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.

Details

Title
Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism
Author
Papandreou, Christopher 1 ; Li, Jun 2 ; Liang Liming 3   VIAFID ORCID Logo  ; Bulló Mònica 1 ; Zheng, Yan 2 ; Ruiz-Canela, Miguel 4   VIAFID ORCID Logo  ; Yu, Edward 2 ; Guasch-Ferré, Marta 5 ; Razquin Cristina 4 ; Clary, Clish 6   VIAFID ORCID Logo  ; Corella Dolores 7   VIAFID ORCID Logo  ; Estruch Ramon 8 ; Ros, Emilio 9 ; Fitó Montserrat 10 ; Arós Fernando 11 ; Serra-Majem Lluís 12 ; Rosique Nuria 1 ; Martínez-González, Miguel A 13 ; Hu, Frank B 14 ; Salas-Salvadó Jordi 1   VIAFID ORCID Logo 

1  Institut d’Investigació Sanitària Pere Virgili, Rovira i Virgili University, Human Nutrition Unit, Faculty of Medicine and Health Sciences, Reus, Spain (GRID:grid.410367.7) (ISNI:0000 0001 2284 9230); Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427) 
2  Harvard T.H. Chan School of Public Health, Department of Nutrition, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
3  Harvard T.H. Chan School of Public Health, Departments of Epidemiology and Statistics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
4  Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); University of Navarra, Department of Preventive Medicine and Public Health, Pamplona, Spain (GRID:grid.5924.a) (ISNI:0000000419370271) 
5  Institut d’Investigació Sanitària Pere Virgili, Rovira i Virgili University, Human Nutrition Unit, Faculty of Medicine and Health Sciences, Reus, Spain (GRID:grid.410367.7) (ISNI:0000 0001 2284 9230); Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Harvard T.H. Chan School of Public Health, Department of Nutrition, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
6  Broad Institute of MIT and Harvard University, Cambridge, USA (GRID:grid.66859.34) 
7  Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); University of Valencia, Department of Preventive Medicine, Valencia, Spain (GRID:grid.5338.d) (ISNI:0000 0001 2173 938X) 
8  Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Hospital Clinic, University of Barcelona, Department of Internal Medicine, Department of Endocrinology and Nutrition Institut d’Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Barcelona, Spain (GRID:grid.410458.c) (ISNI:0000 0000 9635 9413) 
9  Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); University of Barcelona, Lipid Clinic, Department of Endocrinology and Nutrition Institut d’Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247) 
10  Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Institut de Recerca Hospital del Mar, Cardiovascular and Nutrition Research Group, Barcelona, Spain (GRID:grid.411142.3) (ISNI:0000 0004 1767 8811) 
11  Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); University Hospital of Alava, Department of Cardiology, Vitoria, Spain (GRID:grid.413448.e) 
12  Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); University of Las Palmas de Gran Canaria, Department of Clinical Sciences, Las Palmas, Spain (GRID:grid.4521.2) (ISNI:0000 0004 1769 9380) 
13  Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); Harvard T.H. Chan School of Public Health, Department of Nutrition, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); University of Navarra, Department of Preventive Medicine and Public Health, Pamplona, Spain (GRID:grid.5924.a) (ISNI:0000000419370271) 
14  Harvard T.H. Chan School of Public Health, Department of Nutrition, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard T.H. Chan School of Public Health, Departments of Epidemiology and Statistics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Brigham and Women’s Hospital and Harvard Medical School, Channing Division for Network Medicine, Department of Medicine, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-39441-6
ProQuest document ID
2186773036
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.