Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case-Cohort Study.
Title | Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case-Cohort Study. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Yu, E., Papandreou C., Ruiz-Canela M., Guasch-Ferré M., Clish C. B., Dennis C., Liang L., Corella D., Fitó M., Razquin C., Lapetra J., Estruch R., Ros E., Cofán M., Arós F., Toledo E., Serra-Majem L., Sorli J. V., Hu F. B., Martínez-González M. A., & Salas-Salvadó J. |
Journal | Clin Chem |
Volume | 64 |
Issue | 8 |
Pagination | 1211-1220 |
Date Published | 2018 Aug |
ISSN | 1530-8561 |
Abstract | BACKGROUND: 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. |
DOI | 10.1373/clinchem.2018.288720 |
Alternate Journal | Clin. Chem. |
PubMed ID | 29884676 |