Susceptibility of Glutathione--S-Transferase Polymorphism to CVD Development in Type 2 Diabetes Mellitus - A Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Santhi Priya Sobha ◽  
Kumar Ebenezar
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Metabolic Disorder ◽  
Vascular Complications ◽  
Clinical Importance ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Metabolic Conditions ◽  
Gst Polymorphism ◽  
Gene Status

Background: Metabolic disorder affects normal homeostasis and can lead to the development of diseases. Diabetes mellitus is the most common metabolic disorder, and a cluster of metabolic conditions can lead to cardiovascular disease (CVD) development. Diabetes mellitus and CVD are closely related, with oxidative stress, playing a major role in the pathophysiology. Glutathione-S-Transferases (GST) potentially play an important role by reducing oxidative stress and is found to be the underlying pathophysiology in the development of diabetes, cardiovascular diseases (CVD), etc. Objectives: In this review, the role of GST genetic variant in the development of diabetes mellitus, CVD and diabetic vascular complications has been focused. Results: Based on the literature, it is evident that the GST can act as an important biochemical tool providing significant evidence regarding oxidative stress predominant in the development of diseases. Analysis of GST gene status, particularly detection of GSTM1 and GSTT1 null mutations and GSTP1 polymorphism, have clinical importance. Conclusion: The analysis of GST polymorphism may help identify the people at risk and provide proper medical management. Genotyping of GST gene would be a helpful biomarker for early diagnosis of CVD development in DM and also in CVD cases. More studies focusing on the association of GST polymorphism with CVD development in diabetic patients will help us determine the pathophysiology better.

scholarly journals Oxidative lipid, protein, and DNA damage as oxidative stress markers in vascular complications of diabetes mellitus

2011 ◽  
Vol 34 (3) ◽  
pp. 163 ◽  
Author(s):  
Omur Tabak ◽  
Remise Gelisgen ◽  
Hayriye Erman ◽  
Fusun Erdenen ◽  
Cüneyt Muderrisoglu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Vascular Complications ◽  
Diabetic Group ◽  
Control Group ◽  
Diabetic Patients ◽  
Serum Samples ◽  
Type 2 Diabetic Patients

Purpose: The purpose of this study was to determine the effects of diabetic complications on oxidation of proteins, lipids, and DNA and to investigate the relationship between oxidative damage markers and clinical parameters. Methods: The study group consisted of 69 type 2 diabetic patients (20 patients without complication, 49 patients with complication) who attended internal medicine outpatient clinics of Istanbul Education and Research Hospital and 19 healthy control subjects. In serum samples of both diabetic patients and healthy subjects, 8-hydroxy-2’deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, Nε-(hexanoyl)lysine (HEL) and 15-F2t-iso-prostaglandin (15-F2t-IsoP). as products of lipooxidative damage, advanced oxidation protein products (AOPP), as markers of protein damage, and paraoxonase1 (PON1) as antioxidant were studied. Results: 15-F2t-IsoP (p < 0.005) and AOPP (p < 0.001) levels were significantly higher in diabetic group than control group while there were no significant differences in levels of 8-OHdG and HEL between the two groups. AOPP (p < 0.001) and 8-OHdG (p < 0.001) were significantly higher in diabetic group with complications compared to diabetic group without complications. Conclusions: Increased formation of free radicals and oxidative stress, under conditions of hyperglycaemia, is one of the probable causes for evolution of complications in diabetes mellitus. Our study supports the hypothesis that oxidant/antioxidant balance is disturbed in diabetic patients.

Relationship of Soluble RAGE and RAGE Ligands HMGB1 and EN-RAGE to Endothelial Dysfunction in Type 1 and Type 2 Diabetes Mellitus

2012 ◽  
Vol 120 (05) ◽  
pp. 277-281 ◽  
Author(s):  
J. Škrha Jr ◽  
M. Kalousová ◽  
J. Švarcová ◽  
A. Muravská ◽  
J. Kvasnička ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Advanced Glycation Endproducts ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Glycation Endproducts ◽  
Diabetic Vascular Complications ◽  
Soluble Rage

AbstractReceptor for advanced glycation endproducts (RAGE) plays the essential role in the pathogenesis of diabetic vascular complications. The aim of the study was to compare concentration of soluble RAGE and its ligands (EN-RAGE and HMGB1) with different biochemical parameters in Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus.Total number of 154 persons (45 T1DM, 68 T2DM, 41 controls) was examined and concentrations of sRAGE, EN-RAGE and HMGB1 were measured and compared to diabetes control, albuminuria, cell adhesion molecules and metalloproteinases (MMPs).Mean serum sRAGE concentration was higher in T1DM as compared to controls (1137±532 ng/l vs. 824±309 ng/l, p<0.01). Similarly, EN-RAGE was significantly higher in both diabetic groups (p<0.001) and HMGB1 concentrations were elevated in T2DM patients (p<0.01). Significant relationship was found between MMP9 and HMGB1 and EN-RAGE in diabetic patients. Inverse relationship was observed between MMP2 and MMP9 in both types of diabetic patients (r= − 0.602, p<0.002 and r= − 0.771, p<0.001). Significant positive correlation was found between sRAGE and ICAM-1, VCAM-1 or vWF (p<0.01 to p<0.001).We conclude that serum sRAGE and RAGE ligands concentrations reflect endothelial dysfunction developing in diabetes.

scholarly journals S-glutathionylation: relevance in diabetes and potential role as a biomarker

2013 ◽  
Vol 394 (10) ◽  
pp. 1263-1280 ◽  
Author(s):  
Francisco J. Sánchez-Gómez ◽  
Cristina Espinosa-Díez ◽  
Megha Dubey ◽  
Madhu Dikshit ◽  
Santiago Lamas
Keyword(s):  
Oxidative Stress ◽  
Vascular Complications ◽  
Redox Balance ◽  
Diabetic Patients ◽  
Sulfenic Acid ◽  
Diabetic Vascular Complications ◽  
Main Regulator ◽  
Species Production

Abstract Glutathione is considered the main regulator of redox balance in the cellular milieu due to its capacity for detoxifying deleterious molecules. The oxidative stress induced as a result of a variety of stimuli promotes protein oxidation, usually at cysteine residues, leading to changes in their activity. Mild oxidative stress, which may take place in physiological conditions, induces the reversible oxidation of cysteines to sulfenic acid form, while pathological conditions are associated with higher rates of reactive oxygen species production, inducing the irreversible oxidation of cysteines. Among these, neurodegenerative disorders, cardiovascular diseases and diabetes have been proposed to be pathogenetically linked to this state. In diabetes-associated vascular complications, lower levels of glutathione and increased oxidative stress have been reported. S-glutathionylation has been proposed as a posttranslational modification able to protect proteins from over-oxidizing environments. S-glutathionylation has been identified in proteins involved in diabetic models both in vitro and in vivo. In all of them, S-glutathionylation represents a mechanism that regulates the response to diabetic conditions, and has been described to occur in erythrocytes and neutrophils from diabetic patients. However, additional studies are necessary to discern whether this modification represents a biomarker for the early onset of diabetic vascular complications.

scholarly journals Endothelial Dysfunction in Diabetes Mellitus: Possible Involvement of Endoplasmic Reticulum Stress?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Basma Basha ◽  
Samson Mathews Samuel ◽  
Chris R. Triggle ◽  
Hong Ding
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Clinical Trials ◽  
Endoplasmic Reticulum ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Therapeutic Agents ◽  
Recent Past

The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications have been correlated to the hyperglycemia-induced oxidative stress and associated endothelial dysfunction. Although antioxidants may be considered as effective therapeutic agents to relieve oxidative stress and protect the endothelium, recent clinical trials involving these agents have shown limited therapeutic efficacy in this regard. In the recent past experimental evidence suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be an important contributor to diabetes-related vascular complications. The current paper contemplates the possibility of the involvement of ER stress in endothelial dysfunction and diabetes-associated vascular complications.

scholarly journals The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy

2008 ◽  
Vol 27 (3) ◽  
pp. 376-382 ◽  
Author(s):  
Tatjana Cvetković ◽  
Predrag Vlahović ◽  
Vidosava đorđević ◽  
Lilika Zvezdanović ◽  
Dušica Pavlović ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Urine Concentration ◽  
Control Group ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Urinary Markers ◽  
Stress Markers

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-β-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p<0.001 and P<0.05). The urine concentration of RCD shows similar results with a significant elevation in the groups with DMT2-MAA and DMT1-MIA, compared to the DMT2-MIA (p<0.001) and control group (p<0.001). Activities of NAG, APN and DPPIV were significantly higher in the urine of DMT2-MAA, compared to the control (p<0.01). The activity of PC-1 was slightly increased in that group, but not significantly. In conclusion, the level of oxidative stress markers and activities of brush border ectoenzymes in the urine may be a useful non-invasive and easily repeatable test in DN.

scholarly journals To study levels of serum fibrinogen in type 2 diabetes mellitus and its association with diabetic microvascular complications

2017 ◽  
Vol 4 (1) ◽  
pp. 10
Author(s):  
Gurinder Mohan ◽  
Ranjeet Kaur ◽  
Aakash Aggarwal ◽  
Parminder Singh
Keyword(s):  
Diabetes Mellitus ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
High Serum ◽  
Diabetic Patients ◽  
Coagulation Disorder ◽  
Urine Albumin ◽  
Group A ◽  
Diabetic Microvascular Complications ◽  
Group B

Background: Diabetes mellitus is a hypercoagulable state associated with atherosclerosis leading to development of vascular complications, including microvascular complications.Methods: In our study a total of 60 diabetic patients with duration of diabetes more than 5 years, attending the OPD/ indoor of SGRDIMSR, Amritsar, Punjaqqb, India were included. They were divided in two groups, group A of 30 patients including diabetics with any of the three microvascular complications (diabetic nephropathy, diabetic retinopathy and diabetic neuropathy) and group B of 30 patients including diabetics without any microvascular complication. Group C comprised of 30 age and sex matched non-diabetic subjects who served as controls. Subjects with liver cirrhosis, malignancy or coagulation disorder were excluded. After taking the consent, detailed history taking and detailed physical examination and relevant investigations were done. The serum fibrinogen (hemostasis marker), HBA1C and UACR (urine albumin creatinine ratio) along with routine investigations were measured.Results: It was observed that serum fibrinogen levels were significantly higher in diabetic patients (266.16±54.73 mg/dl) as compared to non-diabetic controls (174.66±18.32 mg/dl); p <0.001.Further, serum fibrinogen levels were found to be significantly higher in diabetic patients with microvascular complications (293.43±51.09 mg/dl) as compared to those without microvascular complications (238.90±44.12); p<0.001.Conclusions: Significantly high serum fibrinogen level was found in diabetic patients as compared to controls and was in positive correlation with development of microvascular complications.

scholarly journals Glycaemic Regulation with Zinc Combination in Type 2 Diabetes Mellitus

2021 ◽  
pp. 33-37
Author(s):  
Gangaram Bhadarge ◽  
Pratibha Dawande ◽  
Nandkishor Bankar ◽  
Raunak Kotecha
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Zn Deficiency ◽  
Diabetic Patients ◽  
Chronic Hyperglycemia ◽  
Low Levels

Introduction: Zn supplementation improved glutathione peroxidase enzyme activity and decreased malondialdehyde and nitric oxide levels in diabetic rats, revealing Zn's defensive effect against oxidative stress in type 2 diabetes. The investigators have discovered that consuming Zn increased liver function and protected pancreatic tissue from damage caused by diabetes. Since Zn also prevents chronic hyperglycemia, it helps to minimize oxidative stress caused by type 2 diabetes. Diabetes mellitus (DM) is a global health problem that affects more than 3 million people worldwide (16% of population). Chronic hyperglycemia causes oxidative stress in diabetic patients by the development of free radicals (oxidants) and lowering the antioxidant protection mechanism. Aim: Glycaemic Regulation with Zinc Combination in Type 2 Diabetes Mellitus. Materials and Methods: Faculty of Medicine and Diabetic Opd, Datta Meghe Mediсаl Соllege and Shаlinitаi Meghe Hоsрitаl аnd Reseаrсh Сenter, Nаgрur in соllаbоrаtion with Dаttа Meghe Institute оf Mediсаl Sсienсes Deemed to be University, Sаwаngi, Wаrdhа, Mаhаrаshtrа. Results: The mean Zn level was 12.213±2.342in all participants and 9.121±1.782 in the control group, whereas it was significantly low (9.121±1.782) in the diabetic group, and there was statistically significant difference in Zn levels between the controls and the diabetic group (P < 0.001).FBS, HbA1C, serum Zinc mean effects between control and patients showed statistically significant differences in type 2 diabetes mellitus (P <0.0001). Conclusion: Our findings show that people with diabetes have lower levels of Zn than healthy people. The cause and effect of the association between very low levels of Zn and the progression of diabetes, or diabetes that causes Zn deficiency, is still unknown. Low levels of Zn are associated with poor glycemic control, and poor glycemic control is a good indication of Zn deficiency, as there was a negative association between serum Zn and FBS and HBA1C. If diabetic patients have low glycemic regulation, a long history of diabetes, obesity, or are over the age of 50, we look to assess their levels in Zn so that Zn alternative treatment can begin to release oxidative stress in this high-risk group.

scholarly journals Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yanan Sun ◽  
Cao Ma ◽  
Hui Sun ◽  
Huan Wang ◽  
Wei Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Impaired Insulin ◽  
The Brain

As a chronic metabolic disease, diabetes mellitus (DM) is broadly characterized by elevated levels of blood glucose. Novel epidemiological studies demonstrate that some diabetic patients have an increased risk of developing dementia compared with healthy individuals. Alzheimer’s disease (AD) is the most frequent cause of dementia and leads to major progressive deficits in memory and cognitive function. Multiple studies have identified an increased risk for AD in some diabetic populations, but it is still unclear which diabetic patients will develop dementia and which biological characteristics can predict cognitive decline. Although few mechanistic metabolic studies have shown clear pathophysiological links between DM and AD, there are several plausible ways this may occur. Since AD has many characteristics in common with impaired insulin signaling pathways, AD can be regarded as a metabolic disease. We conclude from the published literature that the body’s diabetic status under certain circumstances such as metabolic abnormalities can increase the incidence of AD by affecting glucose transport to the brain and reducing glucose metabolism. Furthermore, due to its plentiful lipid content and high energy requirement, the brain’s metabolism places great demands on mitochondria. Thus, the brain may be more susceptible to oxidative damage than the rest of the body. Emerging evidence suggests that both oxidative stress and mitochondrial dysfunction are related to amyloid-β (Aβ) pathology. Protein changes in the unfolded protein response or endoplasmic reticulum stress can regulate Aβ production and are closely associated with tau protein pathology. Altogether, metabolic disorders including glucose/lipid metabolism, oxidative stress, mitochondrial dysfunction, and protein changes caused by DM are associated with an impaired insulin signal pathway. These metabolic factors could increase the prevalence of AD in diabetic patients via the promotion of Aβ pathology.

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