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Association between urinary 8-OHdG and pulse wave velocity in hypertensive patients with type 2 diabetes mellitus

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Singapore Med J2014; 55(4): 202-208; http://dx.doi.org/10.11622/smedj.2014053
Association between urinary 8-OHdG and pulse wave velocity in hypertensive patients with type 2 diabetes mellitus

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Kotani K, Yamada T
Correspondence: Dr Kazuhiko Kotani, kazukotani@jichi.ac.jp

ABSTRACT
INTRODUCTION Oxidative stress, assessed using 8-hydroxy-2’-deoxyguanosine (8-OHdG), can be associated with arterial stiffness in patients with type 2 diabetes mellitus (T2DM) and/or hypertension (HT). We investigated the correlation between urinary 8-OHdG and pulse wave velocity (PWV) in hypertensive and non-hypertensive T2DM patients with fair glycaemic control to determine the clinical significance of HT as a comorbidity in the diabetic state.
METHODS Clinical data, including traditional cardiovascular risk factors, diabetic complications, prescribed agents, urinary 8-OHdG level and brachial-ankle PWV, was collected from T2DM patients with and without HT. 
RESULTS There were 76 patients (45 men, 31 women; mean age 61 years; mean haemoglobin A1c level 6.5%) in the study cohort. T2DM patients with HT had significantly higher mean PWV than patients without HT (1,597 cm/s vs 1,442 cm/s; p < 0.05). Patients with HT showed no significant difference in 8-OHdG levels relative to those without HT (median 7.9 ng/mg creatinine vs 8.8 ng/mg creatinine; p > 0.05). Simple linear correlation and stepwise multiple linear regression analyses revealed that 8-OHdG levels correlated independently, significantly and positively with PWV among T2DM patients with HT (r = 0.33, p < 0.05; β= 0.23, p < 0.05). No significant correlation was observed between 8-OHdG levels and PWV among T2DM patients without HT.
CONCLUSION In the hypertensive state, oxidative stress can be responsible for the development of arterial stiffness, even in patients with fairly well controlled T2DM. Oxidative stress management may be necessary for the prevention of cardiovascular disease in this population.

Keywords: arterial stiffness, atherosclerosis, DNA damage, oxidative stress, pulse wave velocity
Singapore Med J2014; 55(4): 202-208; http://dx.doi.org/10.11622/smedj.2014053

http://smj.org.sg/sites/default/files/5504/5504a3.pdf

REFERENCES

1. Sheu WH, Rosman A, Mithal A, et al. Addressing the burden of type 2 diabetes and cardiovascular disease through the management of postprandial hyperglycaemia: an Asian-Pacific perspective and expert recommendations. Diabetes Res Clin Pract 2011; 92:312-21.
http://dx.doi.org/10.1016/j.diabres.2011.04.019
 
2. Hu FB. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care 2011; 34:1249-57.
http://dx.doi.org/10.2337/dc11-0442
 
3. Chung N, Baek S, Chen MF, et al. Expert recommendations on the challenges of hypertension in Asia. Int J Clin Pract 2008; 62:1306-12.
http://dx.doi.org/10.1111/j.1742-1241.2008.01838.x
 
4. Nishikawa T, Sasahara T, Kiritoshi S, et al. Evaluation of urinary 8-hydroxydeoxy-guanosine as a novel biomarker of macrovascular complications in type 2 diabetes. Diabetes Care 2003; 26:1507-12.
http://dx.doi.org/10.2337/diacare.26.5.1507
 
5. Stehouwer CD, Henry RM, Ferreira I. Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia 2008; 51:527-39.
http://dx.doi.org/10.1007/s00125-007-0918-3
 
6. Montezano AC, Touyz RM. Oxidative stress, Noxs, and hypertension: experimental evidence and clinical controversies. Ann Med 2012; 44 Suppl 1:S2-16.
http://dx.doi.org/10.3109/07853890.2011.653393
 
7. Piconi L, Quagliaro L, Ceriello A. Oxidative stress in diabetes. Clin Chem Lab Med 2003; 41:1144-9.
http://dx.doi.org/10.1515/CCLM.2003.177
 
8. 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; 339:1-9.
http://dx.doi.org/10.1016/j.cccn.2003.09.010
 
9. Negishi H, Njelekela M, Ikeda K, et al. Assessment of in vivo oxidative stress in hypertensive rats and hypertensive subjects in Tanzania, Africa. Hypertens Res 2000; 23:285-9.
http://dx.doi.org/10.1291/hypres.23.285
 
10. Xu S, Touyz RM. Reactive oxygen species and vascular remodelling in hypertension: still alive. Can J Cardiol 2006; 22:947-51.
http://dx.doi.org/10.1016/S0828-282X(06)70314-2
 
11. Leinonen J, Lehtimäki T, Toyokuni S, et al. New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent DM. FEBS Lett 1997; 417:150-2.
http://dx.doi.org/10.1016/S0014-5793(97)01273-8
 
12. Kanauchi M, Nishioka H, Hashimoto T. Oxidative DNA damage and tubulointerstitial injury in diabetic nephropathy. Nephron 2002; 91:327-9.
http://dx.doi.org/10.1159/000058412
 
13. Espinosa O, Jiménez-Almazán J, Chaves FJ, et al. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), a reliable oxidative stress marker in hypertension. Free Radic Res 2007; 41:546-54.
http://dx.doi.org/10.1080/10715760601164050
 
14. Roselló-Lletí E, de Burgos FG, Morillas P, et al. Impact of cardiovascular risk factors and inflammatory status on urinary 8-OHdG in essential hypertension. Am J Hypertens 2012; 25:236-42.
http://dx.doi.org/10.1038/ajh.2011.202
 
15. Nagayama D, Saiki A, Endo K, et al. Improvement of cardio-ankle vascular index by glimepiride in type 2 diabetic patients. Int J Clin Pract 2010; 64:1796 - 801.
http://dx.doi.org/10.1111/j.1742-1241.2010.02399.x
 
16. Miyashita Y, Saiki A, Endo K, et al. Effects of olmesartan, an angiotensin II receptor blocker, and amlodipine, a calcium channel blocker, on CardioAnkle Vascular Index (CAVI) in type 2 diabetic patients with hypertension. J Atheroscler Thromb 2009; 16:621-6.
http://dx.doi.org/10.5551/jat.497
 
17. Li CH, Wu JS, Yang YC, et al. Increased arterial stiffness in subjects with impaired glucose tolerance and newly diagnosed diabetes but not isolated impaired fasting glucose. J Clin Endocrinol Metab 2012; 97:E658-62.
http://dx.doi.org/10.1210/jc.2011-2595
 
18. Barengo NC, Tuomilehto JO. Blood pressure treatment target in patients with diabetes mellitus–current evidence. Ann Med 2012; 44 Suppl 1:S36-42.
http://dx.doi.org/10.3109/07853890.2012.679961
 
19. Masugata H, Senda S, Murao K, et al. Association between urinary 8-hydroxydeoxyguanosine, an indicator of oxidative stress, and the cardioankle vascular index in hypertensive patients. J Atheroscler Thromb 2012; 19:747-55.
 
20. Yamashina A, Tomiyama H, Takeda K, et al. Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertens Res 2002; 25:359-64.
http://dx.doi.org/10.1291/hypres.25.359
 
21. Oomichi T, Emoto M, Tabata T, et al. Impact of glycemic control on survival of diabetic patients on chronic regular hemodialysis: a 7-year observational study. Diabetes Care 2006; 29:1496-500.
http://dx.doi.org/10.2337/dc05-1887
 
22. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42:1206-52.
http://dx.doi.org/10.1161/01.HYP.0000107251.49515.c2
 
23. Imai E, Horio M, Nitta K, et al. Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol 2007; 11:41-50.
http://dx.doi.org/10.1007/s10157-006-0453-4
 
24. Toyokuni S, Tanaka T, Hattori Y, et al. Quantitative immunohistochemical determination of 8-hydroxy-2'-deoxyguanosine by a monoclonal antibody N45.1: its application to ferric nitrilotriacetate-induced renal carcinogenesis model. Lab Invest 1997; 76:365-74.
 
25. Yoshida R, Ogawa Y, Kasai H. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine values measured by an ELISA correlated well with measurements by high-performance liquid chromatography with electrochemical detection. Cancer Epidemiol Biomarkers Prev 2002; 11:1076-81.
 
26. Rossi MC, Nicolucci A, Pellegrini F, et al. Identifying patients with type 2 diabetes at high risk of microalbuminuria: results of the DEMAND (Developing Education on Microalbuminuria for Awareness of reNal and cardiovascular risk in Diabetes) Study. Nephrol Dial Transplant 2008; 23:1278 - 84.
http://dx.doi.org/10.1093/ndt/gfm798
 
27. Wilkinson CP, Ferris FL 3rd, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003; 110:1677-82.
http://dx.doi.org/10.1016/S0161-6420(03)00475-5
 
28. Thompson HJ, Heimendinger J, Haegele A, et al. Effect of increased vegetable and fruit consumption on markers of oxidative cellular damage. Carcinogenesis 1999; 20:2261-6.
http://dx.doi.org/10.1093/carcin/20.12.2261
 
29. Miquel J. Can antioxidant diet supplementation protect against age-related mitochondrial damage? Ann N Y Acad Sci 2002; 959:508-16.
http://dx.doi.org/10.1111/j.1749-6632.2002.tb02120.x
 
30. Nojima H, Watanabe H, Yamane K, et al. Effect of aerobic exercise training on oxidative stress in patients with type 2 diabetes mellitus. Metabolism 2008; 57:170-6.
http://dx.doi.org/10.1016/j.metabol.2007.08.021
 
31. Ozkanlar S, Akcay F. Antioxidant vitamins in atherosclerosis - animal experiments and clinical studies. Adv Clin Exp Med 2012; 21:115-23.
 
32. Kals J, Kampus P, Kals M, et al. Impact of oxidative stress on arterial elasticity in patients with atherosclerosis. Am J Hypertens 2006; 19:902-8.
http://dx.doi.org/10.1016/j.amjhyper.2006.02.003
 
33. Kals J, Kampus P, Kals M, et al. Inflammation and oxidative stress are associated differently with endothelial function and arterial stiffness in healthy subjects and in patients with atherosclerosis. Scand J Clin Lab Invest 2008; 68:594-601.
http://dx.doi.org/10.1080/00365510801930626
 
34. Ha CY, Kim JY, Paik JK, et al. 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. Clin Endocrinol (Oxf) 2012; 76:674-82.
http://dx.doi.org/10.1111/j.1365-2265.2011.04244.x
 
35. Dalfino G, Simone S, Porreca S, et al. Bone morphogenetic protein-2 may represent the molecular link between oxidative stress and vascular stiffness in chronic kidney disease. Atherosclerosis 2010; 211:418-23.
http://dx.doi.org/10.1016/j.atherosclerosis.2010.04.023
 
36. Kato M, Iida M, Goto Y, Kondo T, Yajima I. Sunlight exposure-mediated DNA damage in young adults. Cancer Epidemiol Biomarkers Prev 2011; 20:1622-8.
http://dx.doi.org/10.1158/1055-9965.EPI-11-0228
 
37. Abdilla N, Tormo MC, Fabia MJ, et al. Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension. J Hum Hypertens 2007; 21:68-75.
http://dx.doi.org/10.1038/sj.jhh.1002105
 
38. Martinet W, Knaapen MW, De Meyer GR, Herman AG, Kockx MM. Elevated levels of oxidative DNA damage and DNA repair enzymes in human atherosclerotic plaques. Circulation 2002; 106:927-32.
http://dx.doi.org/10.1161/01.CIR.0000026393.47805.21
 
39. Mazzone T, Chait A, Plutzky J. Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 2008; 371:1800-9.
http://dx.doi.org/10.1016/S0140-6736(08)60768-0
 
40. Ogawa S, Mori T, Nako K, Ito S. Combination therapy with renin-angiotensin system inhibitors and the calcium channel blocker azelnidipine decreases plasma inflammatory markers and urinary oxidative stress markers in patients with diabetic nephropathy. Hypertens Res 2008; 31:1147-55.
http://dx.doi.org/10.1291/hypres.31.1147
 
41. Nordstrand N, Gjevestad E, Dinh KN, et al. The relationship between various measures of obesity and arterial stiffness in morbidly obese patients. BMC Cardiovasc Disord 2011; 11:7.
http://dx.doi.org/10.1186/1471-2261-11-7
 
42. Lim S, Choi HJ, Shin H, et al. Subclinical atherosclerosis in a communitybased elderly cohort: the Korean Longitudinal Study on Health and Aging. Int J Cardiol 2012; 155:126-33.
http://dx.doi.org/10.1016/j.ijcard.2011.05.054
 
43. Tomita H, Kawamoto R, Tabara Y, Miki T, Kohara K. Blood pressure is the main determinant of the reflection wave in patients with type 2 diabetes. Hypertens Res 2008; 31:493-9.
http://dx.doi.org/10.1291/hypres.31.493
 
44. Xu L, Jiang CQ, Lam TH, et al. Brachial-ankle pulse wave velocity and cardiovascular risk factors in the non-diabetic and newly diagnosed diabetic Chinese: Guangzhou Biobank Cohort Study-CVD. Diabetes Metab Res Rev 2010; 26:133-9.
http://dx.doi.org/10.1002/dmrr.1059
 
45. Kim WJ, Park CY, Park SE, et al. The association between regional arterial stiffness and diabetic retinopathy in type 2 diabetes. Atherosclerosis 2012; 225:237- 41.
http://dx.doi.org/10.1016/j.atherosclerosis.2012.08.034
 
46. Nakagawa N, Takahashi F, Chinda J, et al. A newly estimated glomerular filtration rate is independently associated with arterial stiffness in Japanese patients. Hypertens Res 2008; 31:193-201.
http://dx.doi.org/10.1291/hypres.31.193
 
47. Maple-Brown LJ, Piers LS, O'Rourke MF, Celermajer DS, O'Dea K. Central obesity is associated with reduced peripheral wave reflection in Indigenous Australians irrespective of diabetes status. J Hypertens 2005; 23:1403-7.
http://dx.doi.org/10.1097/01.hjh.0000173524.80802.5a
 
48. Budimir D, Jeroncic A, Gunjaca G, et al. Sex-specific association of anthropometric measures of body composition with arterial stiffness in a healthy population. Med Sci Monit 2012; 18:CR65-71.
http://dx.doi.org/10.12659/MSM.882457
 
49. Huh JY, Son DJ, Lee Y, et al. 8-Hydroxy-2-deoxyguanosine prevents plaque formation and inhibits vascular smooth muscle cell activation through Rac1 inactivation. Free Radic Biol Med 2012; 53:109-21.
http://dx.doi.org/10.1016/j.freeradbiomed.2012.03.023
 
50. Aso K, Miyata M, Kubo T, et al. Brachial-ankle pulse wave velocity is useful for evaluation of complications in type 2 diabetic patients. Hypertens Res 2003; 26:807-13.
http://dx.doi.org/10.1291/hypres.26.807
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