TY - JOUR

T1 - High plasma glutamate and low glutamine-to-glutamate ratio are associated with type 2 diabetes

T2 - Case-cohort study within the PREDIMED trial

AU - Liu, Xiaoran

AU - Zheng, Yan

AU - Guasch-Ferré, Marta

AU - Ruiz-Canela, Miguel

AU - Toledo, Estefanía

AU - Clish, Clary

AU - Liang, Liming

AU - Razquin, Cristina

AU - Corella, Dolores

AU - Estruch, Ramón

AU - Fito, Montserrat

AU - Gómez-Gracia, Enrique

AU - Arós, Fernando

AU - Ros, Emilio

AU - Lapetra, José

AU - Fiol, Miquel

AU - Serra-Majem, Lluis

AU - Papandreou, Christopher

AU - Martínez-González, Miguel A

AU - Hu, Frank B

AU - Salas-Salvadó, Jordi

N1 - Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

PY - 2019

Y1 - 2019

N2 - BACKGROUND AND AIMS: Glutamate, glutamine are involved in energy metabolism, and have been related to cardiometabolic disorders. However, their roles in the development of type-2 diabetes (T2D) remain unclear. The aim of this study was to examine the effects of Mediterranean diet on associations between glutamine, glutamate, glutamine-to-glutamate ratio, and risk of new-onset T2D in a Spanish population at high risk for cardiovascular disease (CVD).METHODS AND RESULTS: The present study was built within the PREDIMED trial using a case-cohort design including 892 participants with 251 incident T2D cases and 641 non-cases. Participants (mean age 66.3 years; female 62.8%) were non diabetic and at high risk for CVD at baseline. Plasma levels of glutamine and glutamate were measured at baseline and after 1-year of intervention. Higher glutamate levels at baseline were associated with increased risk of T2D with a hazard ratio (HR) of 2.78 (95% CI, 1.43-5.41, P for trend = 0.0002). In contrast, baseline levels of glutamine (HR: 0.64, 95% CI, 0.36-1.12; P for trend = 0.04) and glutamine-to-glutamate ratio (HR: 0.31, 95% CI, 0.16-0.57; P for trend = 0.0001) were inversely associated with T2D risk when comparing extreme quartiles. The two Mediterranean diets (MedDiet + EVOO and MedDiet + mixed nuts) did not alter levels of glutamine and glutamate after intervention for 1 year. However, MedDiet mitigated the positive association between higher baseline plasma glutamate and T2D risk (P for interaction = 0.01).CONCLUSION: Higher levels of glutamate and lower levels of glutamine were associated with increased risk of T2D in a Spanish population at high risk for CVD. Mediterranean diet might mitigate the association between the imbalance of glutamine and glutamate and T2D risk. This trial is registered at http://www.controlled-trials.com, ISRCTN35739639.

AB - BACKGROUND AND AIMS: Glutamate, glutamine are involved in energy metabolism, and have been related to cardiometabolic disorders. However, their roles in the development of type-2 diabetes (T2D) remain unclear. The aim of this study was to examine the effects of Mediterranean diet on associations between glutamine, glutamate, glutamine-to-glutamate ratio, and risk of new-onset T2D in a Spanish population at high risk for cardiovascular disease (CVD).METHODS AND RESULTS: The present study was built within the PREDIMED trial using a case-cohort design including 892 participants with 251 incident T2D cases and 641 non-cases. Participants (mean age 66.3 years; female 62.8%) were non diabetic and at high risk for CVD at baseline. Plasma levels of glutamine and glutamate were measured at baseline and after 1-year of intervention. Higher glutamate levels at baseline were associated with increased risk of T2D with a hazard ratio (HR) of 2.78 (95% CI, 1.43-5.41, P for trend = 0.0002). In contrast, baseline levels of glutamine (HR: 0.64, 95% CI, 0.36-1.12; P for trend = 0.04) and glutamine-to-glutamate ratio (HR: 0.31, 95% CI, 0.16-0.57; P for trend = 0.0001) were inversely associated with T2D risk when comparing extreme quartiles. The two Mediterranean diets (MedDiet + EVOO and MedDiet + mixed nuts) did not alter levels of glutamine and glutamate after intervention for 1 year. However, MedDiet mitigated the positive association between higher baseline plasma glutamate and T2D risk (P for interaction = 0.01).CONCLUSION: Higher levels of glutamate and lower levels of glutamine were associated with increased risk of T2D in a Spanish population at high risk for CVD. Mediterranean diet might mitigate the association between the imbalance of glutamine and glutamate and T2D risk. This trial is registered at http://www.controlled-trials.com, ISRCTN35739639.

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers/blood

KW - Cardiovascular Diseases/blood

KW - Case-Control Studies

KW - Diabetes Mellitus, Type 2/blood

KW - Diet, Healthy

KW - Diet, Mediterranean

KW - Female

KW - Glutamic Acid/blood

KW - Glutamine/blood

KW - Humans

KW - Incidence

KW - Male

KW - Middle Aged

KW - Primary Prevention/methods

KW - Randomized Controlled Trials as Topic

KW - Spain/epidemiology

KW - Time Factors

KW - Treatment Outcome

U2 - 10.1016/j.numecd.2019.06.005

DO - 10.1016/j.numecd.2019.06.005

M3 - Journal article

C2 - 31377179

VL - 29

SP - 1040

EP - 1049

JO - Nutrition, Metabolism & Cardiovascular Diseases

JF - Nutrition, Metabolism & Cardiovascular Diseases

SN - 0939-4753

IS - 10

ER -