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Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy.

ABSTRACT: Diabetic patients with a long disease duration usually accompanied complication such as diabetic retinopathy, but in some patients had no complication.We analyzed differences in plasma metabolites according to the presence or absence of diabetic retinopathy (DR) in type 2 diabetic (T2D) patients with disease duration???15 years.A cohort of 183 T2D patients was established. Their biospecimens and clinical information were collected in accordance with the guidelines of the National Biobank of Korea, and the Korean Diabetes Association. DR phenotypes of the subjects were verified by ophthalmologic specialists. Plasma metabolites were analyzed using gas chromatography time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. And these results were analyzed using multivariate statistics.For metabolomic study, propensity score matched case and control subjects were chosen. Mean age of the subjects was 66.4 years and mean T2D duration was 22.2 years. Metabolomic identification revealed various carbohydrates, amino acids, and organic compounds that distinguished between age- and sex-matched non-diabetic controls and T2D subjects. Among these, glutamine and glutamic acid were suggested as the most distinctive metabolites for the presence of DR. Receiver operating characteristics curves showed an excellent diagnostic value of combined (AUC?=?0.739) and the ratio (AUC?=?0.742) of glutamine and glutamic acid for DR. And these results were consistent in validation analyses.Our results imply that plasma glutamine, glutamic acid, and their ratio may be valuable as novel biomarkers for anticipating DR in T2D subjects.

SUBMITTER: Rhee SY

PROVIDER: S-EPMC6013531 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy.

Rhee Sang Youl SY Jung Eun Sung ES Park Hye Min HM Jeong Su Jin SJ Kim Kiyoung K Chon Suk S Yu Seung-Young SY Woo Jeong-Taek JT Lee Choong Hwan CH

Metabolomics : Official journal of the Metabolomic Society 20180621 7

<h4>Introduction</h4>Diabetic patients with a long disease duration usually accompanied complication such as diabetic retinopathy, but in some patients had no complication.<h4>Objectives</h4>We analyzed differences in plasma metabolites according to the presence or absence of diabetic retinopathy (DR) in type 2 diabetic (T2D) patients with disease duration ≥ 15 years.<h4>Methods</h4>A cohort of 183 T2D patients was established. Their biospecimens and clinical information were collected in accord ...[more]

PMID: 29950956

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Project description:ObjectiveDiabetic retinopathy (DR) is a common diabetic microvascular complication and a major cause of acquired vision loss. Finding effective biomarkers for the early identification and diagnosis of DR is crucial. This study aimed to comprehensively evaluate the accuracy of microRNAs (miRNAs) in the diagnosis of DR via a meta-analysis of previously published diagnostic studies. This study has been registered on the PROSPERO website, with the number CRD42022323238.MethodsWe searched PubMed, Cochrane Library, Embase, Web of Science, China Wanfang database, and China Knowledge Network database to identify relevant articles published from the time of database creation to April 10, 2022. Stata 14.0 software was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the summary receiver operating characteristic (ROC) curve to assess the accuracy of miRNAs in the diagnosis of DR. Heterogeneity between studies was assessed using Cochran-Q test and I2 statistic for quantitative analysis. The random-effect model was selected due to significant heterogeneity. Subgroup analysis and regression analysis were also performed to determine the potential sources of heterogeneity.ResultsWe included 25 articles detailing 52 studies with 1987 patients with DR and 1771 non-DR controls. The findings demonstrated overall sensitivity (0.82, 95% CI: 0.78 ~ 0.85), specificity (0.84, 95% CI: 0.81 ~ 0.86), PLR (5.0, 95% CI: 4.2 ~ 5.9), NLR (0.22, 95% CI: 0.18 ~ 0.26), and the area under the summary ROC curve (0.90, 95% CI: 0.87 ~ 0.92). Furthermore, we performed subgroup analysis and found that panels of multiple miRNAs could enhance the pooled sensitivity (sensitivity, specificity, and AUC values were 0.89, 0.87, and 0.94, respectively).ConclusionThe meta-analysis showed that miRNAs can be used as potential diagnostic markers for DR, with high accuracy of diagnoses observed with the detection of miRNAs in plasma and serum.

Project description:Purpose: To reveal molecular mechanisms of diabetic retinopathy (DR) in Asians and facilitate the identification of new therapeutic targets through untargeted metabolomics. To determine the differences in serum metabolites and metabolic pathways between different stages of diabetic retinopathy in patients with type 2 diabetic mellitus (T2DM) and proliferative DR (PDR) and non-proliferative DR (NPDR) and identify differential metabolites between T2DM and DR (NPDR and PDR) patients. Methods: This prospective observational registration study described the differential metabolites between 45 T2DM patients and 15 control cases with no significant differences in clinical characteristics. Their biospecimens and clinical information were collected and recorded in their medical reports. DR phenotypes of the subjects were verified by retina specialists. Serum metabolites were analyzed using high-resolution mass spectrometry with liquid chromatography. Untargeted metabolomics was performed on serum samples from 15 T2DM patients, 15 non-proliferative diabetic retinopathy patients, 15 proliferative diabetic retinopathy patients, and 15 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis (PLS-DA), hierarchical clustering analysis (HCA), and generalized linear regression models. Result: Through untargeted metabolomics, 931 features (523 in positive and 408 in negative modes) with 102 common metabolites highly relevant to the presence of DR were detected. In the adjusted analysis, 67 metabolic features differed significantly between T2DM and NPDR patients. Pathway analysis revealed alterations in metabolisms of amino acids and fatty acids. Glutamate, phosphatidylcholine, and 13-hydroperoxyoctadeca-9,11-dienoic acid (13-PHODE) were key contributors to these pathway differences. A total of 171 features distinguished PDR patients from T2DM patients, and pathway analysis revealed alterations in amino acid metabolism, fatty acid metabolism, nitrogen metabolism, and tricarboxylic acid cycle. Aspartate, glutamate, glutamine, ornithine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, citrate, succinate, N-(L-arginino)succinate, 2-oxoglutarate, 13-hydroperoxyoctadeca-9,11-dienoic acid, methionine, lysine, threonine, phenylalanine, N(pi)-methyl-l-histidine, phosphatidylcholine, and linoleate were major contributors to the pathway differences. Between NPDR patients and PDR patients, there were 79 significant differential metabolites. Enrichment pathway analysis showed changes in amino acid metabolism, fatty acid metabolism, pantothenate, and CoA biosynthesis. Aspartate, glutamine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, pantothenate, dihomo-gamma-linolenate, docosahexaenoic acid, and icosapentaenoic acid were key factors for the differences of these pathways. Conclusion: This study demonstrated that the pathways of arginine biosynthesis metabolism, linoleic acid metabolism, alanine, aspartate, and glutamate metabolism, as well as d-glutamine and d-glutamate metabolism, were dysregulated in DR patients of the Asian population. Increased levels of glutamate, aspartate, glutamine, N-acetyl-l-glutamate, and N-acetyl-l-aspartate and decreased levels of dihomo-gamma-linolenate, docosahexaenoic, and icosapentaenoic were considered as the metabolic profile that could distinguish PDR from NPDR in Asians. Phosphatidylcholine and 13-PHODE were identified as two major novel metabolite markers in advanced stages of DR in our study.

Project description:BackgroundProliferative 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.MethodsA 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).ResultsThe 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.ConclusionsThis 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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Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy.

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Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy.

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