Neutrophil–lymphocyte ratio as a reliable marker to predict pre-clinical retinopathy among type 2 diabetic patients

Abstract

Background Diabetic retinopathy is now recognized as a neurovascular in lieu of a microvascular complication. Visual evoked potentials (VEPs) are greatly valuable in detecting early diabetic retinal functional changes before the occurrence of structural damage. Low-grade inflammation plays a fundamental part in the development and progression of retinopathy in diabetics. Detecting diabetic patients with early retinopathy before the occurrence of clinical symptoms provides a window of opportunity to ensure the best prognosis for these eyes. Neutrophil–lymphocyte ratio (NLR) has recently been introduced as a novel marker of inflammation in various diseases. Indeed, the presence of a cheap, available, and reliable marker of inflammation that is capable to detect pre-clinical diabetic retinopathy (P-DR) is crucial for early intervention to retard the progression of ocular damage. As far as we know no previous studies investigated the role of NLR in the detection of P-DR. The aim of this study was to investigate the quality of prediction of NLR in detecting pre-clinical retinopathy in type 2 diabetic patients. Results In this case–control study, VEPs results showed a significant delay in P100 latencies of the patients’ group compared to the control group. According to the VEPs results, the patient group was further subdivided into two: diabetic with VEPs changes (a group with P-DR) and diabetic without VEPs changes. NLR was significantly elevated in patients with P-DR (p < 0.001). NLR cut-off point ≥ 1.97 is able to predict P-DR with 89.29% sensitivity and 84.37% specificity. Linear regression model revealed that NLR is the only independent factor that predicts P-DR. (odds ratio 3.312; 95% confidence interval 1.262–8.696, p = 0.015*. Conclusions Visual evoked potentials have an important role to evaluate the visual pathway in diabetics and to diagnose pre-clinical diabetic retinopathy before the occurrence of structural damage. Neutrophil–lymphocyte ratio is a reliable marker for the detection of pre-clinical diabetic retinopathy with good sensitivity (89.29%) and specificity (84.37%). Finding a reliable available laboratory test to predict P-DR could be of help to save diabetic patients from serious ocular complications.

Changes in Circulating Acylated Ghrelin and Neutrophil Elastase in Diabetic Retinopathy

“…Indeed, here, we demonstrate an increase in neutrophil percentage in DR stages, which negatively correlates with serum AG levels. During DR, neutrophils play a very important role in microangiopathy occurrence and progression, as well as in endothelial cell wall inflammatory processes [28,69], since they secrete proteolytic enzymes involved in endothelial damage [28]. This latter leads to chronic inflammation, which exacerbates microvascular complications, contributing to DR progression [28,70].…”

“…During DR, neutrophils play a very important role in microangiopathy occurrence and progression, as well as in endothelial cell wall inflammatory processes [28,69], since they secrete proteolytic enzymes involved in endothelial damage [28]. This latter leads to chronic inflammation, which exacerbates microvascular complications, contributing to DR progression [28,70]. Indeed, DR patients are characterized by a high serum neutrophil count [71], with a higher neutrophil-lymphocyte ratio [71][72][73].…”

“…These circulating cells play a very important defensive role in the first steps of hyperglycemia-induced acute inflammation, via the degranulation, phagocytosis, and extrusion of neutrophil extracellular traps (NETs) [25]. However, during chronic inflammation, the exacerbated presence of neutrophils and NETs is associated with the thickening of the retinal vascular basement membrane, loss of pericytes, and alterations in the blood-retinal barrier, which, combined, trigger DR microvascular and macrovascular complications [25][26][27][28][29][30][31]. Interestingly, by binding to GHSR-1a on neutrophils, ghrelin is able to promote their apoptosis [22,23], potentially impacting DR microvascular complications in diabetic patients.…”

Changes of Circulating Acylated Ghrelin and Neutrophils Elastase in Diabetic Retinopathy Progression

“…Indeed, here it is demonstrated an increase of neutrophils percentage in DR stages, which negatively correlates with serum AG levels. During DR, neutrophils play a very important role in microangiopathy occurrence and progression, as well as in the endothelial cell wall inflammatory processes [14,50], since they secrete proteolytic enzymes involved in endothelial damage [14]. This latter leads to chronic inflammation which exacerbates microvascular complications, contributing to DR progression [14,51].…”

“…A receptor known as growth hormone secretin receptor 1a (GHSR-1a) and characterized by its higher affinity to acylated form of ghrelin compared to the des-acylated one [11]. Through this receptor, ghrelin is able to promote the apoptosis of neutrophils [12,13], leukocytes highly involved in inflammation and endothelial damage during DR evolution, contributing to DR complications with the extrusion of neutrophil extracellular traps (NETs) [14]. A process called NETosis, worsened by hyperglycemia [15,16] and exacerbated in DR patients [17,18].…”