Abstract P418: Dietary Glutamine and Glutamate in Relation to Cardiovascular Disease and Mortality in Adults With Type 2 Diabetes

Background: The potential health effects of dietary glutamine and glutamate have been studied in healthy populations, but evidence among individuals with type 2 diabetes (T2D) who have altered macronutrient metabolism and elevated cardiovascular disease (CVD) risk is limited. Objectives: We aimed to examine dietary glutamine and glutamate in relation to subsequent risk of CVD, including coronary heart disease and stroke, and all-cause and cause-specific 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, Health Professionals Follow-Up Study: 1986-2018). Diet was repeatedly assessed using validated food frequency questionnaires every 2-4 years since baseline. 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 225,371person-years of follow-up in participants with T2D, there were 2,927 incident CVD cases and 4,898 deaths, respectively. Higher intake of glutamine was associated with lower risk of incident CVD, total mortality and CVD mortality: comparing extreme quintiles, the HRs (95%CIs) were 0.88 (0.77, 0.99), 0.85 (0.77, 0.94), and 0.82 (0.69, 0.98), respectively (all P trend <0.05). In contrast, higher intake of glutamate was associated with higher risk of incident CVD, total mortality, and CVD mortality; the HRs were 1.30 (1.15, 1.46), 1.19 (1.08, 1.31), and 1.42 (1.21, 1.67), respectively (all P trend <0.05). Furthermore, comparing extreme quintiles, higher dietary glutamine-to-glutamate ratio was associated with lower risk of CVD incidence (0.84 (0.75, 0.95)), total mortality (0.83 (0.76, 0.91)), and CVD mortality (0.69 (0.59, 0.80)). In addition, compared with participants without increment in glutamine-to-glutamate ratio from pre- to post-diabetes diagnosis, those who increased the ratio had a 15% (3%, 25%) lower CVD mortality. Conclusions: In patients with T2D, dietary glutamine and glutamate demonstrated divergent associations with CVD incidence and mortality, and higher dietary glutamine-to-glutamate ratio was significantly associated with lower CVD incidence and mortality. These data suggest a potential critical role of these two amino acids in the etiology of cardiometabolic diseases and early deaths also among adults with T2D.