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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

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 di... Full description

Journal Title: The American Journal of Clinical Nutrition 2018, Vol. 108(1), pp.163-173
Main Author: Papandreou, Christopher
Other Authors: 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
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ID: ISSN: 0002-9165 ; E-ISSN: 1938-3207 ; DOI: 10.1093/ajcn/nqy058
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recordid: oxford10.1093/ajcn/nqy058
title: Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial
format: Article
creator:
  • 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
subjects:
  • Trimethylamine - N - Oxide
  • Metabolites
  • Type 2 Diabetes
  • Case - Cohort
  • Mediterranean Diet
  • Predimed
ispartof: The American Journal of Clinical Nutrition, 2018, Vol. 108(1), pp.163-173
description: 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 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.
language:
source:
identifier: ISSN: 0002-9165 ; E-ISSN: 1938-3207 ; DOI: 10.1093/ajcn/nqy058
fulltext: fulltext
issn:
  • 0002-9165
  • 00029165
  • 1938-3207
  • 19383207
url: Link


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titlePlasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial
creatorPapandreou, 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
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subjectTrimethylamine - N - Oxide ; Metabolites ; Type 2 Diabetes ; Case - Cohort ; Mediterranean Diet ; Predimed
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descriptionABSTRACT 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.
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authorPapandreou, 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
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