DME is a major cause of vision loss in individuals with T2DM. The metabolic and inflammatory components contributing to its development remain under investigation. This systematic review and meta-analysis evaluated the associations between HbA1c, white blood cell (WBC) counts, and the presence of DME in T2DM.

A total of 48 studies involving 207,536 individuals were included. During pooled analyses, higher HbA1c was associated with elevated DME risk (standardized mean difference [SMD] 0.29; 95% confidence interval [CI] 0.17–0.41; odds ratio [OR] 1.32; 95% CI 1.19–1.48). Subgroup assessments found no significant association between HbA1c and center-involved DME (SMD 0.3; 95% CI -0.08 to 0.53) or DME associated with advanced diabetic retinopathy stages (SMD -0.14; 95% CI -0.37 to 0.09). Lower lymphocyte count remained significantly associated with DME (SMD -0.24; 95% CI -0.45 to -0.03).

Egger’s test suggested a publication bias in studies assessing HbA1c using odds ratios. Study heterogeneity and observational designs limit causal interpretation.

These findings support the potential contribution of chronic hyperglycemia and systemic inflammatory status to DME risk in T2DM. Further longitudinal research is required to clarify these mechanisms and refine risk stratification across diabetic retinopathy stages.