ENDOTHELIAL MONOCYTE-ACTIVATING POLYPEPTIDE-II AS A POSSIBLE DIAGNOSTIC AND PROGNOSTIC FACTOR OF DIABETIC RETINOPATHY

Background. Endothelial dysfunction is involved in the pathogenesis of microvascular complications of type 2 diabetes mellitus. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a multifunctional polypeptide with proinflammatory and antiangiogenic activity, which is associated with the development of diabetic retinopathy (DR). Aim: to determine the blood content of EMAP-II at different stages of DR and the possibility of its use as a biomarker of DR progression. Material and methods. 136 patients with type 2 diabetes were examined, who were divided into groups: 1st - with non-proliferative (NPDR, 60 eyes), 2nd - with preproliferative DR (PPDR; 42 eyes) and 3rd - with proliferative DR (PDR; 34 eyes). Patients were examined and treated for 2 years. 25 patients who did not have diabetes were involved as controls. EMAP-II was determined in blood serum by enzyme-linked immunosorbent assay. Analysis of the study results was carried out in the EZR v.1.54 package (Austria). Results. In patients with DR and type 2 diabetes, a significant increase in the blood content of EMAP-II was found compared to the control. In NPDR, it exceeded the control level by 2.5 times, in PPDR – by 4.6 times, in PDR – by 6.1 times (p<0.001 for all comparisons). Intergroup comparisons were also statistically significant (p<0.05), which confirmed the progressive nature of the increase in EMAP-II in the DR development. The cut-off levels of EMAP-II were determined: for NPDR they were from 2.186 ng/ml to 5.66 ng/ml, in PPDR – from 5.67 ng/ml to 7.565 ng/ml and in PDR – more than 7.565 ng/ml. The overall prediction accuracy was 82.0% (95% CI 75.2-87.6%). EMAP-II levels were significantly correlated with fasting blood glucose (r=0.207), central retinal thickness (r=0.578) and volume (r=0.554), glycated hemoglobin (r=0.699), total cholesterol (r=0.442), high-density lipoprotein (r=0.25), low-density lipoprotein (r=0.39) and very low-density lipoprotein (r=0.515), and triglycerides (r=0.359; p<0.05 for all cases). The risk of DR progression after 2 years of observation increased 2.0-fold with increasing EMAP-II levels in the blood (p<0.001; OR=2.0; 95% CI 1.6-2.49). The area under the curve of the operating characteristics of the prediction AUC=0.88 (95% CI 0.81-0.93), the sensitivity of the model was 70.9%, specificity – 89.5%. Conclusion. Thus, it was established that EMAP-II is one of key factor in the DR pathogenesis, which is closely related to phenotypic manifestations, and its content in the blood is a biomarker of the stage of DR and its progression.