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

Background: Evidence regarding the potential health effects of dietary amino acids glutamine and glutamate among individuals with type 2 diabetes (T2D) is limited.Objectives: The aim was to examine dietary glutamine and glutamate in relation to subsequent risk of cardiovascular disease (CVD) and mortality among individuals with T2D.Methods: 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.Results: 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. Conclusions: 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.