URINARY MARKERS OF OXIDATIVE DNA DAMAGE IN TYPE 1 DIABETIC CHILDREN: RELATION TO MICROVASCULAR COMPLICATIONS

  • Maged A. El Wakeel Associate professor of Child Health, National Research Centre, Cairo, Egypt
  • Mohamed Abou-el-asrar Professor of Pediatrics, Faculty of Medicine, Ain-Shams University, Egypt
  • Ghada Mahmoud El-kassas Associate professor of Child Health, National Research Centre, Cairo, Egypt
  • Mona A Elabd Researcher of Child Health, National Research Centre, Cairo, Egypt
  • Dina Abu Zeid Researcher of Child Health, National Research Centre, Cairo, Egypt
  • Rania N Sabry Associate professor of Child Health, National Research Centre, Cairo, Egypt
  • Eman Awadallah Researcher of Clinical and Chemical Pathology department, National Research Centre, Cairo, Egypt

Abstract

 

 Objective: Type 1 diabetes mellitus (T1DM) is a widespread metabolic disease, which frequently carries with it a significant impact on human health. Oxidative damage and tissue inflammation have been claimed to be a typical pathogenic component for the progression of diabetic complications. We aim in this study to explore the relation of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) (as a marker of nucleic acid oxidation) to microvascular complications in T1DM.

Methods: A case–control study, enrolling 45 T1DM children and an equivalent number of healthy subjects, was performed. Full clinical examination and anthropometric measurement were performed to all subjects. Urinary assessment for 8-oxodG and albumin was done in addition to blood sampling for lipid profile and glycated Hb (HbA1c) assay. Complete ocular examination for assessment of diabetic retinopathy (DR) was also done.

Results: Levels of urinary 8-oxodG, serum cholesterol, triglycerides, and low-density lipoprotein in cases were significantly higher than non-diabetics; these levels were likewise higher in uncontrolled T1DM patients in comparison with well-controlled T1DM subjects. Urinary 8-oxodG and HbA1c were significantly higher in diabetic patients with albuminuria and DR compared to patients without complications. Significant positive correlation was found between 8-oxodG with HbA1c (r=0.8, p<0.01), diastolic blood pressure (DBP) (r=0.4, p=0.02), and cholesterol (r=0.4, p=0.05).

Conclusion: Urinary 8-oxodG was found to be a reliable marker for assessing oxidative DNA damage in T1DM and can be used in the determination of microvascular complications related to diabetes.

Keywords: Urinary 8-oxo-7, 8-dihydro-2′-deoxyguanosine, Type1 diabetes, DNA oxidation, Microvascular complications.

References

1. Soltesz G, Patterson C, Dahlquist G. Diabetes in the Young: A Global Perspective IDF Diabetes Atlas. 4th ed. Pecs, Hungary: Department of Pediatrics; 2009. p. 1-36.
2. Scaramuzza AE, Redaelli F, Giani E, Macedoni M, Giudici V, Gazzarri A, et al. Adolescents and young adults with Type 1 diabetes display a high prevalence of endothelial dysfunction. Acta Paediatr 2015;104(2):192-7.
3. Prabhakar PK. Pathophysiology of secondary complications of diabetes mellitus. Asian J Pharm Clin Res 2016;9(1):32-6.
4. Madan R, Gupt B, Saluja S, Kansra UC, Tripathi BK, Guliani BP. Coagulation profile in diabetes and its association with diabetic microvascular complications. J Assoc Physicians India 2010;58:481-4.
5. Calcutt NA, Cooper ME, Kern TS, Schmidt AM. Therapies for hyperglycaemia-induced diabetic complications: From animal models to clinical trials. Nat Rev Drug Discov 2009;8(5):417-29.
6. Altincik A, Tuglu B, Demir K, Çatli G, Abaci A, Böber E. Relationship between oxidative stress and blood glucose fluctuations evaluated with daily glucose monitoring in children with Type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2016;29(4):435-9.
7. Broedbaek K, Siersma V, Henriksen T, Weimann A, Petersen M, Andersen JT, et al. Urinary markers of nucleic acid oxidation and cancer in Type 2 diabetes. Redox Biol 2015;4:34-9.
8. Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta 2014;1840(9):2709-29.
9. Tatsch E, Bochi GV, Piva SJ, De Carvalho JA, Kober H, Torbitz VD, et al. Association between DNA strand breakage and oxidative, inflammatory and endothelial biomarkers in Type 2 diabetes. Mutat Res 2012;732(1-2):16-20.
10. Lohman TG, Roche AF, Martorell R. Human variation in anthropometric dimensions. In: Anthropometric Standardization Reference Manual. Champaign, IL: Human Kinetics Publishers; 1988. p. 86-107.
11. Group WMGRS. WHO child growth standards: Length/height-forage, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. In: WHO Press, editors. WHO Child Growth Standards. Geneva, Switzerland: World Health Organization; 2006. p. 312. Available from: http://www.who.int/childgrowth/standards/Technical_report.pdf. [Last accessed on 2011 Aug 11].
12. Wühl E, Witte K, Soergel M, Mehls O, Schaefer F; German Working Group on Pediatric Hypertension. Distribution of 24-h ambulatory blood pressure in children: Normalized reference values and role of body dimensions. J Hypertens 2002;20(10):1995-2007.
13. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18(6):499-502.
14. Pagel J. Biographisches Lexikon hervorragender Ärzte des Neunzehnten Jahrhunderts. Berlin: Urban & Schwarzenberg; 2012. p. 814. Available from: https://archive.org/details/biographischesl01pagegoog. [Last retrieved on 2012 Oct 19].
15. Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003;110(9):1677-82.
16. Krauss RM. Lipids and lipoproteins in patients with Type 2 diabetes. Diabetes Care 2004;27(6):1496-504.
17. Broedbaek K, Weimann A, Stovgaard ES, Poulsen HE. Urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine as a biomarker in Type 2 diabetes. Free Radic Biol Med 2011;51(8):1473-9.
18. El-Gindi HD, Hassanin AI, Mostafa NO, El-Kassas GM, El Wakeel MA, El-Batal WH, et al. Oxidative DNA damage in β-thalassemic children. Med Res J 2015;14(2):41-6.
19. Dong QY, Cui Y, Chen L, Song J, Sun L. Urinary 8-hydroxydeoxyguanosine levels in diabetic retinopathy patients. Eur J Ophthalmol 2008;18(1):94-8.
20. Al-Aubaidy HA, Jelinek HF. Oxidative DNA damage and obesity in Type 2 diabetes mellitus. Eur J Endocrinol 2011;164(6):899-904.
21. Xu GW, Yao QH, Weng QF, Su BL, Zhang X, Xiong JH. Study of urinary 8-hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in diabetic nephropathy patients. J Pharm Biomed Anal 2004;36(1):101-4.
22. Wu LL, Chiou CC, Chang PY, Wu JT. Urinary 8-OHdG: A marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta 2004;339(1-2):1-9.
23. Poulsen HE, Nadal LL, Broedbaek K, Nielsen PE, Weimann A. Detection and interpretation of 8-oxodG and 8-oxoGua in urine, plasma and cerebrospinal fluid. Biochim Biophys Acta 2014;1840(2):801-8.
24. El Wakeel MA, El-Kassas GM, Amer AF, Elbatal WH, Sabry RN, EL-Ghaffar Mohammed NA. E-selectin and vascular complications in children with Type 1 diabetes mellitus. Med Res J 2014;13(1):27-32.
25. Soubra L, Nureddin H, Omar AG, Saleh M. Factors associated with hypertension prevalence and control among lebanese Type 2 diabetic patients. Int J Pharm Pharm Sci 2016;8(10):153-9.
26. Nayak B, Bhaktha G. Inconsistent lipid profiles exhibited among the diabetic Asian Indians of India and trinidad - A comparative study. Int J Pharm Pharm Sci 2016;8(12):60-3.
27. Hinokio Y, Suzuki S, Hirai M, Suzuki C, Suzuki M, Toyota T. Urinary excretion of 8-oxo-7, 8-dihydro-2’-deoxyguanosine as a predictor of the development of diabetic nephropathy. Diabetologia 2002;45(6):877-82.
28. Nishikawa T, Sasahara T, Kiritoshi S, Sonoda K, Senokuchi T, Matsuo T, et al. Evaluation of urinary 8-hydroxydeoxy-guanosine as a novel biomarker of macrovascular complications in Type 2 diabetes. Diabetes Care 2003;26(5):1507-12.
29. Shimoike T, Inoguchi T, Umeda F, Nawata H, Kawano K, Ochi H. The meaning of serum levels of advanced glycosylation end products in diabetic nephropathy. Metabolism 2000;49(8):1030-5.
30. Kanauchi M, Nishioka H, Hashimoto T. Oxidative DNA damage and tubulointerstitial injury in diabetic nephropathy. Nephron 2002;91(2):327-9.
31. Tatsch E, De Carvalho JA, Hausen BS, Bollick YS, Torbitz VD, Duarte T, et al. Oxidative DNA damage is associated with inflammatory response, insulin resistance and microvascular complications in Type 2 diabetes. Mutat Res 2015;782:17-22.
32. Liu X, Gan W, Zou Y, Yang B, Su Z, Deng J, et al. Elevated levels of urinary markers of oxidative DNA and RNA damage in Type 2 diabetes with complications. Oxid Med Cell Longev 2016;2016:4323198. 33. Erusalimsky JD. Vascular endothelial senescence: From mechanisms to pathophysiology. J Appl Physiol 2009;106(1):326-32.
34. Nithya K, Isabel W, Angeline T, Priscilla AS, Asirvatham AJ. Assessment of DNA strand breaks and total antioxidant status in patients with Type 2 diabetes with and without complications: A case-control study. Asian J Pharm Clin Res 2017;10(4):430-4.
35. Cooke MS, Olinski R, Loft S; European Standards Committee on Urinary (DNA) Lesion Analysis. Measurement and meaning of oxidatively modified DNA lesions in urine. Cancer Epidemiol Biomarkers Prev 2008;17(1):3-14.
36. Brodsky SV, Gealekman O, Chen J, Zhang F, Togashi N, Crabtree M, et al. Prevention and reversal of premature endothelial cell senescence and vasculopathy in obesity-induced diabetes by ebselen. Circ Res 2004;94(3):377-84.
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El Wakeel, M. A., M. Abou-el-asrar, G. M. El-kassas, M. A. Elabd, D. Abu Zeid, R. N. Sabry, and E. Awadallah. “URINARY MARKERS OF OXIDATIVE DNA DAMAGE IN TYPE 1 DIABETIC CHILDREN: RELATION TO MICROVASCULAR COMPLICATIONS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 10, Sept. 2017, pp. 318-22, doi:10.22159/ajpcr.2017.v10i10.18930.
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