Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
PLoS One
2016 Jan 01;119:e0162082. doi: 10.1371/journal.pone.0162082.
Show Gene links
Show Anatomy links
Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2.
Grindel A
,
Guggenberger B
,
Eichberger L
,
Pöppelmeyer C
,
Gschaider M
,
Tosevska A
,
Mare G
,
Briskey D
,
Brath H
,
Wagner KH
.
???displayArticle.abstract???
BACKGROUND: Diabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration.
METHODS: Female T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals.
RESULTS: No significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group.
CONCLUSION: BMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria.
???displayArticle.pubmedLink???
27598300
???displayArticle.pmcLink???PMC5012603 ???displayArticle.link???PLoS One
Fig 1. Fold changes of mRNA expression of DNA BER enzymes.T2DM patients with HbA1c>7.5% (n = 23) in relation to matched T2DM patients with HbA1c<7.5% (n = 23). For each pair, results were normalized to the HbA1c<7.5% expression. Matching was according to age, medication and smoking history. Significance was assumed at p<0.05 and tested with one-sample t-test against “1” or Wilcoxon test against “1” if normal distribution was not assumed. (a) Fold-changes presented as bar plots showing mean and standard deviation. (b) Distribution of fold changes. Each point represents a matching pair (n = 23).
Aebi,
Catalase in vitro.
1984,
Pubmed
Al-Salmani,
Simplified method for the collection, storage, and comet assay analysis of DNA damage in whole blood.
2011,
Pubmed
Algire,
Metformin reduces endogenous reactive oxygen species and associated DNA damage.
2012,
Pubmed
Aouacheri,
The investigation of the oxidative stress-related parameters in type 2 diabetes mellitus.
2015,
Pubmed
Azqueta,
A comparative performance test of standard, medium- and high-throughput comet assays.
2013,
Pubmed
Azqueta,
DNA oxidation: investigating its key role in environmental mutagenesis with the comet assay.
2009,
Pubmed
Azqueta,
Measurement of DNA base and nucleotide excision repair activities in mammalian cells and tissues using the comet assay--a methodological overview.
2013,
Pubmed
Benzie,
The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay.
1996,
Pubmed
Blasiak,
DNA damage and repair in type 2 diabetes mellitus.
2004,
Pubmed
Bondor,
Relationship of adiponectin to markers of oxidative stress in type 2 diabetic patients: influence of incipient diabetes-associated kidney disease.
2015,
Pubmed
Boon,
Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome.
2012,
Pubmed
Brenerman,
Base excision repair capacity in informing healthspan.
2014,
Pubmed
Briskey,
Optimized method for quantification of total F(2)-isoprostanes using gas chromatography-tandem mass spectrometry.
2014,
Pubmed
Brownlee,
Biochemistry and molecular cell biology of diabetic complications.
2001,
Pubmed
Calabrese,
Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes.
2012,
Pubmed
Caldecott,
An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III.
1994,
Pubmed
,
Xenbase
Choi,
Inter-relationships between DNA damage, ascorbic acid and glycaemic control in Type 2 diabetes mellitus.
2005,
Pubmed
D'Agostino,
General cardiovascular risk profile for use in primary care: the Framingham Heart Study.
2008,
Pubmed
Dinçer,
Assessment of DNA base oxidation and glutathione level in patients with type 2 diabetes.
2002,
Pubmed
Ellenberger,
Eukaryotic DNA ligases: structural and functional insights.
2008,
Pubmed
Fiorentino,
Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases.
2013,
Pubmed
Guariguata,
Global estimates of diabetes prevalence for 2013 and projections for 2035.
2014,
Pubmed
Gupta,
Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population.
2013,
Pubmed
Ha,
The association of specific metabolites of lipid metabolism with markers of oxidative stress, inflammation and arterial stiffness in men with newly diagnosed type 2 diabetes.
2012,
Pubmed
Hawkins,
Quantification of protein modification by oxidants.
2009,
Pubmed
Hissin,
A fluorometric method for determination of oxidized and reduced glutathione in tissues.
1976,
Pubmed
Hu,
Measurement of protein thiol groups and glutathione in plasma.
1994,
Pubmed
Ibarra-Costilla,
DNA damage evaluated by comet assay in Mexican patients with type 2 diabetes mellitus.
2010,
Pubmed
Kahn,
Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes.
2001,
Pubmed
Kahn,
Mechanisms linking obesity to insulin resistance and type 2 diabetes.
2006,
Pubmed
Kasuga,
Insulin resistance and pancreatic beta cell failure.
2006,
Pubmed
Koenig,
Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus.
1976,
Pubmed
Kumawat,
Antioxidant Enzymes and Lipid Peroxidation in Type 2 Diabetes Mellitus Patients with and without Nephropathy.
2013,
Pubmed
Lee,
Evidence for DNA damage as a biological link between diabetes and cancer.
2015,
Pubmed
Livak,
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
2001,
Pubmed
Manoel-Caetano,
Gene expression profiles displayed by peripheral blood mononuclear cells from patients with type 2 diabetes mellitus focusing on biological processes implicated on the pathogenesis of the disease.
2012,
Pubmed
Marin,
Oxidized HDL and LDL in adolescents with type 2 diabetes compared to normal weight and obese peers.
2015,
Pubmed
Marklund,
Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase.
1974,
Pubmed
Merecz,
Analysis of oxidative DNA damage and its repair in Polish patients with diabetes mellitus type 2: Role in pathogenesis of diabetic neuropathy.
2015,
Pubmed
Mittendorfer,
Insulin resistance: sex matters.
2005,
Pubmed
Moskalev,
The role of DNA damage and repair in aging through the prism of Koch-like criteria.
2013,
Pubmed
Müllner,
Impact of polyunsaturated vegetable oils on adiponectin levels, glycaemia and blood lipids in individuals with type 2 diabetes: a randomised, double-blind intervention study.
2014,
Pubmed
Müllner,
Vegetables and PUFA-rich plant oil reduce DNA strand breaks in individuals with type 2 diabetes.
2013,
Pubmed
Nakhjavani,
Serum oxidized-LDL is associated with diabetes duration independent of maintaining optimized levels of LDL-cholesterol.
2010,
Pubmed
Njajou,
Association between oxidized LDL, obesity and type 2 diabetes in a population-based cohort, the Health, Aging and Body Composition Study.
2009,
Pubmed
Preis,
Trends in all-cause and cardiovascular disease mortality among women and men with and without diabetes mellitus in the Framingham Heart Study, 1950 to 2005.
2009,
Pubmed
Prentki,
Islet beta cell failure in type 2 diabetes.
2006,
Pubmed
Ramel,
Plasma antioxidants and lipid oxidation after submaximal resistance exercise in men.
2004,
Pubmed
Schupp,
Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis.
2008,
Pubmed
Shah,
The role of DNA damage and repair in atherosclerosis: A review.
2015,
Pubmed
Stratton,
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.
2000,
Pubmed
Tupe,
Association of plasma proteins at multiple stages of glycation and antioxidant status with erythrocyte oxidative stress in patients with type 2 diabetes.
2014,
Pubmed
Vigneri,
Diabetes and cancer.
2009,
Pubmed
Xavier,
One-week intervention period led to improvements in glycemic control and reduction in DNA damage levels in patients with type 2 diabetes mellitus.
2014,
Pubmed
Xavier,
Assessment of DNA damage and mRNA/miRNA transcriptional expression profiles in hyperglycemic versus non-hyperglycemic patients with type 2 diabetes mellitus.
2015,
Pubmed
de Beer,
Does cancer risk increase with HbA1c, independent of diabetes?
2014,
Pubmed
de M Bandeira,
Oxidative stress as an underlying contributor in the development of chronic complications in diabetes mellitus.
2013,
Pubmed