Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy

Introduction: Diabetic patients with a long disease duration usually accompanied complication such as diabetic retinopathy, but in some patients had no complication. Objectives: We analyzed differences in plasma metabolites according to the presence or absence of diabetic retinopathy (DR) in type 2 diabetic (T2D) patients with disease duration ≥ 15 years. Methods: A cohort of 183 T2D patients was established. Their biospecimens and clinical information were collected in accordance with the guidelines of the National Biobank of Korea, and the Korean Diabetes Association. DR phenotypes of the subjects were verified by ophthalmologic specialists. Plasma metabolites were analyzed using gas chromatography time-of-flight mass spectrometry and ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry. And these results were analyzed using multivariate statistics. Results: For metabolomic study, propensity score matched case and control subjects were chosen. Mean age of the subjects was 66.4 years and mean T2D duration was 22.2 years. Metabolomic identification revealed various carbohydrates, amino acids, and organic compounds that distinguished between age- and sex-matched non-diabetic controls and T2D subjects. Among these, glutamine and glutamic acid were suggested as the most distinctive metabolites for the presence of DR. Receiver operating characteristics curves showed an excellent diagnostic value of combined (AUC = 0.739) and the ratio (AUC = 0.742) of glutamine and glutamic acid for DR. And these results were consistent in validation analyses. Conclusion: Our results imply that plasma glutamine, glutamic acid, and their ratio may be valuable as novel biomarkers for anticipating DR in T2D subjects.