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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

Autores: Papandreou, C. ; Bullo, M. (Autor de correspondencia); Zheng, Y. ; Ruiz-Canela, Miguel; Yu, E.; Guasch-Ferre, M. ; Toledo Atucha, Estefanía; Clish, C.; Estruch, R.; Ros, E.; Fito, M.; Aros, F. ; Fiol, M. ; Lapetra, J. ; Serra-Majem, L.; Gomez-Gracia, E. ; Liang, L. M.; Fragkiadakis, G. A.; Razquin Burillo, Cristina; Hu, F. B.; Salas-Salvado, J. (Autor de correspondencia)
ISSN: 0002-9165
Volumen: 108
Número: 1
Páginas: 163 - 173
Fecha de publicación: 2018
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 Prevencion con Dieta Mediterranea (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, a-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 a-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.