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Nutr Metab Cardiovasc Dis. 2019 Oct;29(10):1040-1049. doi: 10.1016/j.numecd.2019.06.005. Epub 2019 Jun 20.

High plasma glutamate and low glutamine-to-glutamate ratio are associated with type 2 diabetes: Case-cohort study within the PREDIMED trial.

Author information

1
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
2
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; State Key Laboratory of Genetic Engineering, Human Phenome Institute and School of Life Sciences, Fudan University, Shanghai, China.
3
University of Navarra, Department of Preventive Medicine and Public Health, IDISNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.
4
Broad Institute of MIT and Harvard University, Cambridge, MA, USA.
5
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
6
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Department of Preventive Medicine, University of Valencia, Valencia, Spain.
7
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Department of Internal Medicine, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
8
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Cardiovascular and Nutrition Research Group (Regicor Study Group), Institut de Recerca-Hospital del Mar (IMIM), Barcelona, Spain.
9
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Department of Preventive Medicine, University of Málaga, Málaga, Spain.
10
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Department of Cardiology, University Hospital of Alava, Vitoria, Spain.
11
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Lipid Clinic, Endocrinology and Nutrition Service, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
12
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Department of Family Medicine, Research Unit, Primary Care Division of Sevilla, Sevilla, Spain.
13
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Institute of Health Sciences IUNICS, University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain.
14
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain.
15
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain.
16
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; University of Navarra, Department of Preventive Medicine and Public Health, IDISNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.
17
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
18
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain. Electronic address: jordi.salas@urv.cat.

Abstract

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.

KEYWORDS:

EVOO; Extra virgin olive oil; Glutamate; Glutamine; MedDiet: mediterranean diet; Mediterranean diet; Type-2 diabetes

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