%0 Journal Article
%A Yu, Edward
%A Papandreou, Christopher
%A Ruiz-Canela, Miguel
%A Guasch-Ferre, Marta
%A Clish, Clary B
%A Dennis, Courtney
%A Liang, Liming
%A Corella, Dolores
%A Fitó, Montserrat
%A Razquin, Cristina
%A Lapetra, José
%A Estruch, Ramón
%A Ros, Emilio
%A Cofán, Montserrat
%A Arós, Fernando
%A Toledo, Estefania
%A Serra-Majem, Lluis
%A Sorlí, José V
%A Hu, Frank B
%A Martinez-Gonzalez, Miguel A
%A Salas-Salvado, Jordi
%T Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case-Cohort Study.
%D 2018
%U http://hdl.handle.net/10668/12567
%X 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). 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.
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