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

Scientific Reports
Christopher PapandreouJordi Salas-Salvadó

Abstract

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.

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Citations

Apr 17, 2020·Diabetes Care·Jagadish VangipurapuMarkku Laakso
Sep 14, 2019·Archives of Physiology and Biochemistry·Yogaraje Gowda C VaradaiahKashinath R Thirumalarao
Jun 11, 2020·Current Diabetes Reports·Giulio R Romeo, Meenu Jain
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Hugo Varela-RodríguezAlfredo Cruz-Ramirez
Feb 23, 2021·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Zhensheng ZhangXiao Xu
May 1, 2021·Current Opinion in Clinical Nutrition and Metabolic Care·Kendra L Nelson, Venkata Saroja Voruganti
Jul 31, 2021·Journal of the American College of Cardiology·Matthew NayorRavi V Shah
Aug 27, 2021·Metabolites·Soon Yeon JeongSooah Kim

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Methods Mentioned

BETA
deamination

Clinical Trials Mentioned

ISRCTN35739639

Software Mentioned

TraceFinder
Progenesis QI
Stata

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