Individual and joint effects of trehalose and glutamate on diabetic retinopathy: a propensity score-matched case–control study

Abstract

Although previous studies demonstrate that trehalose can help maintain glucose homeostasis in healthy humans, its role and joint effect with glutamate on diabetic retinopathy (DR) remain unclear. We aimed to comprehensively quantify the associations of trehalose and glutamate with DR. This study included 69 pairs of DR and matched type 2 diabetic (T2D) patients. Serum trehalose and glutamate were determined via ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry system. Covariates were collected by a standardized questionnaire, clinical examinations and laboratory assessments. Individual and joint association of trehalose and glutamate with DR were quantified by multiple conditional logistic regression models. The adjusted odds of DR averagely decreased by 86% [odds ratio (OR): 0.14; 95% confidence interval (CI): 0.06,0.33] with per interquartile range increase of trehalose. Comparing with the lowest quartile, adjusted OR (95% CI) were 0.20 (0.05,0.83), 0.14 (0.03,0.63) and 0.01 (<0.01,0.05) for participants in the 2nd, 3rd and 4th quartiles of trehalose, respectively. In addition, as compared to their counterparts, T2D patients with lower trehalose (<median) and higher glutamate (≥ median) had the highest odds of DR (OR: 36.81; 95% CI: 6.75, 200.61). Apparent super-multiplicative effect of trehalose and glutamate on DR was observed, whereas relative excess risk due to interaction (RERI) was not significant. The study suggests that trehalose is beneficial to inhibit the occurrence of DR and synergistically decreases the risk of DR with reduced glutamate. Our findings also provide new insights into the mechanisms of DR and further longitudinal studies are required to confirm these findings.

A new predictive model for the concurrent risk of diabetic retinopathy in type 2 diabetes patients and the effect of metformin on amino acids

“…Glu is associated with T2D, and studies have shown a 0.25 drop in Glu levels in diabetic subjects compared to non-diabetic controls (23). At the same time, studies have found that Glu is a risk factor for the incidence of DR (24), while another Korean study found that the intake of Glu did not affect the incidence of DR (25). We believe that in addition to the heterogeneity of the population, the metabolic interactions between amino acids should also be taken into account.…”