Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial: A case–cohort study
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Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial : A case–cohort study. / Yu, Edward; Papandreou, Christopher; Ruiz-Canela, Miguel; Guasch-Ferre, Marta; Clish, Clary B.; Dennis, Courtney; Liang, Liming; Corella, Dolores; Fitó, Montserrat; Razquin, Cristina; Lapetra, José; Estruch, Ramón; Ros, Emilio; Cofán, Montserrat; Arós, Fernando; Toledo, Estefania; Serra-Majem, Lluis; Sorlí, José V.; Hu, Frank B.; Martinez-Gonzalez, Miguel A.; Salas-Salvado, Jordi.
In: Clinical Chemistry, Vol. 64, No. 8, 2018, p. 1211-1220.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial
T2 - A case–cohort study
AU - Yu, Edward
AU - Papandreou, Christopher
AU - Ruiz-Canela, Miguel
AU - Guasch-Ferre, Marta
AU - Clish, Clary B.
AU - Dennis, Courtney
AU - Liang, Liming
AU - Corella, Dolores
AU - Fitó, Montserrat
AU - Razquin, Cristina
AU - Lapetra, José
AU - Estruch, Ramón
AU - Ros, Emilio
AU - Cofán, Montserrat
AU - Arós, Fernando
AU - Toledo, Estefania
AU - Serra-Majem, Lluis
AU - Sorlí, José V.
AU - Hu, Frank B.
AU - Martinez-Gonzalez, Miguel A.
AU - Salas-Salvado, Jordi
N1 - Publisher Copyright: © 2018 American Association for Clinical Chemistry.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1373/clinchem.2018.288720
DO - 10.1373/clinchem.2018.288720
M3 - Journal article
C2 - 29884676
AN - SCOPUS:85052685542
VL - 64
SP - 1211
EP - 1220
JO - Clinical Chemistry
JF - Clinical Chemistry
SN - 0009-9147
IS - 8
ER -
ID: 358092629