RT Journal Article
T1 Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial.
A1 Papandreou, Christopher
A1 Bulló, Mònica
A1 Zheng, Yan
A1 Ruiz-Canela, Miguel
A1 Yu, Edward
A1 Guasch-Ferré, Marta
A1 Toledo, Estefanía
A1 Clish, Clary
A1 Corella, Dolores
A1 Estruch, Ramon
A1 Ros, Emilio
A1 Fitó, Montserrat
A1 Arós, Fernando
A1 Fiol, Miquel
A1 Lapetra, José
A1 Serra-Majem, Lluís
A1 Gómez-Gracia, Enrique
A1 Liang, Liming
A1 Fragkiadakis, Georgios A
A1 Razquin, Cristina
A1 Hu, Frank B
A1 Salas-Salvadó, Jordi
AB The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial. 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. 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. 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. 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.
YR 2018
FD 2018
LK http://hdl.handle.net/10668/12689
UL http://hdl.handle.net/10668/12689
LA en
DS RISalud
RD Jul 4, 2025