Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial.
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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. This trial is registered at http://www.controlled-trials.com as ISRCTN35739639. |
Year of Publication | 2018
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Journal | Am J Clin Nutr
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Volume | 108
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Issue | 1
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Pages | 163-173
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Date Published | 2018 07 01
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ISSN | 1938-3207
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DOI | 10.1093/ajcn/nqy058
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PubMed ID | 29982310
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PubMed Central ID | PMC6862602
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Grant list | P30 DK040561 / DK / NIDDK NIH HHS / United States
R01 DK102896 / DK / NIDDK NIH HHS / United States
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