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Plasma metabolomic profiling of proliferative diabetic retinopathy

BACKGROUND: Proliferative diabetic retinopathy (PDR), a sight-threatening retinopathy, is the leading cause of irreversible blindness in adults. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop PDR, suggesting the existence of other potential pathogenic f...

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Autores principales: Zhu, Xiao-Rong, Yang, Fang-yuan, Lu, Jing, Zhang, Hui-rong, Sun, Ran, Zhou, Jian-Bo, Yang, Jin-Kui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540396/
https://www.ncbi.nlm.nih.gov/pubmed/31160916
http://dx.doi.org/10.1186/s12986-019-0358-3
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author Zhu, Xiao-Rong
Yang, Fang-yuan
Lu, Jing
Zhang, Hui-rong
Sun, Ran
Zhou, Jian-Bo
Yang, Jin-Kui
author_facet Zhu, Xiao-Rong
Yang, Fang-yuan
Lu, Jing
Zhang, Hui-rong
Sun, Ran
Zhou, Jian-Bo
Yang, Jin-Kui
author_sort Zhu, Xiao-Rong
collection PubMed
description BACKGROUND: Proliferative diabetic retinopathy (PDR), a sight-threatening retinopathy, is the leading cause of irreversible blindness in adults. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop PDR, suggesting the existence of other potential pathogenic factors underlying PDR. This study aimed to investigate the plasma metabotype of patients with PDR and to identify novel metabolite markers for PDR. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of diabetic retinopathy. METHODS: A total of 1024 patients with type 2 diabetes were screened. To match clinical parameters between case and control subjects, patients with PDR (PDR, n = 21) or those with a duration of diabetes of ≥10 years but without diabetic retinopathy (NDR, n = 21) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS). RESULTS: The distinct metabolites between PDR and NDR groups were significantly enriched in 9 KEGG pathways (P < 0.05, impact > 0.1), namely, alanine, aspartate and glutamate metabolism, caffeine metabolism, beta-alanine metabolism, purine metabolism, cysteine and methionine metabolism, sulfur metabolism, sphingosine metabolism, and arginine and proline metabolism. A total of 63 altered metabolites played important roles in these pathways. Finally, 4 metabolites were selected as candidate biomarkers for PDR, namely, fumaric acid, uridine, acetic acid, and cytidine. The area under the curve for these biomarkers were 0.96, 0.95, 1.0, and 0.95, respectively. CONCLUSIONS: This study suggested that impairment in the metabolism of pyrimidines, arginine and proline were identified as metabolic dysregulation associated with PDR. And fumaric acid, uridine, acetic acid, and cytidine might be potential biomarkers for PDR. Fumaric acid was firstly reported as a novel metabolite marker with no prior reports of association with diabetes or diabetic retinopathy, which might provide insights into potential new pathogenic pathways for diabetic retinopathy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12986-019-0358-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-65403962019-06-03 Plasma metabolomic profiling of proliferative diabetic retinopathy Zhu, Xiao-Rong Yang, Fang-yuan Lu, Jing Zhang, Hui-rong Sun, Ran Zhou, Jian-Bo Yang, Jin-Kui Nutr Metab (Lond) Research BACKGROUND: Proliferative diabetic retinopathy (PDR), a sight-threatening retinopathy, is the leading cause of irreversible blindness in adults. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop PDR, suggesting the existence of other potential pathogenic factors underlying PDR. This study aimed to investigate the plasma metabotype of patients with PDR and to identify novel metabolite markers for PDR. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of diabetic retinopathy. METHODS: A total of 1024 patients with type 2 diabetes were screened. To match clinical parameters between case and control subjects, patients with PDR (PDR, n = 21) or those with a duration of diabetes of ≥10 years but without diabetic retinopathy (NDR, n = 21) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS). RESULTS: The distinct metabolites between PDR and NDR groups were significantly enriched in 9 KEGG pathways (P < 0.05, impact > 0.1), namely, alanine, aspartate and glutamate metabolism, caffeine metabolism, beta-alanine metabolism, purine metabolism, cysteine and methionine metabolism, sulfur metabolism, sphingosine metabolism, and arginine and proline metabolism. A total of 63 altered metabolites played important roles in these pathways. Finally, 4 metabolites were selected as candidate biomarkers for PDR, namely, fumaric acid, uridine, acetic acid, and cytidine. The area under the curve for these biomarkers were 0.96, 0.95, 1.0, and 0.95, respectively. CONCLUSIONS: This study suggested that impairment in the metabolism of pyrimidines, arginine and proline were identified as metabolic dysregulation associated with PDR. And fumaric acid, uridine, acetic acid, and cytidine might be potential biomarkers for PDR. Fumaric acid was firstly reported as a novel metabolite marker with no prior reports of association with diabetes or diabetic retinopathy, which might provide insights into potential new pathogenic pathways for diabetic retinopathy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12986-019-0358-3) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-28 /pmc/articles/PMC6540396/ /pubmed/31160916 http://dx.doi.org/10.1186/s12986-019-0358-3 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhu, Xiao-Rong
Yang, Fang-yuan
Lu, Jing
Zhang, Hui-rong
Sun, Ran
Zhou, Jian-Bo
Yang, Jin-Kui
Plasma metabolomic profiling of proliferative diabetic retinopathy
title Plasma metabolomic profiling of proliferative diabetic retinopathy
title_full Plasma metabolomic profiling of proliferative diabetic retinopathy
title_fullStr Plasma metabolomic profiling of proliferative diabetic retinopathy
title_full_unstemmed Plasma metabolomic profiling of proliferative diabetic retinopathy
title_short Plasma metabolomic profiling of proliferative diabetic retinopathy
title_sort plasma metabolomic profiling of proliferative diabetic retinopathy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540396/
https://www.ncbi.nlm.nih.gov/pubmed/31160916
http://dx.doi.org/10.1186/s12986-019-0358-3
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