**8. Conclusion and future perspective**

Increased ROS production has been suggested as a common pathway linking diverse patho‐ genic mechanisms of diabetic vascular complications. There are numerous evidences from animal studies on the beneficial effect of antioxidant vitamins supplementation in diabetes mellitus, but results from clinical studies are inconclusive. The antioxidant activity of some anti-diabetic drugs has also been shown to contribute significantly to their therapeutic effect. Biflavonoids as antioxidants are promising and attractive natural substances to enrich the current therapy options against diabetes. The overall positive results from animal studies suggest that the role of antioxidants cannot be underestimated in the quest to find effective therapies for diabetic complications. A multi-therapeutic approach to the treatment of diabetic complications might increase the chance of successful therapeutic intervention. In addition to maintaining glycemic control, blockage of pathways involved in the formation of free radicals with antioxidants is a promising approach to the treatment of hyperglycemia-mediated complications in humans. The bioactivity of flavonoids *in vivo* can be greatly influenced by metabolism and bioavailability and this information is limited in many studies. Limited clinical studies have been carried out to support the beneficial effects of flavonoids in the prevention of diabetic complications. In order to achieve the goal of using flavonoids in the management of diabetes mellitus, further investigation on the long and short-term effect of the ingestion of flavonoids in humans is warranted.

[3] Ruhe, R.C. & McDonald, R.B. 2001. Use of antioxidant nutrients in the prevention

Oxidative Stress and Diabetic Complications: The Role of Antioxidant Vitamins and Flavonoids

http://dx.doi.org/10.5772/57282

41

[4] Resnick, H.E. & Howard, B.V. 2002. Diabetes and cardiovascular disease. *Annu Rev*

[5] Fowler, M.J. 2008. Microvascular and macrovascular complications of diabetes. *Clin*

[6] Cook, M.N., Girman, C.J., Stein, P.P., Alexander, C.M. & Holman, R.R. 2005. Glyce‐ mic control continues to deteriorate after sulfonylureas are added to metformin

[7] Kowluru, R.A., Abbas, S.N. & Odenbach, S. 2004. Reversal of hyperglycemia and dia‐ betic nephropathy: effect of reinstitution of good metabolic control on oxidative

[8] Mayor, S. 2008. Intensive glucose lowering arm of diabetes trial is stopped after ex‐

[9] Ismail-Beigi, F., Craven, T., Banerji, M.A., Basile, J., Calles, J., Cohen, R.M., Cuddihy, R., Cushman, W.C., Genuth, S. & Grimm Jr, R.H. 2010. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the

[10] Kawahito, S., Kitahata, H. & Oshita, S. 2009. Problems associated with glucose toxici‐ ty: Role of hyperglycemia-induced oxidative stress. *World J Gastroenterol:* 15(33): 4137.

[11] Ceriello, A. 2003. New insights on oxidative stress and diabetic complications may

[12] Giacco, F. & Brownlee, M. 2010. Oxidative stress and diabetic complications. *Circ Res,*

[13] Zhang, C., Liu, J., Pan, H., Yang, X. & Bian, K. 2011. Mitochondrial dysfunction in‐ duced by excessive ROS/RNS-metabolic cardiovascular disease and traditional Chi‐

[14] Jain, M. 2012. Histopathological changes in diabetic kidney disease. *Clin Queries:*

[15] Lewis, E.J. & Xu, X. 2008. Abnormal Glomerular Permeability Characteristics in Dia‐ betic Nephropathy Implications for the therapeutic use of low–molecular weight

[16] O'Connor, A.S. & Schelling, J.R. 2005. Diabetes and the kidney. *Am J Kidney Dis,*

[17] Marshall, S.M.m& Flyvbjerg, A. 2006. Prevention and early detection of vascular

lead to a "causal" antioxidant therapy. *Diabetes Care,* 26(5): 1589-1596.

nese medicines intervention. *China J Chinese Mat med,* 36(17): 2423.

heparin. *Diabetes Care,* 31(Supplement 2): S202-S207.

complications of diabetes. *Br Med J,* 333(7566): 475.

stress in the kidney of diabetic rats. *J Diabetes Complication,* 18(5): 282-288.

and treatment of type 2 diabetes. *J Am Coll Nutr, 20* (sup5): 363S-369S.

among patients with type 2 diabetes. *Diabetes Care,* 28(5): 995-1000.

ACCORD randomised trial. *The Lancet,* 376(9739): 419-430.

*Med,* 53(1): 245-267.

*Diabetes,* 26(2): 77-82.

107(9): 1058-1070.

*Nephrol,* 1(2): 127-133.

46(4): 766-773.

cess deaths. *Br Med J,* 336(7641): 407.
