Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case-Cohort Study

Overview

Journal Clin Chem

Publisher Oxford University Press

Specialty Biochemistry

Date 2018 Jun 10

PMID 29884676

Citations 48

Authors

Edward Yu

Christopher Papandreou

Miguel Ruiz-Canela

Marta Guasch-Ferre

Clary B Clish

Courtney Dennis

Liming Liang

Dolores Corella

Montserrat Fito

Cristina Razquin

Jose Lapetra

Ramon Estruch

Emilio Ros

Montserrat Cofan

Fernando Aros

Estefania Toledo

Lluis Serra-Majem

Jose V Sorli

Frank B Hu

Miguel A Martinez-Gonzalez

Jordi Salas-Salvado

Affiliations

Soon will be listed here.

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.

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