Abstract

BackgroundsDiabetic retinopathy (DR), the main retinal vascular complication of DM, is the leading cause of visual impairment and blindness among working-age people worldwide. The aim of this study was to investigate the difference of plasma metabolic profiles in patients with DR to better understand the mechanism of this disease and disease progression.MethodsWe used ultrahigh-performance liquid Q-Exactive mass spectrometry and multivariate statistical analyses to conduct a comprehensive analysis of plasma metabolites in a population with DR and proliferative DR (PDR). A risk score based on the level of the selected metabolite was established and evaluated using the least absolute shrinkage and selection operator regularization logistic regression (LASSO-LR) based machine learning model.Results22 differentially expressed metabolites which belonged to different metabolic pathway were identified and confirmed to be associated with the occurrence of DR. A risk score based on the level of the selected metabolite pseudouridine was established and evaluated to strongly associated with the occurrence of DR. Four circulating plasma metabolites (pseudouridine, glutamate, leucylleucine and N-acetyltryptophan) were identified to be differentially expressed between patients with PDR and other patients, and a risk score formula based on these plasma metabolites was developed and assessed to be significantly related to PDR.ConclusionsOur work highlights the possible use of the risk score assessment based on the plasma metabolites not only reveal in the early diagnosis of DR and PDR but also assist in enhancing current therapeutic strategies in the clinic.

Highlights

  • In both developing and developed countries, the prevalence of diabetes mellitus (DM) is rising

  • A risk score based on the level of the selected metabolite pseudouridine was established and evaluated using the least absolute shrinkage and selection operator regularization logistic regression (LASSO-LR) based machine learning method, and this score was strongly associated with the occurrence of Diabetic retinopathy (DR)

  • Four circulating plasma metabolites were identified to be differentially expressed between patients with proliferative DR (PDR) and other patients, and a risk score formula based on these plasma metabolites was developed and assessed to be significantly related to the severity of DR

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Summary

Introduction

In both developing and developed countries, the prevalence of diabetes mellitus (DM) is rising. The proportion was reported to be less than 1% in the 1980s in China, while a series of large-scale and well-conducted population surveys have shown that the prevalence has risen sharply to 9-12% in the past few years, with more than one million persons affected [2, 3]. Diabetic retinopathy (DR), the main retinal vascular complication of DM, is the leading cause of visual impairment and blindness among working-age people worldwide [4]. The existence of DR suggests an increased risk of life-threatening systemic vascular complications [5, 6]. By 2010, worldwide, DM-related eye disease contributed to the fifth most common cause of moderate-to-severe vision loss and blindness, accounting for nearly four million cases of visual impairment and more than eight hundred thousand cases of blindness [7]

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