Objective. The effect of a proprietary formulation of trans-resveratrol (t-RSV) on manifestations of diabetic foot syndrome (DFS) was studied in type 2 diabetic patients with newly diagnosed diabetic foot ulcers. Method. Placebo-controlled, examiner-blinded, parallel-group randomized controlled pilot clinical trial (ACTRN Clinical Trial Registry number 12610000629033) involving 24 patients with DFS (15 males and 9 females, average age of years) divided into the placebo and RSV-treatment groups was performed. 50？mg of t-RSV or placebo capsules was given to each patient twice a day over a 60-day time period. Results. Reduction in the parameters reflecting diabetic ulcer size was more profound in the RSV group as compared to placebo. RSV-treated patients also had a marginally improved performance in the foot pressure test. A statistically significant decline in the plasma fibrinogen level, but not CRP, was also found in the RSV-treated patients. Some improvement in the plasma lipid profile and fasting glucose levels were not related to RSV-treatment, since they have been seen on both the RSV and placebo groups, revealing the effectiveness of medical supervision and education in the newly diagnosed patients with DFS. Conclusion. t-RSV supplementation promotes reduction of the foot ulcer size and reduces plasma fibrinogen level in type 2 diabetic patients. 1. Introduction The International Diabetes Federation estimates that there are currently 285 million diabetic patients worldwide. This represents a twofold increase in the number of individuals affected by diabetes since 2000 [1]. A further increase in the number of diabetic patients of ~7 million per year is projected for the near future. Up to 25% of diabetics are likely to develop diabetic foot syndrome at some time during the course of their disease [2, 3]. In general terms, diabetic ulcers represent the most severe and persistent cause of chronic ulceration in the human body. Poorly managed diabetic foot syndrome eventually leads to lower limb amputation [4]. Overall life expectancy of patients with diabetic foot syndrome, even in industrialized countries, is reduced by at least 10 years [5]. Five-year mortality rates in newly diagnosed patients might reach 55% and rise to 74% after lower limb amputation [6, 7]. These remarkable values exceed known mortality rates for breast, colon, and prostate cancers [8]. There are significant deficiencies in the understanding of the pathophysiological mechanisms behind diabetic ulceration. It is generally believed that neuropathy, peripheral arterial disease, and
References
[1]
“Type 2 diabetes—time to change our approach (editorial),” The Lancet, vol. 375, no. 9733, 2193 pages, 2010.
[2]
A. J. Boulton, L. Vileikyte, G. Ragnarson-Tennvall, and J. Apelqvist, “The global burden of diabetic foot disease,” The Lancet, vol. 366, no. 9498, pp. 1719–1724, 2005.
[3]
N. Singh, D. G. Armstrong, and B. A. Lipsky, “Preventing foot ulcers in patients with diabetes,” Journal of the American Medical Association, vol. 293, no. 2, pp. 217–228, 2005.
[4]
K. Bakker, Z. G. Abbas, and S. Pendsey, “Step by step, improving diabetic foot care in the developing world,” Practical Diabetes International, vol. 23, no. 8, pp. 365–369, 2006.
[5]
J. van Baal, R. Hubbard, F. Game, and W. Jeffcoate, “Mortality associated with acute charcot foot and neuropathic foot ulceration,” Diabetes Care, vol. 33, no. 5, pp. 1086–1089, 2010.
[6]
P. K. Moulik, R. Mtonga, and G. V. Gill, “Amputation and mortality in new-onset diabetic foot ulcers stratified by etiology,” Diabetes Care, vol. 26, no. 2, pp. 491–494, 2003.
[7]
E. Faglia, F. Favales, and A. Morabito, “New ulceration, new major amputation, and survival rates in diabetic subjects hospitalized for foot ulceration from 1990 to 1993: a 6.5-year follow-up,” Diabetes Care, vol. 24, no. 1, pp. 78–83, 2001.
[8]
J. M. Robbins, G. Strauss, D. Aron, J. Long, J. Kuba, and Y. Kaplan, “Mortality rates and diabetic foot ulcers: is it time to communicate mortality risk to patients with diabetic foot ulceration?” Journal of the American Podiatric Medical Association, vol. 98, no. 6, pp. 489–493, 2008.
[9]
D. Malgrange, “Physiopathology of the diabetic foot,” Revue de Medecine Interne, vol. 29, supplement 2, pp. S231–S237, 2008.
[10]
R. Blakytny and E. B. Jude, “Altered molecular mechanisms of diabetic foot ulcers,” International Journal of Lower Extremity Wounds, vol. 8, no. 2, pp. 95–104, 2009.
[11]
C. Weigelt, B. Rose, U. Poschen et al., “Immune mediators in patients with acute diabetic foot syndrome,” Diabetes Care, vol. 32, no. 8, pp. 1491–1496, 2009.
[12]
L. Dalla Paola and E. Faglia, “Treatment of diabetic foot ulcer: an overview strategies for clinical approach,” Current Diabetes Reviews, vol. 2, no. 4, pp. 431–447, 2006.
[13]
A. O'Loughlin, C. McIntosh, S. F. Dinneen, and T. O'Brien, “Review paper: basic concepts to novel therapies: a review of the diabetic foot,” International Journal of Lower Extremity Wounds, vol. 9, no. 2, pp. 90–102, 2010.
[14]
W. A. Marston, “Dermagraft, a bioengineered human dermal equivalent for the treatment of chronic nonhealing diabetic foot ulcer,” Expert Review of Medical Devices, vol. 1, no. 1, pp. 21–31, 2004.
[15]
I. M. Petyaev, “Carotenoid particles and uses thereof,” August 2012, WO 2012/104576. International application number PCT/GD2012/00075.
[16]
Y. K. Bashmakov, S. Assaad-Khalil, and I. M. Petyaev, “Resveratrol may be beneficial in treatment of diabetic foot syndrome,” Medical Hypotheses, vol. 77, no. 3, pp. 364–367, 2011.
[17]
N. C. Schaper, J. Apelqvist, and K. Bakker, “The international consensus and practical guidelines on the management and prevention of the diabetic foot,” Current Diabetes Reports, vol. 3, no. 6, pp. 475–479, 2003.
[18]
J. W. Brodsky, “Staging and classification of foot lesions in diabetic patients,” in Levin and O’Neals; the Diabetic Foot, pp. 273–275, Mosby, St. Louis, Mo, USA, 6th edition, 2001.
[19]
A. Bryant, K. Singer, and P. Tinley, “Comparison of the reliability of plantar pressure measurements using the two-step and midgait methods of data collection,” Foot and Ankle International, vol. 20, no. 10, pp. 646–650, 1999.
[20]
M. Van Der Leeden, J. H. M. Dekker, P. C. Siemonsma, S. S. Lek-Westerhof, and M. P. M. Steultjens, “Reproducibility of plantar pressure measurements in patients with chronic arthritis: a comparison of one-step, two-step, and three-step protocols and an estimate of the number of measurements required,” Foot and Ankle International, vol. 25, no. 10, pp. 739–744, 2004.
[21]
G. V. Zammit, H. B. Menz, and S. E. Munteanu, “Reliability of the TekScan MatScan system for the measurement of plantar forces and pressures during barefoot level walking in healthy adults,” Journal of Foot and Ankle Research, vol. 3, no. 1, article 11, 2010.
[22]
J. K. Bhatt, S. Thomas, and M. J. Nanjan, “Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus,” Nutrition Research, vol. 32, no. 7, pp. 537–541, 2012.
[23]
J. Tomé-Carneiro, M. Gonzálvez, M. Larrosa et al., “One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease,” American Journal of Cardiology, vol. 110, no. 3, pp. 356–363, 2012.
[24]
B. Agarwal, M. J. Campen, M. M. Channell et al., “Resveratrol for primary prevention of atherosclerosis: clinical trial evidence for improved gene expression in vascular endothelium,” International Journal of Cardiology, vol. 166, no. 1, pp. 246–248, 2013.
[25]
M. M. Poulsen, P. F. Vestergaard, B. F. Clasen et al., “High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin Sensitivity, and body composition,” Diabetes, vol. 62, no. 4, pp. 1186–1195, 2013.
