Methylmalonic acid and diabetic retinopathy: Joint associations and exploratory mediation by the albumin/neutrophil-to-lymphocyte ratio in a cross-sectional study
Jueyi Wu, Xinna Wu, Shunong Xie, Peng ZhuangObjective
To investigate the individual and joint associations of methylmalonic acid (MMA) and the albumin/neutrophil-to-lymphocyte ratio (ANLR) with self-reported diabetic retinopathy (DR), and to explore the potential involvement of ANLR in the association between MMA and DR.
Methods
Based on NHANES 2011-2014 cross-sectional data, weighted multiple logistic regression and restricted cubic splines (RCS) were performed to assess the associations of MMA and ANLR with DR. Joint analysis was used to evaluate the association of MMA combined with ANLR with DR, while exploratory mediation analysis was used to examine the statistical role of ANLR in the association between MMA and DR. Sensitivity analyses were performed by additionally adjusting for vitamin B12, glycated hemoglobin(HbA1c), and insulin or other glucose-lowering medication use.
Results
This study included 1,029 participants, of whom 205 (19.9%) reported physician-diagnosed DR. The analysis showed a positive association between log(MMA) and the odds of DR (OR=1.542, 95% CI: 1.004-2.369). A significant negative association was observed for log (ANLR) (OR=0.563, 95% CI: 0.355-0.894). RCS analysis suggested a positive association between log (MMA) and the odds of DR (P-nonlinear = 0.758) and a negative association between log (ANLR) and the odds of DR (P-nonlinear = 0.295). High MMA and low ANLR (MMA ≥250 nmol/L and log[ANLR] ≤ median) were associated with higher odds of DR (fully adjusted OR=2.233, 95% CI: 1.303–3.824). In the exploratory mediation analysis, ANLR accounted for 29.7% of the observed association between MMA and DR (P=0.028). The associations remained significant in sensitivity analyses with additional adjustment for serum vitamin B12, HbA1c, and insulin or other glucose-lowering medication use.
Conclusions
Elevated MMA was associated with greater odds of self-reported DR, while exploratory mediation analysis suggested that ANLR statistically accounted for part of this association. Joint consideration of MMA and ANLR may provide complementary information regarding self-reported DR.