The Usefulness of Serum Biomarkers in the Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial

Abstract

The main aim of this study was to evaluate the ability of serum biomarkers to predict the worsening of retinal neurodysfunction in subjects with type 2 diabetes. For this purpose, we measured selected molecules (N-epsilon-carboxy methyl lysine (CML), laminin P1 (Lam-P1), and asymmetric dimethylarginine (ADMA)) in the serum of 341 participants of the EUROCONDOR study at baseline, 24, and 48 weeks. Retinal neurodysfunction was assessed by measuring implicit time (IT) using multifocal electroretinography, and structural changes were examined by spectral domain–optical coherence tomography. The values of IT at baseline were directly correlated with baseline serum concentrations of CML (r = 0.135, p = 0.013). Furthermore, in the placebo group, increase in CML concentration throughout follow-up correlated with the IT (r = 0.20; p = 0.03). Baseline serum levels of CML also correlated with macular retinal thickness (RT) (r = 0.231; p < 0.001). Baseline Lam-P1 levels correlated with the increase of the RT at the end of follow-up in the placebo group (r = 0.22; p = 0.016). We provide evidence that CML may be a biomarker of both retinal neurodysfunction and RT, whereas Lam-P1 was associated with RT only. Therefore, circulating levels of these molecules could provide a complementary tool for monitoring the early changes of diabetic retinopathy (DR).

Semaglutide-eye-catching results

“…The Consortium for the Early Treatment of DR (EUROCONDOR) study failed to find any signs of neurodegeneration in a significant percentage of patients with microangiopathic retinal lesions[ 66 , 67 ]. However, as already mentioned before, neurodegeneration has been proposed as a hallmark of DR[ 68 - 70 ].…”

Circulating Biomarkers to Predict Diabetic Retinopathy in Patients with Diabetic Kidney Disease

“…Among the AGEs, the concentration of serum N-epsilon-carboxy methyl lysine (CML) and pentosidine markedly increased in both DR and DKD, especially in subjects with PDR compared to mild or severe NPDR [ 23 ]. In the EUROCONDOR trial, serum CML concentration was linked to retinal thickness and neurodysfunction, allowing for the identification of early abnormal DR findings and monitoring of its progression [ 24 ]. Elevated blood levels of RAGEs in T2DM patients with PDR compared to subjects with NPDR or without DR have also been described [ 25 ].…”

“…Previous studies have suggested the use of circulating laminin-P1 as an early marker for DR presence and severity [ 57 ]. Evidence from the EUROCONDOR showed that the baseline serum laminin-P1 was correlated to the increase in the ganglion cell layer-inner plexiform layer and overall retinal thickness [ 24 ]. Moreover, laminin-P1 was reduced in patients who were given somatostatin, indicating its usefulness in monitoring the therapeutic effectiveness of early DR management.…”

Understanding Neurodegeneration from a Clinical and Therapeutic Perspective in Early Diabetic Retinopathy

“…An ancillary study from EUROCONDOR [85] aimed to test some circulating molecules in predicting the worsening of retinal neurodysfunction. The selected molecules reflected potential biomarkers for neurodysfunction based on the NVU impairment pathogenic mechanisms.…”