 3899825.

18. Demmer RT, Squillaro A, Papapanou PN, Rosenbaum M, Friedewald WT, Jacobs DR Jr., et al. Periodontal Infection, Systemic Inflammation, and Insulin Resistance: Results from the Continuous National Health and Nutrition Examination Survey (NHANES) 1999–2004. Diabetes Care. 2012;35(11):2235–42. Epub 2012/07/28. doi: 10.2337/dc12-0072 22837370.

19. Diagnosis and classification of diabetes mellitus. Diabetes care. 2014;37 Suppl 1:S81–90. Epub 2013/12/21. doi: 10.2337/dc14-S081 24357215.

20. Ainsworth BE, Haskell WL, Leon AS, Jacobs DR Jr., Montoye HJ, Sallis JF, et al. Compendium of physical activities: classification of energy costs of human physical activities. Medicine and science in sports and exercise. 1993;25(1):71–80. Epub 1993/01/01. doi: 10.1249/00005768-199301000-00011 8292105.

21. Thai A, Papapanou PN, Jacobs DR Jr., Desvarieux M, Demmer RT. Periodontal infection and cardiorespiratory fitness in younger adults: results from continuous national health and nutrition examination survey 1999–2004. PLoS One. 2014;9(3):e92441. doi: 10.1371/journal.pone.0092441 24663097; PubMed Central PMCID: PMC3963905.

22. Chiuve SE, Fung TT, Rimm EB, Hu FB, McCullough ML, Wang M, et al. Alternative dietary indices both strongly predict risk of chronic disease. J Nutr. 2012;142(6):1009–18. doi: 10.3945/jn.111.157222 22513989; PubMed Central PMCID: PMC3738221.

23. McCullough ML, Feskanich D, Stampfer MJ, Giovannucci EL, Rimm EB, Hu FB, et al. Diet quality and major chronic disease risk in men and women: moving toward improved dietary guidance. The American journal of clinical nutrition. 2002;76(6):1261–71. Epub 2002/11/27. doi: 10.1093/ajcn/76.6.1261 12450892.

24. Tang WH, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116(3):448–55. Epub 2015/01/20. doi: 10.1161/CIRCRESAHA.116.305360 25599331; PubMed Central PMCID: PMC4312512.

25. Meyer KA, Benton TZ, Bennett BJ, Jacobs DR Jr., Lloyd-Jones DM, Gross MD, et al. Microbiota-Dependent Metabolite Trimethylamine N-Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA). Journal of the American Heart Association. 2016;5(10). Epub 2016/10/30. doi: 10.1161/jaha.116.003970 27792658; PubMed Central PMCID: PMC5121500.


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