Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism

Autores: Papandreu, C.; Li, J.; Bullo, M. (Autor de correspondencia); Zheng, Y.; Ruiz-Canela, Miguel; Yu, E.; Guasch-Ferre, M.; Razquin Burillo, Cristina; Clish, C.; Corella, D.; Estruch, R.; Ros, E.; Fito, M.; Aros, F.; Serra-Majem, L.; Rosique, N. ; Martínez González, Miguel Ángel; Hu, F. B.; Salas-Salvado, J. (Autor de correspondencia)
Título de la revista: SCIENTIFIC REPORTS
ISSN: 2045-2322
Volumen: 9
Páginas: 2892
Fecha de publicación: 2019
Lugar: WOS
Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated.