期刊
CLINICAL CHEMISTRY
卷 64, 期 8, 页码 1211-1220出版社
OXFORD UNIV PRESS INC
DOI: 10.1373/clinchem.2018.288720
关键词
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资金
- National Institutes of Health [R01DK102896, F31DK114938]
- Spanish Ministry of Health (Instituto de Salud Carlos III)
- Spanish Ministry of Health (PREDIMED Network) [RD 06/0045]
- Spanish Ministry of Health [RTIC-G03/140]
- Ministerio de Economia y Competitividad-Fondo Europeo de Desarrollo Regional [CNIC-06/2007, CIBER 06/03, PI06-1326, PI07-0954, PI11/02505, SAF2009-12304, AGL2010-22319-C03-03]
- Generalitat Valenciana [ACOMP2010-181, AP111/10, AP-042/11, ACOM2011/145, ACOMP/2012/190, ACOMP/2013/159, ACOMP/213/165]
- Autonomous Government of Catalonia [SLT002/0016/00428]
- Private Foundation Daniel Bravo (Spain)
- International Nut and Dried Fruit Foundation
- California Walnut Commission
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [F31DK114938, R01DK102896] Funding Source: NIH RePORTER
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 Prevencion con Dieta Mediterranea (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. (C) 2018 American Association for Clinical Chemistry
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