Sex-Based Analysis of Potential Inflammation-Related Protein Biomarkers in the Aqueous Humor of Patients With Diabetes Mellitus

PURPOSE: To investigate whether men have higher inflammatory protein biomarker concentrations in their aqueous humor (AH) compared with women in groups of patients with varying levels of diabetic disease. METHODS: This cross-sectional study included AH specimens from 59 adult patients comprised of three groups: no diabetes mellitus (DM), DM without diabetic retinopathy (DR), and DM with proliferative diabetic retinopathy (PDR). Protein biomarker concentration values were quantified using a commercial proximity extension assay-based technique. RESULTS: Intersex comparisons of concentration values for each protein biomarker revealed no discoveries in patients with no DM or with PDR. In contrast, 24 discoveries were detected in patients with DM without DR. The mean concentration value for all 24 protein biomarkers was higher in men compared with women. Of these 24 proteins, 12 demonstrated a significant association with sex on multivariate linear regression analysis. The β coefficient results demonstrated a positive association between male sex and concentration value for all 12 of these proteins. CONCLUSIONS: Higher AH concentration levels of several potential biomarkers, including chemokines, proteases, proteins involved in programmed cell death, and a T-cell surface protein, were detected in men with DM with no DR. These findings suggest that men may have a more inflammatory disease phenotype compared with women in this group of patients. TRANSLATIONAL RELEVANCE: The findings of this study help explain differences in epidemiologic patterns of diabetic retinopathy development between men and women.