RT Journal Article
T1 Glycolysis/gluconeogenesis- and tricarboxylic acid cycle-related metabolites, Mediterranean diet, and type 2 diabetes.
A1 Guasch-Ferré, Marta
A1 Santos, José L
A1 Martínez-González, Miguel A
A1 Clish, Clary B
A1 Razquin, Cristina
A1 Wang, Dong
A1 Liang, Liming
A1 Li, Jun
A1 Dennis, Courtney
A1 Corella, Dolores
A1 Muñoz-Bravo, Carlos
A1 Romaguera, Dora
A1 Estruch, Ramón
A1 Santos-Lozano, José Manuel
A1 Castañer, Olga
A1 Alonso-Gómez, Angel
A1 Serra-Majem, Luis
A1 Ros, Emilio
A1 Canudas, Sílvia
A1 Asensio, Eva M
A1 Fitó, Montserrat
A1 Pierce, Kerry
A1 Martínez, J Alfredo
A1 Salas-Salvadó, Jordi
A1 Toledo, Estefanía
A1 Hu, Frank B
A1 Ruiz-Canela, Miguel
K1 glycolysis metabolites
K1 insulin resistance
K1 metabolomics
K1 tricarboxylic acid cycle metabolites
K1 type 2 diabetes
AB 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. 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. 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-one-out cross-validation approach. Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D 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. We identified a panel of glycolysis/gluconeogenesis-related 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.This trial was registered at controlled-trials.com as ISRCTN35739639.
YR 2020
FD 2020
LK https://hdl.handle.net/10668/24802
UL https://hdl.handle.net/10668/24802
LA en
DS RISalud
RD Apr 6, 2025