Soluble Receptor for Advanced Glycation End-Product (sRAGE)/Pentosidine Ratio: A Potential Risk Factor Determinant for Type 2 Diabetic Retinopathy

Zhi Ng,Umah Kuppusamy,Tajunisah Iqbal,Kek Chua

doi:10.3390/ijms14047480

Zhi Ng, Umah Kuppusamy + Show 2 more

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https://doi.org/10.3390/ijms14047480

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Abstract

This study aims to investigate potential diabetic retinopathy (DR) risk factors by evaluating the circulating levels of pentosidine, soluble receptor for advanced glycation end-product (sRAGE), advanced oxidation protein product (AOPP) as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in DR patients. A total of 235 healthy controls, 171 type 2 diabetic without retinopathy (DNR) and 200 diabetic retinopathy (DR) patients were recruited. Plasma was extracted for the estimation of pentosidine, sRAGE, AOPP levels and GPx activity whereas peripheral blood mononuclear cells were disrupted for SOD activity measurement. DNR and DR patients showed significantly higher levels of plasma pentosidine, sRAGE and AOPP but lower GPx and SOD activities when compared to healthy controls. The sRAGE/pentosidine ratio in DR patients was significantly lower than the ratio detected in DNR patients. Proliferative DR patients had significantly higher levels of plasma pentosidine, sRAGE, AOPP and sRAGE/pentosidine ratio than non-proliferative DR patients. High HbA1c level, long duration of diabetes and low sRAGE/pentosidine ratio were determined as the risk factors for DR. This study suggests that sRAGE/pentosidine ratio could serve as a risk factor determinant for type 2 DR as it has a positive correlation with the severity of DR.

Highlights

Diabetes mellitus (DM) is one of the top four most conspicuous non communicable diseases that lead to death worldwide [1]
The patients (DNR and diabetic retinopathy (DR)) had significantly (p < 0.05) higher levels of glycated haemoglobin (HbA1c), total cholesterol, LDL-C and systolic blood pressure (SBP), lower diastolic blood pressure (DBP) and HDL-C/LDL-C ratio when compared to the healthy controls
Our study shows that Soluble RAGE (sRAGE) level and DM duration in DNR patients were positively correlated (Table 2)

Summary

Introduction

Diabetes mellitus (DM) is one of the top four most conspicuous non communicable diseases that lead to death worldwide [1]. The International Diabetes Federation predicts that South East Asia region would have the highest prevalence of DM in 2025 [2] mainly due to the population growth and increase in the rate of obesity. The worldwide rise in DM prevalence will inevitably be accompanied by the increased incidence of irreversible DM associated complications which includes diabetic retinopathy (DR). Hyperglycemia stimulates the increased production of reactive oxygen species through several mechanisms including glucose auto-oxidation, redox imbalance, advanced glycation end products (AGE)-receptor interaction, oxidative phosphorylation, lipooxygenase, cytochrome P450 monooxygenase and nitric oxide synthase [5,6]. The production of reactive oxygen species leads to the depletion of both enzymatic and non-enzymatic antioxidants which inevitably results in cellular damage [7]. The DM environment causes proteins to undergo sequential non-enzymatic glycation with reducing sugar to form AGE [9]

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