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

被引：72

作者：

Liu, Xiaoran ^{[1
]}

Zheng, Yan ^{[1
,2
,3
]}

Guasch-Ferre, Marta ^{[1
]}

Ruiz-Canela, Miguel ^{[4
,5
]}

Toledo, Estefania ^{[4
,5
]}

Clish, Clary ^{[6
]}

Liang, Liming ^{[7
,8
]}

Razquin, Cristina ^{[4
,5
]}

Corella, Dolores ^{[5
,9
]}

Estruch, Ramon ^{[5
,10
]}

Fito, Montserrat ^{[5
,11
]}

Gomez-Gracia, Enrique ^{[5
,12
]}

Aros, Fernando ^{[5
,13
]}

Ros, Emilio ^{[5
,14
]}

Lapetra, Jose ^{[5
,15
]}

Fiol, Miquel ^{[5
,16
,17
]}

Serra-Majem, Lluis ^{[5
,18
]}

Papandreou, Christopher ^{[5
,19
]}

Martinez-Gonzalez, Miguel A. ^{[1
,4
,5
]}

Hu, Frank B. ^{[1
,20
]}

Salas-Salvado, Jordi ^{[5
,19
]}

机构：

[1] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA

[2] Fudan Univ, Human Phenome Inst, State Key Lab Genet Engn, Shanghai, Peoples R China

[3] Fudan Univ, Sch Life Sci, Shanghai, Peoples R China

[4] Univ Navarra, Dept Prevent Med & Publ Hlth, IDISNA Inst Invest Sanitaria Navarra, Pamplona, Spain

[5] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CIBERObn, Madrid, Spain

[6] Broad Inst MIT & Harvard Univ, Cambridge, MA USA

[7] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[8] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

[9] Univ Valencia, Dept Prevent Med, Valencia, Spain

[10] Univ Barcelona, Hosp Clin, IDI BAPS, Dept Internal Med,Dept Endocrinol & Nutr, Barcelona, Spain

[11] Hosp del Mar IMIM, Inst Recerca, Cardiovasc & Nutr Res Grp, Regicor Study Grp, Barcelona, Spain

[12] Univ Malaga, Dept Prevent Med, Malaga, Spain

[13] Univ Hosp Alava, Dept Cardiol, Vitoria, Spain

[14] Univ Barcelona, Hosp Clin, IDIBAPS, Lipid Clin,Endocrinol & Nutr Serv, Barcelona, Spain

[15] Primary Care Div Sevilla, Dept Family Med, Res Unit, Seville, Spain

[16] Univ Balearic Isl, IUNICS, Inst Hlth Sci, Palma De Mallorca, Spain

[17] Hosp Son Espases, Palma De Mallorca, Spain

[18] Univ Las Palmas Gran Canaria, Res Inst Biomed & Hlth Sci, Las Palmas Gran Canaria, Spain

[19] Rovira & Virgili Univ, Inst Invest Sanitaria Pere Virgili, Fac Med & Hlth Sci, Human Nutr Unit, Reus, Spain

[20] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

来源：

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES | 2019年 / 29卷 / 10期

基金：

美国国家卫生研究院;

关键词：

Glutamine; Glutamate; Type-2; diabetes; Mediterranean diet; GLUCAGON-LIKE PEPTIDE-1; RISK; METABOLISM; OBESE;

D O I：

10.1016/j.numecd.2019.06.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (C) 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.

引用

页码：1040 / 1049

页数：10

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