Oxidative Stress, DNA Damage and Repair Pathways in Patients with Type 2 Diabetes Mellitus

Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM.Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, GGT, uric acid, total leukocyte/neutrophil count, and urinary 8-oxo-deoxyguanosine (u-8-oxodG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications.BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-oxodG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Age-dependent increase in u-8-oxodG suggests that aging process, rather than metabolic disturbances or diabetes per se plays a pivotal role in development of oxidative DNA-damage in T2DM. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

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DNA damage and repair in type 2 diabetes mellitus

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ◽

10.1016/j.mrfmmm.2004.05.011 ◽

2004 ◽

Vol 554 (1-2) ◽

pp. 297-304 ◽

Cited By ~ 123

Author(s):

Janusz Blasiak ◽

Michal Arabski ◽

Renata Krupa ◽

Katarzyna Wozniak ◽

Marek Zadrozny ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Damage ◽

Type 2 Diabetes Mellitus ◽

Dna Damage And Repair

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Parameters of oxidative stress, DNA damage and DNA repair in type 1 and type 2 diabetes mellitus

Archives of Physiology and Biochemistry ◽

10.3109/13813455.2010.551135 ◽

2011 ◽

Vol 117 (4) ◽

pp. 222-230 ◽

Cited By ~ 28

Author(s):

Lukáš Pácal ◽

Jana Varvařovská ◽

Zdeněk Rušavý ◽

Silva Lacigová ◽

Rudolf Štětina ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Damage ◽

Dna Repair ◽

Type 2 Diabetes Mellitus

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ASSESSMENT OF DNA STRAND BREAKS AND TOTAL ANTIOXIDANT STATUS IN TYPE 2 DIABETIC PATIENTS WITH AND WITHOUT COMPLICATIONS- A CASE-CONTROL STUDY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i4.17020 ◽

2017 ◽

Vol 10 (4) ◽

pp. 430

Author(s):

K Nithya ◽

Isabel W ◽

Angeline T ◽

Priscilla As ◽

Asirvatham Aj

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Damage ◽

Type 2 Diabetes Mellitus ◽

Antioxidant Status ◽

Total Antioxidant Status ◽

Diabetic Patients ◽

Total Antioxidant

Objective: To evaluate the total antioxidant status (TAS) and the extent of DNA strand breaks (damage) as a measure of oxidative stress biomarkers in Type 2 diabetic patients (with and without complications) and controls.Materials and Methods: Blood samples were collected from 200 patients with type 2 diabetes mellitus (n=100 with complications and n=100 without complications) and 100 healthy individuals. Oxidative DNA damage was evaluated using alkaline single cell gel electrophoresis (comet assay). Total antioxidant status was assessed by Ferric Reducing Ability of Plasma (FRAP) assay.Results: TAS was found to be significantly lower in type 2 diabetic patients (with and without complications) compared to controls (p< 0.001). Similarly, patients with complications of type 2 diabetes mellitus had significantly lower TAS when compared to diabetic patients (p= 0.007). DNA damage analysis showed that the extent of damage was high in patients with diabetes mellitus (with and without complications) compared to controls (p< 0.001). Fasting glucose and glycosylated haemoglobin level (HbA1c) was found to be significantly higherin diabetic patients than controls (p< 0.05). Correlation analysis showed that there is no association between age, duration, sugar level, HbA1c, TAS and DNA damage in patients with Type 2 diabetes mellitus.Conclusion: Alterations in TAS and the extent of DNA damage was observed in patients with complications of diabetes mellitus indicate that oxidative stress is more in patients with complications when compared to patients without complications and healthy individuals. Therefore, further DNA damage and onset of complications in Type 2 diabetes mellitus could be prevented by counteracting the oxidative stress by therapeutic interventions using appropriate antioxidants.Key words: Hyperglycemia, Oxidative stress, DNA damage, Total antioxidant status, Type 2 diabetes mellitus, Vascular complication

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910-P: Relationship between Continuous Glucose Monitoring Metrics and Oxidative Stress in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study

Diabetes ◽

10.2337/db20-910-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 910-P

Author(s):

YO KOHATA ◽

MAKOTO OHARA ◽

TOMOKI FUJIKAWA ◽

HIROE NAGAIKE ◽

HIDEKI KUSHIMA ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glucose Monitoring ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

And Oxidative Stress

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Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms22031059 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1059

Author(s):

Bodo C. Melnik

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Dopaminergic Neurons ◽

Vagal Nerve ◽

Β Cells ◽

Pancreatic Β Cells ◽

The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

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