Sex Differences in Inflammatory Plasma Proteins in Patients With Diabetic Retinopathy.

Purpose: To compare inflammatory protein levels in the plasma of men and women with nonproliferative diabetic retinopathy (NPDR). Methods: We recruited 74 NPDR patients (38 men, 36 women), 82 diabetic patients without retinopathy, and 20 patients without diabetes. Patients with intravitreal injections in the past four weeks, ocular comorbidities, active infection, or systemic vasculitis were excluded. We performed linear regression with plasma concentration of each protein as dependent variable and sex as predictor, adjusting for age, race and ethnicity, smoking status, hemoglobin A1c, insulin use, and diabetes duration. We plotted the concentration of inflammatory proteins against diabetes duration for men and women separately to assess for differences over time. We conducted similar analyses for the control groups. Results: Plasma concentrations of nine inflammatory proteins involved in DR progression were higher in NPDR men than in women. For most of these proteins, the plasma concentration was similar between men and women with fewer years of diabetes and exhibited higher levels in NPDR men with longer durations of diabetes. In those with ≥15 years of diabetes, sex differences in these inflammatory proteins were less apparent. Conclusions: We identified a variety of inflammatory proteins higher in the plasma of male NPDR patients than in female patients. We also found the differences to be more prominent in those who had five to 10 years of diabetes. Translational Relevance: Differences in plasma inflammatory proteins could underlie the clinically observed sex differences in DR, and earlier years of diabetes might be a potential window for closer follow-up and therapeutic intervention.