Mediation of endothelial activation and stress index in the association between vitamin B6 turnover rate and diabetic retinopathy: an analysis of the National Health and Nutrition Examination Survey

Abstract

Aim: This study aimed to explore the association between the ratio of 4-pyridoxine (4-PA) to pyridoxal 5'-phosphate (PLP) (4-PA/PLP) and diabetic retinopathy (DR) and further assess the mediating effect of Endothelial Activation and Stress Index (EASIX) on the association between 4-PA/PLP and DR.

Methods: In this cross-sectional study, 1,698 patients with diabetes from the National Health and Nutrition Examination Survey were included. According to the median, 4-PA/PLP was categorized into a high-level group (≥0.89) and a low-level group (<0.89). As the EASIX had a skewed distribution, it was log-transformed before analysis. Weighted logistic regression models were used to investigate the association of 4-PA/PLP with EASIX and DR and the mediating effect of EASIX on the association between 4-PA/PLP and DR. The distribution-of-product method was adopted to assess the mediating effect. Subgroup analysis was performed based on the age and duration of diabetes.

Results: A total of 362 diabetic patients were classified as having DR. After adjusting for all covariates, a higher level of 4-PA/PLP was associated with an increased level of log EASIX [odds ratio (OR) = 1.56, 95% confidence interval (CI): 1.06-2.30]. A higher ratio of 4-PA/PLP was associated with increased odds of DR compared to the reference group with lower levels of 4-PA/PLP (OR = 1.94, 95%CI: 1.40-2.67). In addition, we found that log EASIX may play a mediating role in the 4-PA/PLP and DR, with a 95% CI of distribution of product of 0.31 (95% CI: 0.02-0.67). The proportion of mediation was 69.06%. The mediating effect of log EASIX was also observed in individuals with diabetes who were aged≥60 years (proportion of mediation: 50.63%) or had a duration of diabetes ≥10 years (proportion of mediation: 71.83%).

Conclusion: This study found a positive association between high levels of 4-PA/PLP and an increased risk of DR, with the relationship being partially mediated by log EASIX.

Keywords: 4-PA/PLP; DR; EASIX; distribution-of-product method; mediating effect.

Figure 1

Flowchart of the participants screening. NHANES, National Health and Nutrition Examination Survey; 4-PA, 4-pyridoxine; PLP, pyridoxal 5′-phosphate; LDH, lactate dehydrogenase; DR, diabetic retinopathy.

Figure 2

Path diagram of the mediation analysis models. Path a: estimated coefficient for the regression with 4-PA/PLP predicting log EASIX; Path b: estimated coefficient for the regression with log EASIX predicting DR; Path c = total effects for the regression with 4-PA/PLP predicting DR; Path c’ = direct effects for the regression with 4-PA/PLP predicting DR independent of log EASIX. 4-PA/PLP: the ratio of 4-pyridoxine (4-PA) to pyridoxal 5′-phosphate (PLP); EASIX: Endothelial Activation and Stress Index; DR: diabetic retinopathy.