Relationship Between the Degree of Diabetic Retinopathy and Serum Fractalkine (CX3CL1) in Patients with Type 2 Diabetes: A Single-Center Cross-Sectional Study

TL;DR

This study found that higher levels of a protein called fractalkine in the blood are linked to the presence and severity of diabetic retinopathy in type 2 diabetes patients.

Contribution

The study demonstrates that serum fractalkine is independently associated with diabetic retinopathy after adjusting for traditional risk factors.

Findings

Serum fractalkine levels were significantly higher in patients with diabetic retinopathy compared to those without.

Fractalkine levels increased with the severity of non-proliferative diabetic retinopathy.

Serum fractalkine showed moderate diagnostic performance for detecting diabetic retinopathy and severe non-proliferative retinopathy.

Abstract

Background and Objectives: Diabetic retinopathy (DR) is a leading microvascular complication of type 2 diabetes (T2D). Fractalkine (CX3CL1), a chemokine involved in inflammation, angiogenesis, and microglial activation, may play a role in DR pathogenesis. This study investigated the association between serum fractalkine levels, the presence of DR, and disease severity. Materials and Methods: In this cross-sectional study, 140 adults with T2D were classified as non-DR (n = 32) or DR (n = 108) according to ICDR and ETDRS criteria; DR cases were further categorized into NPDR (n = 76) and PDR (n = 32), with NPDR staged as mild, moderate, or severe. Serum fractalkine concentrations were measured using ELISA. Results: Serum fractalkine levels were significantly higher in patients with DR than in those without retinopathy (0.7 vs. 0.4 ng/mL, p < 0.001). Within NPDR stages, fractalkine levels were highest in severe NPDR (p = 0.004). No significant fractalkine difference was found between NPDR and PDR groups. In multivariable analysis, serum fractalkine (OR 10.2; 95% CI 1.2–89.6; p = 0.036) remained independently associated with the presence of DR. For identifying DR, fractalkine yielded an AUC of 0.736; the optimal cut-off of 0.455 ng/mL provided 81.5% sensitivity and 56.3% specificity. In distinguishing severe NPDR, fractalkine demonstrated strong diagnostic performance (AUC = 0.784), with a cut-off of 0.720 ng/mL yielding 100% sensitivity and 61.9% specificity. Conclusions: Serum fractalkine is significantly associated with both the presence and severity of DR and remains independently associated with retinopathy after adjustment for traditional risk markers. Serum fractalkine may offer complementary systemic information in automated and AI-based retinal screening. These findings are exploratory and hypothesis-generating, and prospective studies are required to determine the clinical relevance of serum fractalkine in DR.

Figures