Guanine and pregnenolone sulfate are associated with incident type 2 diabetes in two independent populations
Barranco-Altirriba, Maria (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Granado-Casas, Minerva (Institut Universitari d'Investigació en Atenció Primària Jordi Gol)
Yanes, Oscar (Universitat Rovira i Virgili)
Capellades, Jordi (Instituto de Salud Carlos III)
Junza, Alexandra (Universitat Rovira i Virgili)
Franch-Nadal, Josep (Institut Universitari d'Investigació en Atenció Primària Jordi Gol)
Vendrell, Joan (Universitat Rovira i Virgili)
Llauradó, Gemma (Hospital del Mar (Barcelona, Catalunya))
Valdés, Sergio (Hospital Regional Universitario de Málaga)
García-Escobar, Eva (Hospital Regional Universitario de Málaga)
Bermúdez-López, Marcelino (Institut de Recerca Biomédica IRBLleida)
Valdivielso, José Manuel (Institut de Recerca Biomédica IRBLleida)
López-Lifante, Víctor-Miguel (Institut Català de la Salut)
Herrero Alonso, Cecilia (Institut Universitari d'Investigació en Atenció Primària Jordi Gol)
Falguera, Mireia (Institut Català de la Salut)
Vilanova, Maria Belén (Consorci Sanitari de l'Anoia)
Arteaga, Ingrid (Institut Universitari d'Investigació en Atenció Primària Jordi Gol)
Torán Monserrat, Pere (Institut Universitari d'Investigació en Atenció Primària Jordi Gol)
Perera Lluna, Alexandre (Institut de Recerca Sant Joan de Déu)
Castelblanco, Esmeralda (Washington University School of Medicine)
Mauricio, Didac (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona. Departament de medicina

Date:	2025
Abstract:	Type 2 diabetes (T2D) is increasing its burden worldwide; therefore, research focused on its prediction and prevention is essential. We performed an untargeted metabolomics analysis using ultra high-performance liquid chromatography-mass spectrometry to discover metabolic biomarkers and biological pathways associated with incident T2D with a nested case-control design, followed by validation with targeted metabolomics in an independent cohort. In the discovery phase, plasma samples from 352 subjects (209 controls and 143 incident cases) were analyzed, collected with a mean (standard deviation) of 7. 40 (0. 76) years before they acquired the condition. Using this discovery phase cohort, six metabolites were identified using standards and were subsequently quantified in an independent validation phase cohort of 2,044 subjects (167 incident cases). Additionally, pathway enrichment was conducted in the discovery cohort. Guanine, ecgonine, adenine, pregnenolone sulfate, phenyl sulfate, and citrulline were significantly associated with incident T2D in at least one of the analyses performed in the discovery phase. Among these, guanine, pregnenolone sulfate, and citrulline maintained their significant associations with incident T2D in the validation cohort. Additionally, several pathways were significantly altered, with nucleotide metabolism and ABC transporter pathways among the most consistently affected. We identified significant associations of guanine, pregnenolone sulfate, and citrulline with incident T2D.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Incident type 2 diabetes ; Liquid chromatography ; Mass spectrometry ; Untargeted metabolomics ; Targeted metabolomics
Published in:	Frontiers in endocrinology, Vol. 16 (December 2025) , art. 1706886, ISSN 1664-2392

DOI: 10.3389/fendo.2025.1706886
PMID: 41416067

12 p, 3.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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