Glycolysis/gluconeogenesis- and tricarboxylic acid cycle-related metabolites, Mediterranean diet, and type 2 diabetes.

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-one-out cross-validation approach.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Marta Guasch-Ferré, José L Santos, Miguel A Martínez-González, Clary B Clish, Cristina Razquin, Dong Wang, Liming Liang, Jun Li, Courtney Dennis, Dolores Corella, Carlos Muñoz-Bravo, Dora Romaguera, Ramón Estruch, José Manuel Santos-Lozano, Olga Castañer, Angel Alonso-Gómez, Luis Serra-Majem, Emilio Ros, Sílvia Canudas, Eva M Asensio, Montserrat Fitó, Kerry Pierce, J Alfredo Martínez, Jordi Salas-Salvadó, Estefanía Toledo, Frank B Hu, Miguel Ruiz-Canela
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 111 Issue 4 Pg. 835-844 (04 01 2020) ISSN: 1938-3207 [Electronic] United States
• PMID: 32060497 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © The Author(s) 2020.

Topics

• Aged
• Aged, 80 and over
• Case-Control Studies
• Citric Acid Cycle
• Cohort Studies
• Diabetes Mellitus, Type 2 (diet therapy, metabolism, physiopathology)
• Diet, Mediterranean
• Female
• Gluconeogenesis
• Glycolysis
• Humans
• Male
• Middle Aged