Yu, EdwardPapandreou, ChristopherRuiz-Canela, MiguelGuasch-Ferre, MartaClish, Clary BDennis, CourtneyLiang, LimingCorella, DoloresFitó, MontserratRazquin, CristinaLapetra, JoséEstruch, RamónRos, EmilioCofán, MontserratArós, FernandoToledo, EstefaniaSerra-Majem, LluisSorlí, José VHu, Frank BMartinez-Gonzalez, Miguel ASalas-Salvado, Jordi2023-01-252023-01-252018-06-08http://hdl.handle.net/10668/12567Metabolites 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). 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. 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. 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.enCase-Control StudiesCohort StudiesDiabetes Mellitus, Type 2FemaleHomeostasisHumansInsulin ResistanceMaleTryptophanresearch article29884676open access10.1373/clinchem.2018.2887201530-8561PMC6218929https://academic.oup.com/clinchem/article-pdf/64/8/1211/32643097/clinchem1211.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218929/pdf