Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial: A case–cohort study

Edward Yu; Christopher Papandreou; Miguel Ruiz-Canela; Marta Guasch-Ferre; Clary B. Clish; Courtney Dennis; Liming Liang; Dolores Corella; Montserrat Fitó; Cristina Razquin; José Lapetra; Ramón Estruch; Emilio Ros; Montserrat Cofán; Fernando Arós; Estefania Toledo; Lluis Serra-Majem; José V. Sorlí; Frank B. Hu; Miguel A. Martinez-Gonzalez; Jordi Salas-Salvado

doi:10.1373/clinchem.2018.288720

Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial: A case–cohort study

Edward Yu, Christopher Papandreou, Miguel Ruiz-Canela, Marta Guasch-Ferre, Clary B. Clish, Courtney Dennis, Liming Liang, Dolores Corella, Montserrat Fitó, Cristina Razquin, José Lapetra, Ramón Estruch, Emilio Ros, Montserrat Cofán, Fernando Arós, Estefania Toledo, Lluis Serra-Majem, José V. Sorlí, Frank B. Hu, Miguel A. Martinez-GonzalezJordi Salas-Salvado^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

84 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Clinical Chemistry
Vol/bind	64
Udgave nummer	8
Sider (fra-til)	1211-1220
Antal sider	10
ISSN	0009-9147
DOI	https://doi.org/10.1373/clinchem.2018.288720
Status	Udgivet - 2018
Udgivet eksternt	Ja

Bibliografisk note

Funding Information:
This study was funded by the National Institutes of Health (R01DK102896, F31DK114938), the Spanish Ministry of Health (Instituto de Salud Carlos III, The PREDIMED Network grant RD 06/0045, 2006 –2013, coordinated by M.A. Martínez-González; and a previous network grant RTIC-G03/140, 2003–2005, coordinated R. Estruch). Additional grants were received from the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (Projects CNIC-06/2007, CIBER 06/03, PI06-1326, PI07-0954, PI11/02505, SAF2009-12304 and AGL2010 –22319-C03-03) and by the Generalitat Valenciana (ACOMP2010-181, AP111/10, AP-042/11, ACOM2011/145, ACOMP/2012/190, ACOMP/2013/159 and ACOMP/213/165). C. Papandreou, postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS 2016 – 2020 Incorporació de Científics I Tecnòlegs, SLT002/0016/00428); M. Guasch-Ferré, fellowship granted by the Private Foundation Daniel Bravo (Spain); E. Ros, the California Walnut Commission; J. Salas-Salvadó, grants from the International Nut and Dried Fruit Foundation. The authors thank the contributions of Monica Bullo, Amy Diek, Dong Wang, and Yan Zheng, who provided invaluable assistance throughout the acquisition of data, analysis of data, and preparation of the manuscript.

Funding Information:
Employment or Leadership: None declared. Consultant or Advisory Role: J. Salas-Salvadó, the International Nut and Dried Fruit Foundation; E. Ros, Alexion, the California Walnut Commission. Stock Ownership: None declared. Honoraria: E. Ros, Alexion, California Walnut Commission, Merck, Sanofi. Research Funding: This study was funded by the National Institutes of Health (R01DK102896, F31DK114938), the Spanish Ministry of Health (Instituto de Salud Carlos III, The PREDIMED Network grant RD 06/0045, 2006–2013, coordinated by M.A. Martínez-González; and a previous network grant RTIC-G03/140, 2003–2005, coordinated R. Estruch). Additional grants were received from the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (Projects CNIC-06/2007, CIBER 06/03, PI06-1326, PI07-0954, PI11/02505, SAF2009-12304 and AGL2010–22319-C03-03) and by the Generalitat Valenciana (ACOMP2010-181, AP111/10, AP-042/11, ACOM2011/145, ACOMP/2012/190, ACOMP/2013/ 159 and ACOMP/213/165). C. Papandreou, postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS 2016– 2020 Incorporació de Científics I Tecnòlegs, SLT002/0016/00428); M. Guasch-Ferré, fellowship granted by the Private Foundation Daniel Bravo (Spain); E. Ros, the California Walnut Commission; J. Salas-Salvadó, grants from the International Nut and Dried Fruit Foundation. Expert Testimony: None declared. Patents: None declared.

Publisher Copyright:
© 2018 American Association for Clinical Chemistry.

Adgang til dokumentet

10.1373/clinchem.2018.288720

Citationsformater

Yu, E., Papandreou, C., Ruiz-Canela, M., Guasch-Ferre, 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., Sorlí, J. V., Hu, F. B., ... Salas-Salvado, J. (2018). Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial: A case–cohort study. Clinical Chemistry, 64(8), 1211-1220. https://doi.org/10.1373/clinchem.2018.288720

Yu, E, Papandreou, C, Ruiz-Canela, M, Guasch-Ferre, M, Clish, CB, 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, Sorlí, JV, Hu, FB, Martinez-Gonzalez, MA & Salas-Salvado, J 2018, 'Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial: A case–cohort study', Clinical Chemistry, bind 64, nr. 8, s. 1211-1220. https://doi.org/10.1373/clinchem.2018.288720

@article{a13ac93deba14627a483ae3614d47ab1,

title = "Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial: A case–cohort study",

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 Prevenci{\'o}n con Dieta Mediterr{\'a}nea (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.",

author = "Edward Yu and Christopher Papandreou and Miguel Ruiz-Canela and Marta Guasch-Ferre and Clish, {Clary B.} and Courtney Dennis and Liming Liang and Dolores Corella and Montserrat Fit{\'o} and Cristina Razquin and Jos{\'e} Lapetra and Ram{\'o}n Estruch and Emilio Ros and Montserrat Cof{\'a}n and Fernando Ar{\'o}s and Estefania Toledo and Lluis Serra-Majem and Sorl{\'i}, {Jos{\'e} V.} and Hu, {Frank B.} and Martinez-Gonzalez, {Miguel A.} and Jordi Salas-Salvado",

note = "Publisher Copyright: {\textcopyright} 2018 American Association for Clinical Chemistry.",

year = "2018",

doi = "10.1373/clinchem.2018.288720",

language = "English",

volume = "64",

pages = "1211--1220",

journal = "Clinical Chemistry",

issn = "0009-9147",

publisher = "American Association for Clinical Chemistry, Inc.",

number = "8",

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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

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

SN - 0009-9147

VL - 64

SP - 1211

EP - 1220

JO - Clinical Chemistry

JF - Clinical Chemistry

IS - 8

ER -