Author, as appears in the article.: Guasch-Ferre, Marta; Santos, Jose L; Martinez-Gonzalez, Miguel A; Clish, Clary B; Razquin, Cristina; Wang, Dong; Liang, Liming; Li, Jun; Dennis, Courtney; Corella, Dolores; Munoz-Bravo, Carlos; Romaguera, Dora; Estruch, Ramon; Manuel Santos-Lozano, Jose; Castaner, Olga; Alonso-Gomez, Angel; Serra-Majem, Luis; Ros, Emilio; Canudas, Silvia; Asensio, Eva M; Fito, Montserrat; Pierce, Kerry; Alfredo Martinez, J; Salas-Salvado, Jordi; Toledo, Estefania; Hu, Frank B; Ruiz-Canela, Miguel
Department: Bioquímica i Biotecnologia
URV's Author/s: Salas Salvadó, Jorge
Keywords: Type 2 diabetes Tricarboxylic acid cycle metabolites Tca cycle Skeletal-muscle Profiles Plasma lactate Metabolomics Insulin-resistance Insulin resistance Glycolysis metabolites Glucose Design Atherosclerosis risk
Abstract: Background: Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear.
Objectives: We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions.
Methods: We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil. MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC-tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-oneout cross-validation approach.
Results: Baseline circulating concentrations of hexose monophosphate. pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T21) risk (17-44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1-y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons.
Conclusions: We identified a panel of glycolysis/gluconeogenesisrelated metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites.
Thematic Areas: Serviço social Saúde coletiva Odontología Nutrition and dietetics Nutrition & dietetics Nutrição Medicine (miscellaneous) Medicina iii Medicina ii Medicina i General medicine Enfermagem Educação física Ciências biológicas ii Ciência de alimentos Biotecnología
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 00029165
Author's mail: jordi.salas@urv.cat
Author identifier: 0000-0003-2700-7459
Record's date: 2024-04-27
Papper version: info:eu-repo/semantics/acceptedVersion
Papper original source: American Journal Of Clinical Nutrition. 111 (4): 835-844
APA: Guasch-Ferre, Marta; Santos, Jose L; Martinez-Gonzalez, Miguel A; Clish, Clary B; Razquin, Cristina; Wang, Dong; Liang, Liming; Li, Jun; Dennis, Court (2020). Glycolysis/gluconeogenesis- and tricarboxylic acid cycle-related metabolites, Mediterranean diet, and type 2 diabetes. American Journal Of Clinical Nutrition, 111(4), 835-844. DOI: 10.1093/ajcn/nqaa016
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Entity: Universitat Rovira i Virgili
Journal publication year: 2020
Publication Type: Journal Publications
Repositori URV