HbA1c is a risk factor for cardiovascular disease in association with oxidative stress in patients with type 2 diabetes mellitus

Siva Prasad Palem


Background: Cardiovascular disease (CVD) is a major cause of death in diabetic subjects. Glycaemic status is one of the vital factor involved in vascular complications. It was clear the effect of glycaemia on microvascular complications, but uncertain on macrovascular complications. As we know oxidative stress plays a major role in the development of atherosclerosis and cardiovascular disease. Since oxidative stress is a risk factor for cardiovascular disease, the study has designed to perceive an association between HbA1c and oxidative stress in patients with type 2 diabetes mellitus for early prediction of cardiovascular events.

Methods: 120 subjects were taken into the study, among these 60 type 2 diabetic subjects and remaining 60 subjects were healthy controls. The parameters like HbA1c, MDA and FRAP were estimated by established methods. ‘Kruskal Wallis’ test was used for variables in the parameters and Pearson correlation test was used to perform correlation between HbA1c and oxidative stress.

Results: High level of HbA1c and MDA, low level of FRAP were found in patients with type 2 diabetes than healthy controls. The study was also found HbA1c have positive association with malondialdehyde (MDA) and negative association with FRAP.

Conclusions: HbA1c was positively associated with oxidative stress in patients with type 2 diabetes mellitus. In this scenario, type 2 diabetic patients with high level of HbA1c might have risk of cardiovascular events.


CVD, Ferric reducing ability of plasma, Glycosylated hemoglobin, MDA, Type 2 diabetes mellitus

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Kilpatrick ES, Rigby AS, Atkin SL. Mean blood glucose compared with HbA1c in the prediction of cardiovascular disease in patients with type 1 diabetes. Diabetologia. 2008;51:365-71.

Muntner P, Wildman RP, Reynolds K, Desalvo KB, Chen J, Fonseca V. Relationship between HbA1c level and peripheral arterial disease. Diabetes care. 2005;28(8):1981-7.

Zoungas S, Chalmers J, Ninomiya T, Li Q, Cooper ME, Colagiuri S, et al. Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds. Diabetologia. 2012;55:636-43.

Lakshmi SVV, Padmaja G, Kuppusamy P, Kutala VK. Oxidative stress in cardiovascular disease. Indian J Biochem Biophy. 2009;46:421-40.

Dominiczaks AF. Oxidative stress and cardiovascular disease. Endocrine Abstracts. 2005;9:S23.

Higashi Y, Noma K, Yoshizumi M, Kihara Y. Review Endothelial function and oxidative stress in cardiovascular disease. Circulation J. 2009;73:411-8.

Lipska KJ, Warton EM, Huang ES, Moffet HH, Inzucchi SE, Krumholz HM, et al. HbA1c and risk of severe hypoglycemia in type 2 diabetes. Diabetes Care. 2013;36(11):3535-42.

Ganz ML, Wintfeld N, Li Q, Alas V, Langer J, Hammer M. The association of body mass index with the risk of type 2 diabetes: a case-control study nested in an electronic health record system in the United States. Diabetol Metabol Syndrome 2014;6:50.

Hollander P. Anti-diabetes and anti-obesity medication: Effects on weight in people with diabetes. Diabetes Spectrum 2007;20(3):159-65.

Khan R. Weight gain and Insulin therapy. Br J Diabetes Vascular Disease. 2004;4:264-7.

Dokken BB, Tsao TS. The physiology of body weight regulation:Are we too efficient for our own good? Diabetes Spectrum. 2007;20(3):166-70.

Day C, Bailey CJ. Obesity in the pathogenesis of type 2 diabetes. Br J Diabetes Vascular Disease. 2011;11:55-61.

Jee SH, Sull JW, Park J, Lee SY, Ohrr H, Guallar E, et al. Body mass index and mortality in Korean men and women. N Engl J Med. 2006;355:779-87.

Chen Z, Yang G, Offer A, Zhou M, Smith M, Peto R, et al. Body mass index and mortality in China:a 15-year prospective study of 220000 men. Int J Epidemiol. 2012;41:472-81.

Ni Mhurchu C, Rodgers A, Pan WH, Gu DF, Woodward M; Asia Pacific Cohort Studies Collaboration. Body mass index and cardiovascular disease in the Asia-Pacific Region:an overview of cohorts involving 310000 participants. Int J Epidemiol. 2004;33:751-8.

Song SH, Hardisty CA. Type 2 Diabetes mellitus:a high risk condition for cardiovascular disease irrespective of the different degrees of obesity. Q J Med. 2008;101:875-9.

Klein R, Klein BEK, Moss SE. Is obesity related to microvascular and macrovascular complications in diabetes? The Wisconsin epidemiological study of diabetic retinopathy. Arch Intern Med. 1997;157:650-6.

Ong CR, Molyneaux LM, Constantino MI, Twigg SM, Yue DK. Long term efficacy of metformin therapy in nonobese individuals with type 2 diabetes. Diabetes care. 2006;29:2361-4.

Turner RC, Millns H, Holman RR. Coronary heart disease and risk factors in NIDDM – experience from the United Kingdom Prospective Diabetes Study. Diabetol. 1997;40:121-2.

Nathan DM, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia. 2007;50:2239-44.

Little RR, Roberts WL. A Review of variant hemoglobins interfering with hemoglobin A1c measurement. J Diabetes Sci Tech. 2009;3.3:446-51.

Pasupathi P, Manivannan P, Uma M, Deepa M. Glycated haemoglobin (HbA1c) as a stable indicator of type 2 diabetes. Int J Pharm Biomed Res. 2010;1.2:53-6.

Miller ME, Bonds DE, Gerstein HC, Seaquist ER, Bergenstal RM, Calles-Escandon J, et al. The effect of baseline characteristics, glycaemia treatment approach and glycated haemoglobin concentration on the risk of severe hypoglycaemia:post hoc epidemiological analysis of the ACCORD study. BMJ. 2010;340:b5444.

Hong LF, Li XL, Guo YL, Luo SH, Zhu CG, Qing P, et al. Glycosylated hemoglobin A1c as a marker predicting the severity of coronary artery disease and early outcome in patients with stable angina. Lipids Health Disease. 2014;13:89.

Ravipati G, Aronow WS, Ahn C, Kumbar S, Saulle LN, et al. Association of hemoglobin A(1c) level with the severity of coronary artery disease in patients with diabetes mellitus. Am J Cardiol. 2006;97:968-9.

Saleem T, Mohammad KH, Abdel-Fattah MM, Abbasi AH. Association of glycosylated hemoglobin level and diabetes mellitus duration with the severity of coronary artery disease. Diab Vasc Dis Res. 2008;5:184-9.

Ikeda F, Doi Y, Ninomiya T, Hirakawa Y, Mukai N, Hata J, et al. Haemoglobin A1c even within non-diabetic level is a predictor of cardiovascular disease in general Japanese population: The Hisayama Study. Cardiovascular Diabetol. 2013;12:164.

Reaven PD, Moritz TE, Schwenke DC, Anderson RJ, Criqui M, Detrano R, et al. Intensive glucose lowering therapy reduces cardiovascular disease events in veterans affairs diabetes trial participants with lower calcified coronary atherosclerosis. Diabetes. 2009;58(11):2642-8.

Bots SH, Graaf YV, Nathoe HMW, Borst GJ, Kappelle JL, Visseren FLJ, et al. The influence of baseline risk on the relation between HbA1c and risk for new cardiovascular events and mortality in patients with type 2 diabetes and symptomatic cardiovascular disease. Cardiovascular Diabetol. 2016;15:101.

Selvin E, Coresh J, Golden SH, Boland LL, Brancati FL, Steffes MW, et al. Glycemic control, atherosclerosis and risk factors for cardiovascular disease in individuals with diabetes. Diabetes Care. 2005;28:1965-73.

Sasso FC, Carbonara O, Nasti R, Campana B, Marfella R, Torella M, et al. Glucose metabolism and coronary heart disease in patients with normal glucose tolerance. JAMA. 2004;291:1857-63.

Adams RJ, Appleton SL, Hill CL, Wilson DH, Taylor AW, Chittleborough CR, et al. Independent association of HbA1c and incident cardiovascular disease in people without diabetes. Obesity 2009;17:559-63.

Pasaoglu H, Sancak B, Bukan N. Lipid peroxidation and resistance to oxidation in patients with type 2 diabetes mellitus. Tohoku J Exp Med. 2004;203:211-8.

Kolhe SM, Khanwelkar CC. Oxidative stress, antioxidants and metformin in type 2 diabetes mellitus. J Med Educ Res. 2013;3(2):25-32.

Alam R, Khan S, Salman KA. MDA and antioxidant status in type 2 diabetes mellitus. NJIRM. 2013;4.6:75-8.

Wolff SP, Dean RT. Glucose auto-oxidation and protein modification. The potential role of ‘auto-oxidative glycosylation’ in diabetes. Biochem J. 1987;245:243-50.

Jain SK, Lim G. Pyridoxine and pyridoxamine inhibits superoxide radicals and prevents lipid peroxidation, protein, glycosylation and Na+P ATPase activity reduction in high glucose treated human erythrocytes. Free Radic Bio Med. 2001;30:232-7.

Noberasco G, Odetti P, Boeri D, Maiello M, Adezati L. Malondialdehyde (MDA) level in diabetic subjects. Relationship with blood glucose and glycosylated hemoglobin. Biomed Pharmacother. 1991;45(1-5):193-6.

Marchi ED, Baldassari F, Bononi A, Wieckowski MR, Pinton P. Review Oxidative stress in cardiovascular disease and Obesity:Role of p66Shc and protein kinase C. Oxid Med Cell Longev. 2013;2013:564961.