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


  • 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.


  • Papandreou, Christopher
  • Li, Jun
  • Liang, Liming
  • Bulló, Mònica
  • Zheng, Yan
  • Ruiz-Canela, Miguel
  • Yu, Edward
  • Guasch-Ferré, Marta
  • Razquin, Cristina
  • Clish, Clary
  • Corella, Dolores
  • Estruch, Ramon
  • Ros, Emilio
  • Fitó, Montserrat
  • Arós, Fernando
  • Serra-Majem, Lluís
  • Rosique, Nuria
  • Martinez-Gonzalez, Miguel A
  • Hu, Frank B
  • Salas-Salvadó, Jordi

publication date

  • 2019