Dietary Glutamine and Glutamate in Relation to Cardiovascular Disease Incidence and Mortality in the United States Men and Women with Diabetes Mellitus

Zhangling Chen, Yang Hu, Frank B. Hu, Jo Ann E. Manson, Eric B. Rimm, Alessandro Doria, Qi Sun*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)



Evidence regarding the potential health effects of dietary amino acids glutamine and glutamate among individuals with type 2 diabetes (T2D) is limited. 


The aim was to examine dietary glutamine and glutamate in relation to subsequent risk of cardiovascular disease (CVD) and mortality among individuals with T2D.


We prospectively followed 15,040 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1980–2014 and Health Professionals Follow-Up Study: 1986–2018). Diet was repeatedly assessed using validated food frequency questionnaires every 2–4 y. Associations of energy-adjusted glutamine and glutamate intake, as well as their ratio, with CVD risk and mortality, were assessed using Cox proportional-hazards models with adjustments for demographics, dietary and lifestyle factors, and medical history. 


During 196,955 and 225,371 person-years of follow-up in participants with T2D, there were 2927 incident CVD cases and 4898 deaths, respectively. Higher intake of glutamine was associated with lower risk of CVD incidence, CVD mortality, and total mortality: comparing extreme quintiles, the hazard ratios (HRs) (95% confidence intervals [CIs]) were 0.88 (0.77, 0.99), 0.78 (0.65, 0.92), and 0.84 (0.76, 0.92), respectively (all P-trend < 0.05). In contrast, higher intake of glutamate was associated with a higher risk of CVD incidence, CVD mortality, and total mortality; the HRs were 1.30 (1.15, 1.46), 1.46 (1.24, 1.72), and 1.20 (1.09, 1.32), respectively (all P-trend < 0.05). Furthermore, comparing extreme quintiles, a higher dietary glutamine-to-glutamate ratio was associated with a lower risk of CVD incidence (0.84 [0.75, 0.95]), CVD mortality (0.66 [0.57, 0.77]), and total mortality (0.82 [0.75, 0.90]). In addition, compared with participants with stable or decreased consumption of glutamine-to-glutamate ratio from prediabetes to postdiabetes diagnosis, those who increased the ratio had a 17% (5%, 27%) lower CVD mortality. 


In adults with T2D, dietary glutamine was associated with a lower risk of CVD incidence and mortality, whereas the opposite was observed for glutamate intake.

Original languageEnglish
Pages (from-to)3247-3258
Number of pages12
JournalJournal of Nutrition
Issue number11
Early online date3 Sept 2023
Publication statusPublished - Nov 2023

Bibliographical note

Funding Information:
We would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, and Wyoming.

Funding Information:
The NHS and HPFS studies and the current analysis are supported by National Institutes of Health grants UM1 CA186107, P01 CA87969, R01 CA49449, R01 HL034594, U01 HL145386, R01 HL088521, U01 CA176726, R01 CA67262, U01 CA167552, R01 HL035464, R01 HL060712, R01 HL132254, and R01 DK120870. The funding sources did not play a role in the design or conduct of the study; collection, management, analyses or interpretation of the data; or preparation, review, or approval of the manuscript.

Publisher Copyright:
© 2023 American Society for Nutrition


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