Ruiz-Canela, MiguelGuasch-Ferré, MartaToledo, EstefaníaClish, Clary BRazquin, CristinaLiang, LimingWang, Dong DCorella, DoloresEstruch, RamónHernáez, ÁlvaroYu, EdwardGómez-Gracia, EnriqueZheng, YanArós, FernandoRomaguera, DoraDennis, CourtneyRos, EmilioLapetra, JoséSerra-Majem, LluisPapandreou, ChristopherPortoles, OlgaFitó, MontserratSalas-Salvadó, JordiHu, Frank BMartínez-González, Miguel A2023-01-252023-01-252018-04-16http://hdl.handle.net/10668/12358Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with type 2 diabetes. However, repeated measurements of BCAA/AAA and their interactions with dietary interventions have not been evaluated. We investigated the associations between baseline and changes at 1 year in BCAA/AAA with type 2 diabetes in the context of a Mediterranean diet (MedDiet) trial. We included 251 participants with incident type 2 diabetes and a random sample of 694 participants (641 participants without type 2 diabetes and 53 overlapping cases) in a case-cohort study nested within the PREvención con DIeta MEDiterránea (PREDIMED) trial. Participants were randomised to a MedDiet+extra-virgin olive oil (n = 273), a MedDiet+nuts (n = 324) or a control diet (n = 295). We used LC-MS/MS to measure plasma levels of amino acids. Type 2 diabetes was a pre-specified secondary outcome of the PREDIMED trial. Elevated plasma levels of individual BCAAs/AAAs were associated with higher type 2 diabetes risk after a median follow-up of 3.8 years: multivariable HR for the highest vs lowest quartile ranged from 1.32 for phenylalanine ([95% CI 0.90, 1.92], p for trend = 0.015) to 3.29 for leucine ([95% CI 2.03, 5.34], p for trend Our results support that higher baseline BCAAs and their increases at 1 year were associated with higher type 2 diabetes risk. A Mediterranean diet rich in extra-virgin olive oil significantly reduced the levels of BCAA and attenuated the positive association between plasma BCAA levels and type 2 diabetes incidence. Clinical trial number: SRCTN35739639 ( www.controlled-trials.com ).enAromatic amino acidsBranched-chain amino acidsMediterranean dietType 2 diabetesAgedAged, 80 and overAmino Acids, AromaticAmino Acids, Branched-ChainCase-Control StudiesDiabetes Mellitus, Type 2Diet, MediterraneanFemaleHumansIncidenceMaleMiddle AgedNutsOlive OilProtective FactorsRisk FactorsSpainTime FactorsTreatment OutcomeUp-Regulationresearch article29663011open access10.1007/s00125-018-4611-51432-0428PMC5988977https://link.springer.com/content/pdf/10.1007/s00125-018-4611-5.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988977/pdf