Dataset Information

Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevencion con Dieta Mediterranea (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 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, ?-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 ?-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.

SUBMITTER: Papandreou C

PROVIDER: S-EPMC6862602 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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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 C Bulló Mònica M Zheng Yan Y Ruiz-Canela Miguel M Yu Edward E Guasch-Ferré Marta M Toledo Estefanía E Clish Clary C Corella Dolores D Estruch Ramon R Ros Emilio E Fitó Montserrat M Arós Fernando F Fiol Miquel M Lapetra José J Serra-Majem Lluís L Gómez-Gracia Enrique E Liang Liming L Fragkiadakis Georgios A GA Razquin Cristina C Hu Frank B FB Salas-Salvadó Jordi J

The American journal of clinical nutrition 20180701 1

<h4>Background</h4>The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial.<h4>Objective</h4>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.<h4>Design</h4>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 no ...[more]

PMID: 29982310

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