Plasma metabolomic profiling of proliferative diabetic retinopathy

Abstract 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 path...

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Main Authors: Xiao-Rong Zhu, Fang-yuan Yang, Jing Lu, Hui-rong Zhang, Ran Sun, Jian-Bo Zhou, Jin-Kui Yang
Format: Article
Language:English
Published: BMC 2019-05-01
Series:Nutrition & Metabolism
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12986-019-0358-3
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author Xiao-Rong Zhu
Fang-yuan Yang
Jing Lu
Hui-rong Zhang
Ran Sun
Jian-Bo Zhou
Jin-Kui Yang
author_facet Xiao-Rong Zhu
Fang-yuan Yang
Jing Lu
Hui-rong Zhang
Ran Sun
Jian-Bo Zhou
Jin-Kui Yang
author_sort Xiao-Rong Zhu
collection DOAJ
description Abstract 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.
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spelling doaj.art-f78659ed62134280b866958a23a9ec942022-12-22T01:30:58ZengBMCNutrition & Metabolism1743-70752019-05-0116111110.1186/s12986-019-0358-3Plasma metabolomic profiling of proliferative diabetic retinopathyXiao-Rong Zhu0Fang-yuan Yang1Jing Lu2Hui-rong Zhang3Ran Sun4Jian-Bo Zhou5Jin-Kui Yang6Department of Endocrinology, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Endocrinology, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Endocrinology, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Endocrinology, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Endocrinology, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Endocrinology, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Endocrinology, Beijing Tongren Hospital, Capital Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s12986-019-0358-3Type 2 diabetesProliferative diabetic retinopathyMetabolomicsMetabolic profilingLC-MS
spellingShingle Xiao-Rong Zhu
Fang-yuan Yang
Jing Lu
Hui-rong Zhang
Ran Sun
Jian-Bo Zhou
Jin-Kui Yang
Plasma metabolomic profiling of proliferative diabetic retinopathy
Nutrition & Metabolism
Type 2 diabetes
Proliferative diabetic retinopathy
Metabolomics
Metabolic profiling
LC-MS
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 Type 2 diabetes
Proliferative diabetic retinopathy
Metabolomics
Metabolic profiling
LC-MS
url http://link.springer.com/article/10.1186/s12986-019-0358-3
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