Skip to main content
Home
Browse topics
Cardiovascular disorders Chronic kidney disease Diabetes devices & technology GLP-1 receptor agonists Hyperglycemia Hypoglycemia Obesity, diet, & lifestyle interventions SGLT2 inhibitors Type 1 diabetes Type 2 diabetes Browse all topics
EN
EN
In focus
Novel clinical evidence in continuous glucose monitoring Fasting for religion and health in people with diabetes The challenge of type 2 diabetes in children HFpEF & diabetes: Diagnosis and management in the wake of EMPEROR-Preserved Addressing suicide risk in diabetes: Rates and risk factors, HCP fears, and practical advice The SURPASS trials: Summarizing efficacy data on tirzepatide Semaglutide for weight loss: STEP and SELECT trials: Results from the STEP and SELECT trials Why psychosocial care matters DiRECT: Type 2 diabetes remission through weight management
Congress coverage
EASD 58th Annual Meeting 2022 The American Diabetes Association 82nd Scientific Sessions
About us
Medicine Matters Diabetes
EXTENDED SEARCH
Top

03-05-2015 | Diabetic foot | Review | Article

Management of Diabetic Foot Ulcers

Journal: Current Geriatrics Reports

Authors: Rhiannon L. Harries, Keith G. Harding

Publisher: Springer US

Login to get access

Abstract

Diabetes is an increasing urgent global health issue, with an increasing prevalence in those aged 65 or over. Diabetic foot ulcers (DFUs) are a common complication, affecting up to 15 % of those diagnosed with diabetes; they can result in loss of employment, have a significant decrease on quality of life, may lead to limb loss and are costly to healthcare systems. In this paper, we discuss the recent advances in the various management options for diabetic foot ulcers.
Literature
1.•
Bakker K, Apelqvist J, Schaper NC, On behalf of the International Working Group on Diabetic Foot Editorial Board. Practical guidelines on the management and prevention of the diabetic foot 2011. Diabetes Metab Res Rev. 2012;28 Suppl 1:225–31. The basic principles of prevention and treatment of diabetic foot disease described in these guidelines are based on the International Consensus on the Diabetic Foot. PubMedCrossRef
2.
Diabetes UK. The State of the Nation 2014: Diabetes in 2014. London. Diabetes UK, 2014. http://​www.​diabetes.​org.​uk/​Documents/​About%20​Us/​What%20​we%20​say/​State%20​of%20​the%20​nation%20​2014.​pdf Accessed 29.01.15
3.
Centre for Disease Control and Prevention. National diabetes statistics report, 2104. Atlanta. Centre for Disease Control and Prevention, 2014. http://​www.​cdc.​gov/​diabetes/​pubs/​statsreport14/​national-diabetes-report-web.​pdf Accessed 29.01.15
4.
Singh N, Armstrong D, Lipsky B. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293:271–8.CrossRef
5.
Reiber GE. Epidemiology of foot ulcers and amputations in the diabetic foot. In: Bowker JH, Pfeifer MA, editors. The Diabetic Foot. St Louis: Mosby; 2001. p. 13–32.
6.
Kerr M. Foot care for people with diabetes: the economic case for change. NHS Diabetes and Kidney Care, 2012.
7.
Armstrong DG, Lavery LA, et al. Activity patterns of patients with diabetic foot ulcers: patients with active ulcers may not adhere to a standard pressure offloading regimen. Diabetes Care. 2003;26:2595–7.PubMedCrossRef
8.
Mueller MJ, Diamond JE, Sinacore DR, et al. Total contact casting in treatment of diabetic plantar ulcers. Diabetes Care. 1989;12(6):384–8.PubMedCrossRef
9.
Ganguly S, Chakraborty K, Mandal PJ, et al. A comparative study between total contact casting and conventional dressings in the non-surgical management of diabetic plantar foot ulcers. J Indian Med Assoc. 2008;106:237–9.PubMed
10.
Armstrong DG, Nguyen HC, Lavery LA, et al. Off-loading the diabetic foot wound: a randomized clinical trial. Diabetes Care. 2001;24(6):1019–22.PubMedCrossRef
11.
Armstrong DG, Lavery LA, Wu S, Boulton AJM. Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial. Diabetes Care. 2005;28(3):551–4.PubMedCrossRef
12.
Caravaggi C, Sganzaroli A, Fabbi M, et al. Nonwindowed nonremovable fiberglass off-loading cast versus removable pneumatic cast (AircastXP Diabetic Walker) in the treatment of neuropathic noninfected plantar ulcers: a randomized prospective trial. Diabetes Care. 2007;30(10):2577–8.PubMedCrossRef
13.
Piaggesi A, Macchiarini S, Rizzo L, et al. An off-the-shelf instant contact casting device for the management of diabetic foot ulcers: a randomized prospective trial versus traditional fiberglass cast. Diabetes Care. 2007;30(3):586–90.PubMedCrossRef
14.
Faglia E, Caravaggi C, Clerici G, et al. Effectiveness of removable walker cast versus nonremovable fiberglass off-bearing cast in the healing of diabetic plantar foot ulcer: a randomized controlled trial. Diabetes Care. 2010;33(7):1419–23.PubMedCentralPubMedCrossRef
15.
Lewis J, Lipp A. Pressure-relieving interventions for treating diabetic foot ulcers. Cochrane Database Syst Rev 2013, Issue 1. Art. No.: CD002302. doi: 10.​1002/​14651858.​CD002302.​pub2.
16.
Ubbink DT, Westerbos SJ, Nelson EA, Vermeulen H. A systematic review of topical negative pressure therapy for acute and chronic wounds. Br J Surg. 2008;95:685–92.PubMedCrossRef
17.
Blume PA, Walters J, Payne W, et al. Comparison of negative pressure wound therapy using vacuum-assisted closure with advanced moist wound therapy in the treatment of diabetic foot ulcers: a multicenter randomized controlled trial. Diabetes Care. 2008;31(4):631–6.PubMedCrossRef
18.
Novinscak T, Zvorc M, Trojko S, et al. Comparison of cost-benefit of the three methods of diabetic ulcer treatment: dry, moist and negative pressure. Acta Med Croatica. 2010;64 Suppl 1:113–5.
19.
Karatepe O, Eken I, Acet E, et al. Vacuum assisted closure improves the quality of life in patients with diabetic foot. Acta Chir Belg. 2011;111(5):298–302.PubMed
20.
Mody GN, Nirmal IA, Duraisamy S, Perakath B. A blinded, prospective, randomized controlled trial of topical negative pressure wound closure in India. Ostomy Wound Manage. 2008;54(12):36–46.PubMed
21.
Londahl M. Hyperbaric oxygen therapy as adjunctive treatment of diabetic foot ulcers. Med Clin N Am. 2013;97:957–80.PubMedCrossRef
22.
Kranke P, Bennett M, Martyn-St James M, et al. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev. 2012;4:CD004123.PubMed
23.
Ma L, Li P, Shi Z, et al. A prospective, randomized, controlled study of hyperbaric oxygen therapy: effects on healing and oxidative stress of ulcer tissue in patients with a diabetic foot ulcer. Ostomy Wound Manage. 2013;59(3):18–24.PubMed
24.
O’Reilly D, Pasricha A, Campbell K, Burke, et al. Hyperbaric oxygen therapy for diabetic ulcers: systematic review and meta-analysis. Int J Technol Assess Health Care. 2013;29(3):269–81.PubMedCrossRef
25.
Game FL, Hinchliffe RJ, Apelqvist J, et al. A systematic review of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev. 2012;28 Suppl 1:119–41.PubMedCrossRef
26.
Steed DL, Donohoe D, Webster MW, Lindsley L, Diabetic ulcer study group. Effect of extensive debridement and treatment on healing of diabetic foot ulcers. J Am Coll Surg. 1996;183:61–4.PubMed
27.
Edwards J, Stapley S. Debridement of diabetic foot ulcers. Cochrane Database Syst Rev. 2010;1:CD003556. doi:10.​1002/​14651858.PubMed
28.
Gray D, Acton C, Chadwick P, et al. Consensus guidance for the use of debridement techniques in the UK 2011; 7: 77–84.
29.
Ennis WJ, Valdes W, Gainer M, Meneses P. Evaluation of clinical effectiveness of MIST ultrasound for the healing of chronic wounds. Adv Skin Wound Care. 2006;19:437–46.PubMedCrossRef
30.
Wounds UK. Use of the larvae from the Greenbottle fly Wounds UK. Effective debridement in a changing NHS: a UK consensus. London: Wounds UK, 2013. Available from: www.​wounds-uk.​com. Accessed 29.01.15.
31.
Jensen JL, Seeley J, Gillin B. Diabetic foot ulcerations: a controlled, randomized comparison of two moist wound healing protocols: Carrasyn hydrogel wound dressing and wet-to-moist saline gauze. Adv Wound Care. 1998;11(7):1–4.PubMed
32.
D’Hemecourt PA, Smiell JM, Karim MR. Sodium carboxymethyl cellulose aqueous-based gel vs becaplermin gel in patients with nonhealing lower extremity diabetic ulcers. Wounds. 1998;10(3):69–75.
33.
Gregg EW, Sorlie P, Paulose-Ram R, et al. Prevalence of lower-extremity disease in the US adult population >=40 years of age with and without diabetes: 1999–2000 national health and nutrition examination survey. Diabetes Care. 2004;27:1591–7.PubMedCrossRef
34.
Dolan NG, Lui K, Criqui MH, et al. Peripheral arterial disease, diabetes, and reduced lower extremity functioning. Diabetes Care. 2002;25:113–20.PubMedCrossRef
35.
Mayfield JA, Reiber GE, Sanders LJ, et al. Preventative foot care in diabetes. Diabetes Care. 2004;27:S63–4.PubMedCrossRef
36.
Norgen L, Hiatt WR, Dormandy JA, et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg. 2007;45:S5–67.CrossRef
37.
Faglia E, Dalla Paola L, Clerici G, et al. Peripheral angioplasty as the first-choice revascularization procedure in diabetic patients with critical limb ischaemia: prospective study of 993 consecutive patients hospitalized and followed between 1999 and 2003. Eur J Vasc Endovasc Surg. 2005;29:620–7.PubMedCrossRef
38.
Sumpio BE, Forsythe RO, Ziegler KR, et al. Clinical implications of the angiosome model in peripheral arterial disease. J Vasc Surg. 2013;58:814–26.PubMedCrossRef
39.
Vogel TR, Dombrovskiy VY, Haser PB, Graham AM. Evaluating preventable adverse safety events after elective lower extremity procedures. J Vasc Surg. 2011;54:706–13.PubMedCrossRef
40.
Adam DJ, Beard JD, Cleveland T, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomized controlled trial. Lancet. 2005;366:1925–34.PubMedCrossRef
41.
Neville R, Singh N, Jamil T, et al. Revascularization for wound healing: are endovascular techniques as good as open bypass. Presented at the Society for Clinical Vascular Surgery 35th Annual Symposium, Naples, Florida, 2007.
42.
Piaggesi A, Schipani E, Campi F, et al. Conservative surgical approach versus non-surgical management for diabetic neuropathic foot ulcers: a randomised trial. Diabet Med. 1998;15:412–7.PubMedCrossRef
43.
Mueller MJ, Sinacore DR, Hastings MK, et al. Effect of Achilles tendon lengthening on neuropathic plantar ulcers: a randomized clinical trial. J Bone Joint Surg Am. 2003;85-A:1436–45.PubMed
44.
Fleischli JE, Anderson RB, Davis WH. Dorsiflexion metatarsal osteotomy for treatment of recalcitrant diabetic neuropathic ulcers. Foot Ankle Int. 1999;20:80–5.PubMedCrossRef
45.
Clemens MW, Parikh P, Hall MM, et al. External fixators as an adjunct to wound healing. Foot Ankle Clin. 2008;13:145–56.PubMedCrossRef
46.
Armstrong DG, Lavery LA, Vazquez JR, et al. Clinical efficacy of the first metatarsophalangeal joint arthroplasty as a curative procedure for hallux interphalangeal joint wounds in persons with diabetes. Diabetes Care. 2003;26:3284–7.PubMedCrossRef
47.
Foster AVM, Greenhill MT, Edmonds ME. Comparing two dressings in the treatment of diabetic foot ulcers. J Wound Care. 1994;3(5):224–8.
48.
Jeffcoate WJ, Price PE, Phillips CJ, et al. Randomised controlled trial of the use of three dressing preparations in the management of chronic ulceration of the foot in diabetes. Health Technol Assess. 2009;13:1–110.PubMed
49.
Clever HU, Dreyer M. Comparing two wound dressings for the treatment of neuropathic diabetic foot ulcers. Proceedings of the 5th European Conference on Advances in Wound Management; 1995, 21–24 November; Harrogate, UK. Harrogate, UK, 1995: 201–3.
50.
Blackman JD, Senseng D, Quinn L, Mazzone T. Clinical evaluation of a semipermeable polymeric membrane dressing for the treatment of chronic diabetic foot ulcers. Diabetes Care. 1994;17(4):322–5.PubMedCrossRef
51.
Ahroni JH, Boyko EJ, Pecoraro RE. Diabetic foot ulcer healing: extrinsic vs intrinsic factors. Wounds. 1993;5(5):245–55.
52.
Donaghue VM, Chrzan JS, Rosenblum BI, et al. Evaluation of a collagen-alginate wound dressing in the management of diabetic foot ulcers. Adv Wound Care. 1998;11(3):114–9.PubMed
53.
Lalau JD, Bresson R, Charpentier P, et al. Efficacy and tolerance of calcium alginate versus Vaseline gauze dressings in the treatment of diabetic foot lesions. Diabetes Metab. 2002;28(3):223–9.PubMed
54.
Jude EB, Apelqvist J, Spraul M, Martini J. Prospective randomized controlled study of Hydrofiber dressing containing ionic silver or calcium alginate dressings in non- ischaemic diabetic foot ulcers. Diabet Med. 2007;24(3):280–8.PubMedCrossRef
55.
Lawrence JC. The use of iodine as an antiseptic agent. J Wound Care. 1998;7:421–5.PubMed
56.
Michaels JA, Campbell B, King B, et al. Randomised controlled trial and cost-effectiveness analysis of silver-donating antimicrobial dressings for venous leg ulcers (VULCAN trial). Br J Surg. 2009;96:1147–56.PubMedCrossRef
57.
McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action and resistance. Clin Microbiol Rev. 1999;12:147–79.PubMedCentralPubMed
58.
Cutting KF. Honey and contemporary wound care: an overview. Ostomy Wound Manage. 2007;53:49–54.PubMed
59.
Jull AB, Cullum N, Dumville JC, Westby MJ, Deshpande S, Walker N. Honey as a topical treatment for wounds. Cochrane Database Syst Rev. 2015;3:CD005083 [Epub ahead of print].PubMed
60.
Dumville JC, Deshpande S, O’Meara S, Speak K. Hydrocolloid dressings for healing diabetic foot ulcers. Cochrane Database Syst Rev. 2013;8:CD009099. doi:10.​1002/​14651858.​CD009099.​pub3.PubMed
61.
Vermeulen H, Ubbink DT, de Zwart F, et al. Preferences of patients, doctors and nurses regarding wound dressing characteristics: a conjoint analysis. Wound Repair Regen. 2007;15:302–7.PubMedCrossRef
62.
Dumville JC, O’Meara S, Deshpande S, Speak K. Hydrogel dressings for healing diabetic foot ulcers. Cochrane Database Syst Rev. 2013;7:CD009101. doi:10.​1002/​14651858.​CD009101.​pub3.PubMed
63.
Zhong SP, Zhang YZ, Lim CT. Tissue scaffolds for skin wound healing and dermal reconstruction. WIREs Nanomed Nanobiotechnol. 2010;2:510–25.CrossRef
64.
Brigido SA, Boc SF, Lopez RC. Effective management of major lower extremity wounds using an acellular regenerative tissue matrix: a pilot study. Orthopedics. 2004;27 Suppl 1:s145–9.PubMed
65.
Brigido SA. The use of an acellular dermal regenerative tissue matrix in the treatment of lower extremity wounds: a prospective 16-week pilot study. Int Wound J. 2006;3:181–7.PubMedCrossRef
66.
Niezgoda JA, Van Gils CC, Frykberg RG, Hodde JP. Randomised clinical trial comparing OASIS Wound Matrix to Regranex Gel for diabetic ulcers. Adv Skin Wound Care. 2005;18(5):258–66.PubMedCrossRef
67.
Reyzelman A, Crews RT, Moore JC, et al. Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study. Int Wound J. 2009;6:196–208.PubMedCrossRef
68.
Gentzkpw GD, Iwasaki SD, Hershon KS, et al. Use of dermagraft, a cultured human dermis, to treat diabetic foot ulcers. Diabetes Care. 1996;19(4):350–4.CrossRef
69.
Hanft JR, Surprenant MS. Healing of chronic foot ulcers in diabetic patients treated with a human fibroblast-derived dermis. J Foot Ankle Surg. 2002;41(5):291–9.PubMedCrossRef
70.
Marston WA, Hanft J, Norwood P, Pollak R, Dermagraft Diabetic Foot Ulcer Group. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care. 2003;26(6):1701–5.PubMedCrossRef
71.
Veves A, Falanga V, Armstrong DG, Sabolinski ML, Apligraf Diabetic Foot Ulcer Study. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicentre clinical trial. Diabetes Care. 2001;24(2):290–5.PubMedCrossRef
72.
Lev-Tov H, Li CS, Dahle S, Isserof RR. Cellular versus acellular matrix devices in treatment of diabetic foot ulcers: study protocol for a comparative efficacy randomized controlled trial. Trials. 2013;14:8. doi:10.​1186/​1745-6215-14-8.PubMedCentralPubMedCrossRef
73.
Armstrong DG, Jude EB. The role of matrix metalloproteinases in wound healing. J Am Podiatr Med Assoc. 2002;92:12–8.PubMedCrossRef
74.
Gibson D, Cullen B, Legerstee R, Harding KG, Schultz G. MMPs Made Easy. Wounds International 2009; 1(1): http://​www.​woundsinternatio​nal.​com Accessed 04.02.2015
75.
Veves A, Sheehan P, Pham HT. A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers. Arch Surg. 2002;137(7):822.7.PubMedCrossRef
76.
Barrientos S, Stojadinovic O, Golinko MS, et al. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008;16:585–601.PubMedCrossRef
77.
Buchberger B, Follmann M, Freyer D, et al. The importance of growth factors for the treatment of chronic wounds in the case of diabetic foot ulcers. GMS Health Technol Assess 2010; 6: Doc12. doi: 10.​3205/​hta000090.
78.
Fu X, Li X, Cheng B, Chen W, Sheng Z. Engineered growth factors and cutaneous wound healing: success and possible questions in the past 10 years. Wound Repair Regen. 2005;13:122–30.PubMedCrossRef
79.
Mulder G, Tallis AJ, Marshall VT, et al. Treatment of nonhealing diabetic foot ulcers with a platelet-derived growth factor gene-activated matrix (GAM501): results of a phase 1/2 trial. Wound Repair Regen. 2009;17(6):772–9.PubMedCrossRef
80.
Blume P, Driver V, Tallis A, et al. Formulated collagen gel accelerates healing rate immediately after application in patients with diabetic neuropathic foot ulcers. Wound Repair Regen. 2011;19(3):302–8.PubMedCentralPubMedCrossRef
81.
Landsman A, Agnew P, Parish L, et al. Diabetic foot ulcers treated with becaplermin and TheraGauze, a moisture-controlling smart dressing: a randomized, multicenter, prospective analysis. J Am Podiatr Med Assoc. 2010;100(3):155–60.PubMedCrossRef
82.
Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care. 1998;21(5):822–7.PubMedCrossRef
83.
Fernández-Montequín JI, Valenzuela-Silva CM, Díaz OG, Cuban Diabetic Foot Study Group, et al. Intra-lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo-controlled, double-blind study. Int Wound J. 2009;6(6):432–43.PubMedCrossRef
84.
Viswanathan V, Pendsey S, Sekar N, Murthy GSR. A phase III study to evaluate the safety and efficacy of recombinant human epidermal growth factor (REGEN-DTM 150) in healing diabetic foot ulcers. Wounds. 2006;18:186–96.
85.
Tsang MW, Wong WK, Hung CS, et al. Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes Care. 2003;26(6):1856–61.PubMedCrossRef
86.
Uchi H, Igarashi A, Urabe K, et al. Clinical efficacy of basic fibroblast growth factor (bFGF) for diabetic ulcer. Eur J Dermatol. 2009;19(5):461–8.PubMed
87.
Gough A, Clapperton M, Rolando N, et al. Randomised placebo-controlled trial of granulocyte-colony stimulating factor in diabetic foot infection. Lancet. 1997;350(9081):855–9.PubMedCrossRef
88.
Blumberg SN, Berger A, Hwang L, et al. The role of stem cells in the treatment of diabetic foot ulcers. Diabetes Res Clin Pract. 2012;96(1):1–9.PubMedCrossRef
89.
Lu D, Chen B, Liang Z. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract. 2011;92(1):26–36.PubMedCrossRef
90.
Yotsu RR, Hagiwara S, Okochi H, Tamaki T. Case series of patients with chronic foot ulcers treated with autologous platelet-rich plasma. J Dermatol. 2015. doi:10.​1111/​1346-8138.​12777 [Epub ahead of print].PubMed
91.
Prompers L, Schaper N, Apelqvist J, et al. Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study. Diabetologia. 2008;51(5):747–55.PubMedCentralPubMedCrossRef
92.
Lavery LA, Armstrong DA, Wunderlich RP, et al. Risk factors for foot infections in individuals with diabetes. Diabetes Care. 2006;29(6):1288–93.PubMedCrossRef
93.••
Lipsky BA, Berendt AR, Cornia PB. Infectious Disease Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. IDSA guidelines. Clin Infect Dis. 2012;54(12):132–73. This document provides useful guidance on the diagnosis and treatment of diabetic foot infection. CrossRef
94.
Edmonds M, Foster AVM, Vowden P. Wound bed preparation for diabetic foot ulcers. In: EWMA Position Document. Wound bed preparation in practice. London: MEP Ltd, 2004. http://​www.​woundsinternatio​nal.​com accessed 29.01.15
95.
Lipsky BA, Peters EJ, Senneville E, et al. Expert opinion on the management of infections in the diabetic foot. Diabetes Metab Res Rev. 2012;28:163–78.PubMedCrossRef
96.
Nelson EA, O’Meara S, Golder S, et al. Systematic review of antimicrobial treatments for diabetic foot ulcers. Diabet Med. 2006;23:348–59.PubMedCrossRef
97.
Vardakas KZ, Horianopoulou M, Falagas ME. Factors associated with treatment failure in patients with diabetic foot infections: an analysis of data from randomised controlled trials. Diabetes Res Clin Pract. 2008;80:344–51.PubMedCrossRef
98.
Crouzet J, Lavinge JP, Richard JL, et al. Diabetic foot infection : a critical review of recent randomised clinical trials on antibiotic therapy. Int J Infect Dis. 2011;15:e601–10.PubMedCrossRef
99.
Peters EJ, Lipsky BA, Berendt AR, et al. A systematic review of the effectiveness of interventions in the management of the infection in the diabetic foot. Diabetes Metab Res Rev. 2012;28:142–62.PubMedCrossRef
100.
Boykin Jr JV. Wound nitric oxide bioactivity: a promising diagnostic indicator for diabetic foot ulcer management. J Wound Ostomy Continence Nurs. 2010;37(1):25–32.PubMedCrossRef
101.
Mikaili P, Moloudizargari M, Aghajanshakeri S. Treatment with topical nitroglycerine may promote the healing process of diabetic foot ulcers. Med Hypotheses. 2014;83(2):172–4.PubMedCrossRef
102.
Aso Y, Tavama K, Takanashi K, et al. Changes in skin blood flow in type 2 diabetes induced by prostacyclin: association with ankle brachial index and plasma thrombomodulin levels. Metabolism. 2001;50(5):568–72.PubMedCrossRef
103.
Mirenda F, LaSpada M, Baccellieri D, et al. Iloprost infusion in diabetic patients with peripheral arterial occlusive disease and foot ulcers. Chir Ital. 2005;57(6):731–5.PubMed
104.
Young MJ, McCardle JE, Randall LE, Barclay JI. Improved survival of diabetic foot ulcer patients 1995–2008: possible impact of aggressive cardiovascular risk management. Diabetes Care. 2008;31(11):2143–7.PubMedCentralPubMedCrossRef
105.
Gulcan E, Gulcan A, Erbilen E, Toker S. Statins may be useful in diabetic foot ulceration treatment and prevention. Med Hypotheses. 2007;69(6):1313–5.PubMedCrossRef
106.
Johansen OE, Birkeland KI, Jørgensen AP, et al. Diabetic foot ulcer burden may be modified by high-dose atorvastatin: a 6-month randomized controlled pilot trial. J Diabetes. 2009;1(3):182–7.PubMedCrossRef
107.
Toker S, Gulcan E, Cayc MK, et al. Topical atorvastatin in the treatment of diabetic wounds. Am J Med Sci. 2009;338(3):201–4.PubMedCrossRef
108.
Marston WA, Group DDFUS. Risk factors associated with healing chronic diabetic foot ulcers: the importance of hyperglycaemia. Ostomy Wound Manage. 2006;52(3):26–8.PubMed
109.
American Diabetes Association. Consensus development conference on diabetic foot wound care. Diabetes Care. 1999;22:1345–60.
110.
National Institute for Health and Care Excellence. NHS Evidence. Type 2 Diabetes: The management of type 2 diabetes May 2009. http://​www.​evidence.​nhs.​uk Accessed 29.01.15
111.
Sue Kirkman M, Briscoe VJ, Clark N, et al. Consensus Development Conference on Diabetes and older adults. Diabetes in older adults: a consensus report. J Am Geriatr Soc. 2012;60(12):2342–56.PubMedCrossRef