6533b7d9fe1ef96bd126cc59

RESEARCH PRODUCT

Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial

Enrique Gómez-graciaClary B. ClishEstefanía ToledoEstefanía ToledoFernando ArósMònica BullóMònica BullóCristina RazquinCristina RazquinLluis Serra-majemLluis Serra-majemEdward YuJordi Salas-salvadóJordi Salas-salvadóMiquel FiolMarta Guasch-ferréMarta Guasch-ferréMarta Guasch-ferréYan ZhengDolores CorellaDolores CorellaLiming LiangMiguel Ruiz-canelaMiguel Ruiz-canelaEmilio RosEmilio RosChristopher PapandreouChristopher PapandreouRamon EstruchRamon EstruchGeorgios A. FragkiadakisJosé LapetraMontserrat FitóFrank B. HuFrank B. Hu

subject

Male0301 basic medicinemedicine.medical_specialtyMedicine (miscellaneous)030209 endocrinology & metabolismTrimethylamine N-oxideType 2 diabetesDiet MediterraneanLower riskGastroenterologyCohort StudiesMethylamines03 medical and health scienceschemistry.chemical_compound0302 clinical medicineRisk FactorsDiabetes mellitusInternal medicineHumansNutsMedicineCholineAgedNutrition and Dieteticsbusiness.industryCase-control studyMiddle Agedmedicine.diseaseOriginal Research Communications030104 developmental biologyDiabetes Mellitus Type 2QuartilechemistryCase-Control StudiesFemalelipids (amino acids peptides and proteins)businessCohort study

description

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, 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.

yearjournalcountryeditionlanguage
2018-07-01The American Journal of Clinical Nutrition
https://doi.org/10.1093/ajcn/nqy058