Guanine and pregnenolone sulfate are associated with incident type 2 diabetes in two independent populations
Por:
Barranco-Altirriba, M, Granado-Casas, M, Yanes, O, Capellades, J, Junza, A, Franch-Nadal, J, Vendrell, J, Llaurado, G, Valdés, S, García-Escobar, E, Bermúdez-Lopez, M, Valdivielso, JM, Lopez-Lifante, VM, Herrero-Alonso, C, Falguera, M, Vilanova, MB, Arteaga, I, Torán-Monserrat, P, Perera-Lluna, A, Castelblanco, E, Mauricio, D
Publicada:
3 dic 2025
Resumen:
Background Type 2 diabetes (T2D) is increasing its burden worldwide; therefore, research focused on its prediction and prevention is essential.Methods 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.Results 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.Conclusion We identified significant associations of guanine, pregnenolone sulfate, and citrulline with incident T2D.
Filiaciones:
Barranco-Altirriba, M:
Hosp Santa Creu I St Pau, Dept Endocrinol & Nutr, Barcelona, Spain
Univ Politecn Cataluna, Inst Recerca & Innovacio Salut IRIS, Bioinformat & Biomed Signals Lab B2SLab, Barcelona, Spain
Networking Biomed Res Ctr Subject Area Bioengn Bio, Madrid, Spain
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Barcelona, Spain
Granado-Casas, M:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Inst Univ Invest Atencio Primaria Jordi Gol, Res Support Unit, DAP Cat Grp, Barcelona, Spain
Univ Lleida, Fac Nursing & Physiotherapy, Dept Nursing & Physiotherapy, GESEC Grp, Lleida, Spain
Inst Biomed Res Lleida IRBLleida, Healthcare Res Grp GRECS, Lleida, Spain
Yanes, O:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Univ Rovira i Virgili, Inst Hlth Res Pere Virgili, Dept Elect Engn, Tarragona, Spain
Capellades, J:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Inst Hlth Res Pere Virgili IISPV, Tarragona, Spain
Junza, A:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Univ Rovira i Virgili, Sci & Tech Resources Serv, Tarragona, Spain
Franch-Nadal, J:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Inst Univ Invest Atencio Primaria Jordi Gol, Res Support Unit, DAP Cat Grp, Barcelona, Spain
Vendrell, J:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Univ Rovira i Virgili, Hosp Univ Tarragona Joan XXIII, Inst Invest Sanitaria Pere Virgili IISPV, Dept Endocrinol & Nutr,Res Unit, Tarragona, Spain
Llaurado, G:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Hosp del Mar, Med Res Inst IMIM, Dept Endocrinol & Nutr, Barcelona, Spain
Valdés, S:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Hosp Reg Univ Malaga, UGC Endocrinol & Nutr, IBIMA Plataforma BIONAND, Malaga, Spain
García-Escobar, E:
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Hosp Reg Univ Malaga, UGC Endocrinol & Nutr, IBIMA Plataforma BIONAND, Malaga, Spain
Bermúdez-Lopez, M:
Univ Lleida, Expt Med Dept, Lleida, Spain
Inst Recerca Biomed IRBLleida, Vasc & Renal Translat Res Grp, Lleida, Spain
Valdivielso, JM:
Inst Recerca Biomed IRBLleida, Vasc & Renal Translat Res Grp, Lleida, Spain
Lopez-Lifante, VM:
Univ Autonoma Barcelona, Fac Med, Bellaterra, Spain
Inst Univ Invest Atencio Primaria Jordi Gol IDIAP, Unitat Suport Recerca Metropolitana Nord, Mataro, Spain
Inst Catala Salut, Primary Healthcare Palau Solita & Plegamans, Gerencia Ambit Atencio Primaria Metropolitana Nord, Barcelona, Spain
Herrero-Alonso, C:
Inst Univ Invest Atencio Primaria Jordi Gol IDIAP, Unitat Suport Recerca Metropolitana Nord, Mataro, Spain
Falguera, M:
Inst Univ Invest Atencio Primaria Jordi Gol, Res Support Unit, DAP Cat Grp, Barcelona, Spain
Univ Lleida, Dr Pifarre Fdn IRB Lleida, Inst Biomed Res, Lleida, Spain
Inst Catala Salut, Primary Hlth Care Ctr Tarrega, Gerencia Atencio Primaria, Barcelona, Spain
Vilanova, MB:
Inst Univ Invest Atencio Primaria Jordi Gol, Res Support Unit, DAP Cat Grp, Barcelona, Spain
Consorci Sanitari Anoia, Primary Hlth Care Ctr Igualada Nord, Igualada, Spain
Arteaga, I:
Inst Univ Invest Atencio Primaria Jordi Gol IDIAP, Unitat Suport Recerca Metropolitana Nord, Mataro, Spain
Inst Catala Salut, Primary Healthcare Ctr Vall del Tenes, Gerencia Ambit Atencio Primaria Metropolitana Nord, Barcelona, Spain
Torán-Monserrat, P:
Inst Univ Invest Atencio Primaria Jordi Gol IDIAP, Unitat Suport Recerca Metropolitana Nord, Mataro, Spain
Univ Girona, Fac Med, Dept Med, Girona, Spain
Inst Univ Invest Atencio Primaria Jordi Gol IDIAPJ, Multidisciplinary Res Grp Hlth & Soc GREMSAS, Barcelona, Spain
Perera-Lluna, A:
Univ Politecn Cataluna, Inst Recerca & Innovacio Salut IRIS, Bioinformat & Biomed Signals Lab B2SLab, Barcelona, Spain
Networking Biomed Res Ctr Subject Area Bioengn Bio, Madrid, Spain
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Barcelona, Spain
Castelblanco, E:
Washington Univ, Sch Med, Dept Med, Div Endocrinol Metab & Lipid Res, St Louis, MO 63130 USA
Mauricio, D:
Hosp Santa Creu I St Pau, Dept Endocrinol & Nutr, Barcelona, Spain
Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red CIBER Diabet & Associated Me, Barcelona, Spain
Inst Invest Biomed St Pau IR St Pau, Barcelona, Spain
Cent Univ Catalonia, Univ Vic, Fac Med, Vic, Spain
Green Submitted, gold
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