Yu, EdwardPapandreou, ChristopherRuiz Canela, MiguelGuasch-Ferré, MartaClish, Clary B.Dennis, CourtneyLiang, LimingCorella Piquer, DoloresFitó Colomer, MontserratRazquin, CristinaLapetra, JoséEstruch Riba, RamonRos Rahola, EmilioCofán Pujol, MontserratArós, FernandoToledo Atucha, EstefaníaSerra Majem, LluísSorlí, José V.Hu, Frank B.Martínez-González, Miguel Ángel, 1957-Salas Salvadó, Jordi2020-04-242020-04-242018-08-012045-2322https://hdl.handle.net/2445/157462BACKGROUND: Metabolites of the tryptophan-kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case-cohort design nested in the Prevención con Dieta Mediterránea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). METHODS: Plasma metabolite concentrations were quantified via LC-MS for n = 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. RESULTS: Baseline tryptophan was associated with higher risk of incident T2D (hazard ratio = 1.29; 95% CI, 1.04-1.61 per SD). Positive changes in quinolinic acid from baseline to 1 year were associated with a higher risk of T2D (hazard ratio = 1.39; 95% CI, 1.09-1.77 per SD). Baseline tryptophan and kynurenic acid were directly associated with changes in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to 1 year. Concurrent changes in kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine/tryptophan ratio were associated with baseline-to-1-year changes in HOMA-IR. CONCLUSIONS: Baseline tryptophan and 1-year increases in quinolinic acid were positively associated with incident T2D. Baseline and 1-year changes in tryptophan metabolites predicted changes in HOMA-IR. Tryptophan levels may initially increase and then deplete as diabetes progresses in severity.19 p.application/pdfengcc-by (c) Yu, Edward et al., 2018http://creativecommons.org/licenses/by/3.0/esDiabetisEstudi de casosTriptòfanDiabetesCase studiesTryptophaninfo:eu-repo/semantics/article6876872020-04-24info:eu-repo/semantics/openAccess29884676