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Title: Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevencion con Dieta Mediterranea (PREDIMED) trial
Authors: 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, Lluis 
Gómez-Gracia, Enrique
Liang, Liming
Fragkiadakis, Georgios A.
Razquin, Cristina
Hu, Frank B.
Salas-Salvadó, Jordi
UNESCO Clasification: 3206 Ciencias de la nutrición
Keywords: Trimethylamine-N-oxide
Type 2 diabetes
Mediterranean diet, et al
Issue Date: 2018
Journal: The American journal of clinical nutrition 
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.
ISSN: 0002-9165
DOI: 10.1093/ajcn/nqy058
Source: American Journal of Clinical Nutrition [ISSN 0002-9165], v. 108 (1), p. 163-173
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