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Antioxidants
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Role of Oxidative Stress in Diabetes and Complications: From Biomarkers...
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Role of Oxidative Stress in Diabetes and Complications: From Biomarkers to Therapeutic Targets

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 28099

Special Issue Editor

Prof. Dr. Francesca Santilli

E-Mail Website1 Website2
Guest Editor
Department of Medicine and Aging, Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy
Interests: platelet activation; platelet inhibition; diabetes; obesity; aspirin; oxidative stress

Special Issue Information

Dear Colleagues,

Oxidative stress is a phenomenon caused by an uncontrolled imbalance between production and accumulation of reactive oxygen species (ROS) and the ability of a biological system to detoxify these reactive products. A growing body of evidence suggests a biological link between ROS intracellular damage and the onset of insulin resistance, β-cell dysfunction, and chronic hyperglycemia on the one hand, and the occurrence of diabetic vascular complications on the other.

Different types of oxidative-stress-related molecules have been identified, such as the F2-isoprostanes 8-iso-prostaglandin (PG)F2α and plasma AGE/RAGE axis, both involved in platelet activation, endothelial dysfunction, and thrombus formation in the setting of diabetes. Some of these are emerging as valuable biomarkers to provide important information about the efficacy of the antidiabetic treatment, guiding the selection of the most effective drugs/dosing regimens, or as potential therapeutic targets, such as microRNAs. Given the important role of oxidative stress in the pathogenesis of many clinical conditions, antioxidant therapy may positively affect the natural history of these diseases, but further investigation is needed to evaluate the real efficacy of related therapeutic interventions.

Prof. Francesca Santilli
Guest Editor

Manuscript Submission Information

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Keywords

  • Oxidative stress
  • Diabetes
  • Cardiovascular risk

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Published Papers (6 papers)

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Research

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12 pages, 864 KiB  
Article
Effects of Non-Surgical Periodontal Treatment on Reactive Oxygen Metabolites and Glycemic Control in Diabetic Patients with Chronic Periodontitis
by Simone Marconcini, Enrica Giammarinaro, Saverio Cosola, Giacomo Oldoini, Annamaria Genovesi and Ugo Covani
Antioxidants 2021, 10(7), 1056; https://doi.org/10.3390/antiox10071056 - 30 Jun 2021
Cited by 18 | Viewed by 3636
Abstract
Periodontal infection may contribute to poor glycemic control and systemic inflammation in diabetic patients. The aim of the present study is to evaluate the efficacy of non-surgical periodontal treatment in diabetic patients by measuring oxidative stress outcomes. Sixty diabetic patients with periodontitis were [...] Read more.
Periodontal infection may contribute to poor glycemic control and systemic inflammation in diabetic patients. The aim of the present study is to evaluate the efficacy of non-surgical periodontal treatment in diabetic patients by measuring oxidative stress outcomes. Sixty diabetic patients with periodontitis were enrolled, treated with scaling and full-mouth disinfection, and randomly prescribed chlorhexidine mouthwash, antioxidant mouthwash, or ozone therapy. Reactive oxygen metabolites (ROMs), periodontal parameters, and glycated hemoglobin were measured at baseline and then at 1, 3, and 6 months after. At baseline, all patients presented with pathologic levels of plasmatic ROM (388 ± 21.36 U CARR), higher than the normal population. Probing depth, plaque index, and bleeding on probing values showed significant clinical improvements after treatment, accompanied by significant reductions of plasma ROM levels (p < 0.05). At the 6-month evaluation, the mean ROM relapsed to 332 ± 31.76 U CARR. Glycated hemoglobin decreased significantly (∆ = −0.52 units) after treatment. Both the test groups showed longer-lasting improvements of periodontal parameters. In diabetic patients, periodontal treatment was effective at reducing plasma ROM, which is an indicator of systemic oxidative stress and inflammation. The treatment of periodontal infection might facilitate glycemic control and decrease systemic inflammation. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Diabetes and Complications: From Biomarkers to Therapeutic Targets)
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12 pages, 6905 KiB  
Article
Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research
by Cornelia G. Bala, Adriana Rusu, Dana Ciobanu, Camelia Bucsa and Gabriela Roman
Antioxidants 2021, 10(4), 610; https://doi.org/10.3390/antiox10040610 - 15 Apr 2021
Cited by 31 | Viewed by 3904
Abstract
Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic [...] Read more.
Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic changes associated with increased oxidative stress, as assessed by nitrotyrosine levels, in type 2 diabetes (T2DM). Serum samples of 80 patients with insulin-treated T2DM are analyzed by AA-targeted metabolomics using ultrahigh-performance liquid chromatography/mass spectrometry. Patients are divided into two groups based on their nitrotyrosine levels: the highest level of oxidative stress (Q4 nitrotyrosine) and lower levels (Q1–Q3 nitrotyrosine). The identification of biomarkers is performed in MetaboAnalyst version 5.0 using a t-test corrected for false discovery rate, unsupervised principal component analysis and supervised partial least-squares discriminant analysis (PLS-DA). Four AAs have significantly different levels between the groups for highest and lower oxidative stress. Cysteine, phenylalanine and tyrosine are substantially increased while citrulline is decreased (p-value <0.05 and variable importance in the projection [VIP] >1). Corresponding pathways that might be disrupted in patients with high oxidative stress are phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, phenylalanine metabolism, cysteine and methionine metabolism and tyrosine metabolism. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Diabetes and Complications: From Biomarkers to Therapeutic Targets)
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24 pages, 9486 KiB  
Article
Visceral Adipose Tissue of Prediabetic and Diabetic Females Shares a Set of Similarly Upregulated microRNAs Functionally Annotated to Inflammation, Oxidative Stress and Insulin Signaling
by Justyna Strycharz, Adam Wróblewski, Andrzej Zieleniak, Ewa Świderska, Tomasz Matyjas, Monika Rucińska, Lech Pomorski, Piotr Czarny, Janusz Szemraj, Józef Drzewoski and Agnieszka Śliwińska
Antioxidants 2021, 10(1), 101; https://doi.org/10.3390/antiox10010101 - 12 Jan 2021
Cited by 21 | Viewed by 3455
Abstract
Hypertrophic and hypoxic visceral adipose tissue (VAT) secretes proinflammatory cytokines promoting insulin resistance (IR), prediabetes and type 2 diabetes (T2DM) microRNAs (miRNAs) are markers of metabolic disorders regulating genes critical for e.g., inflammation, glucose metabolism, and antioxidant defense, with raising diagnostic value. The [...] Read more.
Hypertrophic and hypoxic visceral adipose tissue (VAT) secretes proinflammatory cytokines promoting insulin resistance (IR), prediabetes and type 2 diabetes (T2DM) microRNAs (miRNAs) are markers of metabolic disorders regulating genes critical for e.g., inflammation, glucose metabolism, and antioxidant defense, with raising diagnostic value. The aim of the current study was to evaluate whether hyperglycemia is able to affect the expression of selected miRNAs in VAT of prediabetic (IFG) and diabetic (T2DM) patients vs. normoglycemic (NG) subjects using qPCR. Statistical analyses suggested that miRNAs expression could be sex-dependent. Thus, we determined 15 miRNAs as differentially expressed (DE) among NG, T2DM, IFG females (miR-10a-5p, let-7d-5p, miR-532-5p, miR-127-3p, miR-125b-5p, let-7a-5p, let-7e-5p, miR-199a-3p, miR-365a-3p, miR-99a-5p, miR-100-5p, miR-342-3p, miR-146b-5p, miR-204-5p, miR-409-3p). Majority of significantly changed miRNAs was similarly upregulated in VAT of female T2DM and IFG patients in comparison to NG subjects, positively correlated with FPG and HbA1c, yet, uncorrelated with WHR/BMI. Enrichment analyses indicated involvement of 11 top DE miRNAs in oxidative stress, inflammation and insulin signaling. Those miRNAs expression changes could be possibly associated with low-grade chronic inflammation and oxidative stress in VAT of hyperglycemic subjects. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Diabetes and Complications: From Biomarkers to Therapeutic Targets)
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Review

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19 pages, 982 KiB  
Review
MicroRNAs and Oxidative Stress: An Intriguing Crosstalk to Be Exploited in the Management of Type 2 Diabetes
by Teresa Vezza, Aranzazu M. de Marañón, Francisco Canet, Pedro Díaz-Pozo, Miguel Marti, Pilar D’Ocon, Nadezda Apostolova, Milagros Rocha and Víctor M. Víctor
Antioxidants 2021, 10(5), 802; https://doi.org/10.3390/antiox10050802 - 19 May 2021
Cited by 18 | Viewed by 4024
Abstract
Type 2 diabetes is a chronic disease widespread throughout the world, with significant human, social, and economic costs. Its multifactorial etiology leads to persistent hyperglycemia, impaired carbohydrate and fat metabolism, chronic inflammation, and defects in insulin secretion or insulin action, or both. Emerging [...] Read more.
Type 2 diabetes is a chronic disease widespread throughout the world, with significant human, social, and economic costs. Its multifactorial etiology leads to persistent hyperglycemia, impaired carbohydrate and fat metabolism, chronic inflammation, and defects in insulin secretion or insulin action, or both. Emerging evidence reveals that oxidative stress has a critical role in the development of type 2 diabetes. Overproduction of reactive oxygen species can promote an imbalance between the production and neutralization of antioxidant defence systems, thus favoring lipid accumulation, cellular stress, and the activation of cytosolic signaling pathways, and inducing β-cell dysfunction, insulin resistance, and tissue inflammation. Over the last few years, microRNAs (miRNAs) have attracted growing attention as important mediators of diverse aspects of oxidative stress. These small endogenous non-coding RNAs of 19–24 nucleotides act as negative regulators of gene expression, including the modulation of redox signaling pathways. The present review aims to provide an overview of the current knowledge concerning the molecular crosstalk that takes place between oxidative stress and microRNAs in the physiopathology of type 2 diabetes, with a special emphasis on its potential as a therapeutic target. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Diabetes and Complications: From Biomarkers to Therapeutic Targets)
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23 pages, 3167 KiB  
Review
Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future
by Carla Iacobini, Martina Vitale, Carlo Pesce, Giuseppe Pugliese and Stefano Menini
Antioxidants 2021, 10(5), 727; https://doi.org/10.3390/antiox10050727 - 5 May 2021
Cited by 88 | Viewed by 6625
Abstract
Twenty years have passed since Brownlee and colleagues proposed a single unifying mechanism for diabetic complications, introducing a turning point in this field of research. For the first time, reactive oxygen species (ROS) were identified as the causal link between hyperglycemia and four [...] Read more.
Twenty years have passed since Brownlee and colleagues proposed a single unifying mechanism for diabetic complications, introducing a turning point in this field of research. For the first time, reactive oxygen species (ROS) were identified as the causal link between hyperglycemia and four seemingly independent pathways that are involved in the pathogenesis of diabetes-associated vascular disease. Before and after this milestone in diabetes research, hundreds of articles describe a role for ROS, but the failure of clinical trials to demonstrate antioxidant benefits and some recent experimental studies showing that ROS are dispensable for the pathogenesis of diabetic complications call for time to reflect. This twenty-year journey focuses on the most relevant literature regarding the main sources of ROS generation in diabetes and their role in the pathogenesis of cell dysfunction and diabetic complications. To identify future research directions, this review discusses the evidence in favor and against oxidative stress as an initial event in the cellular biochemical abnormalities induced by hyperglycemia. It also explores possible alternative mechanisms, including carbonyl stress and the Warburg effect, linking glucose and lipid excess, mitochondrial dysfunction, and the activation of alternative pathways of glucose metabolism leading to vascular cell injury and inflammation. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Diabetes and Complications: From Biomarkers to Therapeutic Targets)
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Other

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15 pages, 903 KiB  
Systematic Review
Effects of Antioxidant in Adjunct with Periodontal Therapy in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
by Koji Mizutani, Prima Buranasin, Risako Mikami, Kohei Takeda, Daisuke Kido, Kazuki Watanabe, Shu Takemura, Keita Nakagawa, Hiromi Kominato, Natsumi Saito, Atsuhiko Hattori and Takanori Iwata
Antioxidants 2021, 10(8), 1304; https://doi.org/10.3390/antiox10081304 - 18 Aug 2021
Cited by 13 | Viewed by 4589
Abstract
This review investigated whether the adjunctive use of antioxidants with periodontal therapy improves periodontal parameters in patients with type 2 diabetes. A systematic and extensive literature search for randomized controlled trials (RCTs) conducted before April 2021 was performed on the PubMed, Cochrane Library, [...] Read more.
This review investigated whether the adjunctive use of antioxidants with periodontal therapy improves periodontal parameters in patients with type 2 diabetes. A systematic and extensive literature search for randomized controlled trials (RCTs) conducted before April 2021 was performed on the PubMed, Cochrane Library, and Web of Science databases. The risk of bias was assessed using the Cochrane risk-of-bias tool. A meta-analysis was performed to quantitatively evaluate the clinical outcomes following periodontal therapy. After independent screening of 137 initial records, nine records from eight RCTs were included. The risk-of-bias assessment revealed that all RCTs had methodological weaknesses regarding selective bias, although other risk factors for bias were not evident. This meta-analysis of two RCTs showed that periodontal pocket depths were significantly reduced in the groups treated with combined non-surgical periodontal therapy and melatonin than in those treated with non-surgical periodontal therapy alone. The present systematic review and meta-analysis suggest that the adjunctive use of melatonin, resveratrol, omega-3 fatty acids with cranberry juice, propolis, and aloe vera gel with periodontal therapy significantly improves periodontal disease parameters in patients with type 2 diabetes, and melatonin application combined with non-surgical periodontal therapy might significantly reduce periodontal pocket depth. However, there are still limited studies of melatonin in combination with non-surgical periodontal therapy in Type 2 diabetic patients, and more well-designed RCTs are required to be further investigated. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Diabetes and Complications: From Biomarkers to Therapeutic Targets)
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