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Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia

Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenita...

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Autores principales: Darenskaya, Marina, Chugunova, Elena, Kolesnikov, Sergey, Semenova, Natalya, Michalevich, Isay, Nikitina, Olga, Lesnaya, Anastasya, Kolesnikova, Lyubov
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785540/
https://www.ncbi.nlm.nih.gov/pubmed/36557320
http://dx.doi.org/10.3390/metabo12121282
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author Darenskaya, Marina
Chugunova, Elena
Kolesnikov, Sergey
Semenova, Natalya
Michalevich, Isay
Nikitina, Olga
Lesnaya, Anastasya
Kolesnikova, Lyubov
author_facet Darenskaya, Marina
Chugunova, Elena
Kolesnikov, Sergey
Semenova, Natalya
Michalevich, Isay
Nikitina, Olga
Lesnaya, Anastasya
Kolesnikova, Lyubov
author_sort Darenskaya, Marina
collection PubMed
description Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30–300 mg/day and albumin/creatinine ratio 3–30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.
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spelling pubmed-97855402022-12-24 Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia Darenskaya, Marina Chugunova, Elena Kolesnikov, Sergey Semenova, Natalya Michalevich, Isay Nikitina, Olga Lesnaya, Anastasya Kolesnikova, Lyubov Metabolites Article Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30–300 mg/day and albumin/creatinine ratio 3–30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures. MDPI 2022-12-16 /pmc/articles/PMC9785540/ /pubmed/36557320 http://dx.doi.org/10.3390/metabo12121282 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Darenskaya, Marina
Chugunova, Elena
Kolesnikov, Sergey
Semenova, Natalya
Michalevich, Isay
Nikitina, Olga
Lesnaya, Anastasya
Kolesnikova, Lyubov
Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia
title Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia
title_full Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia
title_fullStr Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia
title_full_unstemmed Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia
title_short Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia
title_sort receiver operator characteristic (roc) analysis of lipids, proteins, dna oxidative damage, and antioxidant defense in plasma and erythrocytes of young reproductive-age men with early stages of type 1 diabetes mellitus (t1dm) nephropathy in the irkutsk region, russia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785540/
https://www.ncbi.nlm.nih.gov/pubmed/36557320
http://dx.doi.org/10.3390/metabo12121282
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