Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial

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Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial. / Papandreou, Christopher; Bulló, Mònica; Zheng, Yan; Ruiz-Canela, Miguel; Yu, Edward; Guasch-Ferré, Marta; Toledo, Estefanía; Clish, Clary; Corella, Dolores; Estruch, Ramon; Ros, Emilio; Fitó, Montserrat; Arós, Fernando; Fiol, Miquel; Lapetra, José; Serra-Majem, Lluís; Gómez-Gracia, Enrique; Liang, Liming; Fragkiadakis, Georgios A.; Razquin, Cristina; Hu, Frank B.; Salas-Salvadó, Jordi.

In: American Journal of Clinical Nutrition, Vol. 108, No. 1, 2018, p. 163-173.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Papandreou, C, Bulló, M, Zheng, Y, Ruiz-Canela, M, Yu, E, Guasch-Ferré, M, Toledo, E, Clish, C, Corella, D, Estruch, R, Ros, E, Fitó, M, Arós, F, Fiol, M, Lapetra, J, Serra-Majem, L, Gómez-Gracia, E, Liang, L, Fragkiadakis, GA, Razquin, C, Hu, FB & Salas-Salvadó, J 2018, 'Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial', American Journal of Clinical Nutrition, vol. 108, no. 1, pp. 163-173. https://doi.org/10.1093/ajcn/nqy058

APA

Papandreou, C., Bulló, M., Zheng, Y., Ruiz-Canela, M., Yu, E., Guasch-Ferré, M., Toledo, E., Clish, C., Corella, D., Estruch, R., Ros, E., Fitó, M., Arós, F., Fiol, M., Lapetra, J., Serra-Majem, L., Gómez-Gracia, E., Liang, L., Fragkiadakis, G. A., ... Salas-Salvadó, J. (2018). Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial. American Journal of Clinical Nutrition, 108(1), 163-173. https://doi.org/10.1093/ajcn/nqy058

Vancouver

Papandreou C, Bulló M, Zheng Y, Ruiz-Canela M, Yu E, Guasch-Ferré M et al. Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial. American Journal of Clinical Nutrition. 2018;108(1):163-173. https://doi.org/10.1093/ajcn/nqy058

Author

Papandreou, Christopher ; Bulló, Mònica ; Zheng, Yan ; Ruiz-Canela, Miguel ; Yu, Edward ; Guasch-Ferré, Marta ; Toledo, Estefanía ; Clish, Clary ; Corella, Dolores ; Estruch, Ramon ; Ros, Emilio ; Fitó, Montserrat ; Arós, Fernando ; Fiol, Miquel ; Lapetra, José ; Serra-Majem, Lluís ; Gómez-Gracia, Enrique ; Liang, Liming ; Fragkiadakis, Georgios A. ; Razquin, Cristina ; Hu, Frank B. ; Salas-Salvadó, Jordi. / Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial. In: American Journal of Clinical Nutrition. 2018 ; Vol. 108, No. 1. pp. 163-173.

Bibtex

@article{7b640f3d8a0d40c9b9ad85d131a612cc,
title = "Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevenci{\'o}n con Dieta Mediterr{\'a}nea (PREDIMED) trial",
abstract = "Background The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial. Objective The aim of this study was to investigate associations between TMAO and related metabolites with T2D risk in subjects at high risk of cardiovascular disease. Design This is a case-cohort design study within the Prevenci{\'o}n con Dieta Mediterr{\'a}nea (PREDIMED) study, with 251 incident T2D cases and a random sample of 694 participants (641 noncases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 y). We used liquid chromatography-tandem mass spectrometry to measure plasma TMAO, l-carnitine, betaine, lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) species, phosphocholine, α-glycerophosphocholine, and choline at baseline and after 1 y. We examined associations with the use of weighted Cox proportional hazard models, accounting for the weighted case-cohort design by the Barlow method. Results After adjustment for recognized T2D risk factors and multiple testing, individuals in the highest quartile of baseline TMAO and α-glycerophosphocholine had a lower risk of T2D [HR (95% CI): 0.52 (0.29, 0.89) and 0.46 (0.24, 0.89), respectively]. The HR (95% CI) comparing the extreme quartiles of betaine was 0.41 (0.23, 0.74). Similar trends were observed for C16:0 LPC, C18:1 LPC, C18:0 LPC, C20:4 LPC, C22:6 LPC, C18:1 LPC plasmalogen, and C16:0 LPE. After correcting for multiple comparisons, participants in the highest quartile of 1-y changes in oleic acid LPC plasmalogen concentrations had a lower T2D risk than the reference quartile. Conclusion Whether the associations between plasma TMAO and certain metabolite concentrations with T2D risk reflect its pathophysiology or represent an epiphenomenon needs to be elucidated. This trial is registered at http://www.controlled-trials.com as ISRCTN35739639.",
keywords = "case-cohort, Mediterranean diet, metabolites, PREDIMED, trimethylamine-N-oxide, type 2 diabetes",
author = "Christopher Papandreou and M{\`o}nica Bull{\'o} and Yan Zheng and Miguel Ruiz-Canela and Edward Yu and Marta Guasch-Ferr{\'e} and Estefan{\'i}a Toledo and Clary Clish and Dolores Corella and Ramon Estruch and Emilio Ros and Montserrat Fit{\'o} and Fernando Ar{\'o}s and Miquel Fiol and Jos{\'e} Lapetra and Llu{\'i}s Serra-Majem and Enrique G{\'o}mez-Gracia and Liming Liang and Fragkiadakis, {Georgios A.} and Cristina Razquin and Hu, {Frank B.} and Jordi Salas-Salvad{\'o}",
note = "Publisher Copyright: {\textcopyright} 2018 American Society for Nutrition.",
year = "2018",
doi = "10.1093/ajcn/nqy058",
language = "English",
volume = "108",
pages = "163--173",
journal = "American Journal of Clinical Nutrition",
issn = "0002-9165",
publisher = "American Society for Nutrition",
number = "1",

}

RIS

TY - JOUR

T1 - Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial

AU - Papandreou, Christopher

AU - Bulló, Mònica

AU - Zheng, Yan

AU - Ruiz-Canela, Miguel

AU - Yu, Edward

AU - Guasch-Ferré, Marta

AU - Toledo, Estefanía

AU - Clish, Clary

AU - Corella, Dolores

AU - Estruch, Ramon

AU - Ros, Emilio

AU - Fitó, Montserrat

AU - Arós, Fernando

AU - Fiol, Miquel

AU - Lapetra, José

AU - Serra-Majem, Lluís

AU - Gómez-Gracia, Enrique

AU - Liang, Liming

AU - Fragkiadakis, Georgios A.

AU - Razquin, Cristina

AU - Hu, Frank B.

AU - Salas-Salvadó, Jordi

N1 - Publisher Copyright: © 2018 American Society for Nutrition.

PY - 2018

Y1 - 2018

N2 - Background The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial. Objective The aim of this study was to investigate associations between TMAO and related metabolites with T2D risk in subjects at high risk of cardiovascular disease. Design This is a case-cohort design study within the Prevención con Dieta Mediterránea (PREDIMED) study, with 251 incident T2D cases and a random sample of 694 participants (641 noncases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 y). We used liquid chromatography-tandem mass spectrometry to measure plasma TMAO, l-carnitine, betaine, lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) species, phosphocholine, α-glycerophosphocholine, and choline at baseline and after 1 y. We examined associations with the use of weighted Cox proportional hazard models, accounting for the weighted case-cohort design by the Barlow method. Results After adjustment for recognized T2D risk factors and multiple testing, individuals in the highest quartile of baseline TMAO and α-glycerophosphocholine had a lower risk of T2D [HR (95% CI): 0.52 (0.29, 0.89) and 0.46 (0.24, 0.89), respectively]. The HR (95% CI) comparing the extreme quartiles of betaine was 0.41 (0.23, 0.74). Similar trends were observed for C16:0 LPC, C18:1 LPC, C18:0 LPC, C20:4 LPC, C22:6 LPC, C18:1 LPC plasmalogen, and C16:0 LPE. After correcting for multiple comparisons, participants in the highest quartile of 1-y changes in oleic acid LPC plasmalogen concentrations had a lower T2D risk than the reference quartile. Conclusion Whether the associations between plasma TMAO and certain metabolite concentrations with T2D risk reflect its pathophysiology or represent an epiphenomenon needs to be elucidated. This trial is registered at http://www.controlled-trials.com as ISRCTN35739639.

AB - Background The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial. Objective The aim of this study was to investigate associations between TMAO and related metabolites with T2D risk in subjects at high risk of cardiovascular disease. Design This is a case-cohort design study within the Prevención con Dieta Mediterránea (PREDIMED) study, with 251 incident T2D cases and a random sample of 694 participants (641 noncases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 y). We used liquid chromatography-tandem mass spectrometry to measure plasma TMAO, l-carnitine, betaine, lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) species, phosphocholine, α-glycerophosphocholine, and choline at baseline and after 1 y. We examined associations with the use of weighted Cox proportional hazard models, accounting for the weighted case-cohort design by the Barlow method. Results After adjustment for recognized T2D risk factors and multiple testing, individuals in the highest quartile of baseline TMAO and α-glycerophosphocholine had a lower risk of T2D [HR (95% CI): 0.52 (0.29, 0.89) and 0.46 (0.24, 0.89), respectively]. The HR (95% CI) comparing the extreme quartiles of betaine was 0.41 (0.23, 0.74). Similar trends were observed for C16:0 LPC, C18:1 LPC, C18:0 LPC, C20:4 LPC, C22:6 LPC, C18:1 LPC plasmalogen, and C16:0 LPE. After correcting for multiple comparisons, participants in the highest quartile of 1-y changes in oleic acid LPC plasmalogen concentrations had a lower T2D risk than the reference quartile. Conclusion Whether the associations between plasma TMAO and certain metabolite concentrations with T2D risk reflect its pathophysiology or represent an epiphenomenon needs to be elucidated. This trial is registered at http://www.controlled-trials.com as ISRCTN35739639.

KW - case-cohort

KW - Mediterranean diet

KW - metabolites

KW - PREDIMED

KW - trimethylamine-N-oxide

KW - type 2 diabetes

U2 - 10.1093/ajcn/nqy058

DO - 10.1093/ajcn/nqy058

M3 - Journal article

C2 - 29982310

AN - SCOPUS:85050810414

VL - 108

SP - 163

EP - 173

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 1

ER -

ID: 358091239