Journal
AMERICAN JOURNAL OF CLINICAL NUTRITION
Volume 108, Issue 1, Pages 163-173Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ajcn/nqy058
Keywords
trimethylamine-N-oxide; metabolites; type 2 diabetes; case-cohort; Mediterranean diet; PREDIMED
Categories
Funding
- NIH [R01-DK-102896]
- official funding agency for biomedical research of the Spanish government
- Instituto de Salud Carlos III [RTIC G03/140]
- Instituto de Salud Carlos III through the Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion
- Centro Nacional de Investigaciones Cardiovasculares [CNIC 06/2007]
- Fondo de Investigacion Sanitaria Fondo Europeo de Desarrollo Regional [PI04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505, PI13/00462]
- Ministerio de Ciencia e Innovacion [AGL-2009-13906-C02, AGL2010-22319-C03]
- Fundacion Mapfre, Consejeria de Salud de la Junta de Andalucia [PI0105/2007]
- Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana [ACOMP06109, GVA-COMP2010-181, GVACOMP2011-151, CS2010-AP-111, CS2011-AP-042]
- Regional Government of Navarra [P27/2011]
- Autonomous Government of Catalonia (PERIS 2016-2020
- Incorporacio de Cientifics I Tecnolegs) [SLT002/0016/00428]
- Lilly Foundation European Association of Diabetes (EASD) through the Institut d'Investigacions Sanitaries Pere i Virgili (IISPV), Tarragona, Spain
- Fundacion Patrimonio Comunal Olivarero and Hojiblanca (Malaga, Spain)
- California Walnut Commission (Sacramento, California)
- Borges (Reus, Spain)
- Morella Nuts (Reus, Spain)
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK102896] Funding Source: NIH RePORTER
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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.
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