UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Management of diabetic foot ulcers

Authors
David G Armstrong, DPM, MD, PhD
Richard J de Asla, MD
David K McCulloch, MD
Section Editors
John F Eidt, MD
Joseph L Mills, Sr, MD
David M Nathan, MD
Deputy Editor
Kathryn A Collins, MD, PhD, FACS

INTRODUCTION

The lifetime risk of a foot ulcer in patients with diabetes (type 1 or 2) may be as high as 25 percent [1-3]. Diabetic foot ulcers are a major cause of morbidity and mortality, accounting for approximately two-thirds of all nontraumatic amputations performed in the United States [4,5]. Infected or ischemic diabetic foot ulcers account for approximately 25 percent of all hospital stays for patients with diabetes [6]. These observations illustrate the importance of prompt and appropriate treatment of foot ulcers in patients with diabetes.

The management of diabetic foot ulcers, including local wound care, use of mechanical offloading, treatment of infection, and indications for revascularization are reviewed here. The evaluation of the diabetic foot and specific management of the threatened limb are reviewed separately. (See "Evaluation of the diabetic foot" and "Treatment of chronic lower extremity critical limb ischemia".)

ETIOLOGY

Risk factors that can lead to foot wounds in patients with diabetes include loss of protective sensation due to neuropathy, prior ulcers or amputations, foot deformity leading to excess pressure, external trauma, infection, and the effects of chronic ischemia, typically due to peripheral artery disease [1]. Patients with diabetes also have an increased risk for nonhealing related to mechanical and cytogenic factors, as well as a high prevalence of peripheral artery disease. (See "Evaluation of the diabetic foot", section on 'Risk factors' and "Wound healing and risk factors for non-healing", section on 'Risk factors for non-healing'.)

ULCER CLASSIFICATION

The first step in managing diabetic foot ulcers is classifying the ulcer. Classification is based upon clinical evaluation of the extent of the ulcer and assessment of the vascular status of the foot, which help determine the nature and intensity of treatment. (See "Clinical assessment of wounds" and "Evaluation of the diabetic foot", section on 'Wound evaluation' and "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities".)

University of Texas system — An earlier and commonly used classification system was originally proposed by Wagner [7]. This classification was based upon clinical evaluation (depth of ulcer and presence of necrosis) alone and did not account for variability in the vascular status of the foot. An update to the Wagner system was introduced at the University of Texas (UT), San Antonio in the United States [8]. While similar to Wagner in its first three categories, this later system eliminated grades 4 and 5 and added stages A-D for each of the grades [9]. The UT system was the first diabetic foot ulcer classification to be validated [10].

                              

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Thu Aug 11 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Boulton AJ, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care 2008; 31:1679.
  2. National Diabetes Data Group. Diabetes in America, 2nd Edition, National Institutes of Health, Washington, D.C p.409.
  3. American Diabetes Association. Clinical Practice Recommendations: foot care in patients with diabetes mellitus. Diabetes Care 1996; 19:S23.
  4. Ramsey SD, Newton K, Blough D, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care 1999; 22:382.
  5. 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.
  6. American Diabetes Association: Statistics about diabetes: diabetes from the national diabetes statistics report, 2014 (released 06/10/14). http://www.diabetes.org/diabetes-basics/statistics/ (Accessed on September 02, 2015).
  7. Wagner FW Jr. The dysvascular foot: a system for diagnosis and treatment. Foot Ankle 1981; 2:64.
  8. Lavery LA, Armstrong DG, Harkless LB. Classification of diabetic foot wounds. J Foot Ankle Surg 1996; 35:528.
  9. Oyibo SO, Jude EB, Tarawneh I, et al. A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems. Diabetes Care 2001; 24:84.
  10. Armstrong DG, Lavery LA, Harkless LB. Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation. Diabetes Care 1998; 21:855.
  11. Zhan LX, Branco BC, Armstrong DG, Mills JL Sr. The Society for Vascular Surgery lower extremity threatened limb classification system based on Wound, Ischemia, and foot Infection (WIfI) correlates with risk of major amputation and time to wound healing. J Vasc Surg 2015; 61:939.
  12. Armstrong DG, Mills JL. Juggling risk to reduce amputations: The three-ring circus of infection, ischemia and tissue loss-dominant conditions, Wound Medicine 2013; 1:13. http://www.sciencedirect.com/science/article/pii/S2213909513000037.
  13. Mills JL Sr, Conte MS, Armstrong DG, et al. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg 2014; 59:220.
  14. Schaper NC. Diabetic foot ulcer classification system for research purposes: a progress report on criteria for including patients in research studies. Diabetes Metab Res Rev 2004; 20 Suppl 1:S90.
  15. Kaufman J, Breeding L, Rosenberg N. Anatomic location of acute diabetic foot infection. Its influence on the outcome of treatment. Am Surg 1987; 53:109.
  16. Jones EW, Peacock I, McLain S, et al. A clinico-pathological study of diabetic foot ulcers. Diabet Med 1987; 4:475.
  17. Shea JD. Pressure sores: classification and management. Clin Orthop Relat Res 1975; :89.
  18. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012; 54:e132.
  19. Hingorani A, LaMuraglia GM, Henke P, et al. The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. J Vasc Surg 2016; 63:3S.
  20. Khanolkar MP, Bain SC, Stephens JW. The diabetic foot. QJM 2008; 101:685.
  21. Brodsky JW. The diabetic foot. In: Surgery and Ankle, 8th ed, Coughlin MJ, Mann RA, Saltzman CL. (Eds), Mosby, Philadelphia 2007. p.1281.
  22. Fernando ME, Seneviratne RM, Tan YM, et al. Intensive versus conventional glycaemic control for treating diabetic foot ulcers. Cochrane Database Syst Rev 2016; :CD010764.
  23. Armstrong DG, Hanft JR, Driver VR, et al. Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial. Diabet Med 2014; 31:1069.
  24. Fox JD, Baquerizo-Nole KL, Macquhae F, et al. Statins may be associated with six-week diabetic foot ulcer healing. Wound Repair Regen 2016; 24:454.
  25. Isaac AL, Armstrong DG. Negative pressure wound therapy and other new therapies for diabetic foot ulceration: the current state of play. Med Clin North Am 2013; 97:899.
  26. Sheehan P, Jones P, Giurini JM, et al. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Plast Reconstr Surg 2006; 117:239S.
  27. Wrobel JS, Charns MP, Diehr P, et al. The relationship between provider coordination and diabetes-related foot outcomes. Diabetes Care 2003; 26:3042.
  28. Miller JD, Salloum M, Button A, et al. How can I maintain my patient with diabetes and history of foot ulcer in remission? Int J Low Extrem Wounds 2014; 13:371.
  29. Armstrong DG, Mills JL. Toward a change in syntax in diabetic foot care: prevention equals remission. J Am Podiatr Med Assoc 2013; 103:161.
  30. 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; 51:747.
  31. Lebrun E, Tomic-Canic M, Kirsner RS. The role of surgical debridement in healing of diabetic foot ulcers. Wound Repair Regen 2010; 18:433.
  32. Karavan M, Olerud J, Bouldin E, et al. Evidence-based chronic ulcer care and lower limb outcomes among Pacific Northwest veterans. Wound Repair Regen 2015; 23:745.
  33. Steed DL, Donohoe D, Webster MW, Lindsley L. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic Ulcer Study Group. J Am Coll Surg 1996; 183:61.
  34. Frykberg RG, Zgonis T, Armstrong DG, et al. Diabetic foot disorders. A clinical practice guideline (2006 revision). J Foot Ankle Surg 2006; 45:S1.
  35. Dumville JC, O'Meara S, Deshpande S, Speak K. Hydrogel dressings for healing diabetic foot ulcers. Cochrane Database Syst Rev 2013; :CD009101.
  36. Opletalová K, Blaizot X, Mourgeon B, et al. Maggot therapy for wound debridement: a randomized multicenter trial. Arch Dermatol 2012; 148:432.
  37. Armstrong DG, Salas P, Short B, et al. Maggot therapy in "lower-extremity hospice" wound care: fewer amputations and more antibiotic-free days. J Am Podiatr Med Assoc 2005; 95:254.
  38. Wu L, Norman G, Dumville JC, et al. Dressings for treating foot ulcers in people with diabetes: an overview of systematic reviews. Cochrane Database Syst Rev 2015; :CD010471.
  39. Bergin SM, Wraight P. Silver based wound dressings and topical agents for treating diabetic foot ulcers. Cochrane Database Syst Rev 2006; :CD005082.
  40. 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; 17:322.
  41. Marston WA, Hanft J, Norwood P, et al. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care 2003; 26:1701.
  42. Margolis DJ, Kantor J, Santanna J, et al. Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes Care 2001; 24:483.
  43. 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.
  44. 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; 111:298.
  45. 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; 54:36.
  46. Dumville JC, Hinchliffe RJ, Cullum N, et al. Negative pressure wound therapy for treating foot wounds in people with diabetes mellitus. Cochrane Database Syst Rev 2013; :CD010318.
  47. Armstrong DG, Lavery LA, Diabetic Foot Study Consortium. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet 2005; 366:1704.
  48. 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; 31:631.
  49. McCallon SK, Knight CA, Valiulus JP, et al. Vacuum-assisted closure versus saline-moistened gauze in the healing of postoperative diabetic foot wounds. Ostomy Wound Manage 2000; 46:28.
  50. Eginton MT, Brown KR, Seabrook GR, et al. A prospective randomized evaluation of negative-pressure wound dressings for diabetic foot wounds. Ann Vasc Surg 2003; 17:645.
  51. Ford CN, Reinhard ER, Yeh D, et al. Interim analysis of a prospective, randomized trial of vacuum-assisted closure versus the healthpoint system in the management of pressure ulcers. Ann Plast Surg 2002; 49:55.
  52. Etoz A, Ozgenel Y, Ozcan M. The use of negative pressure wound therapy on diabetic foot ulcers. Wounds 2004; 16:264.
  53. Philbeck TE, Schroeder WJ, Whittington KT. Vacuum-assisted closure therapy for diabetic foot ulcers: clinical and cost analysis. Home Health Consultant 2001; 8:1.
  54. Armstrong DG, Lavery LA, Abu-Rumman P, et al. Outcomes of subatmospheric pressure dressing therapy on wounds of the diabetic foot. Ostomy Wound Manage 2002; 48:64.
  55. Andros G, Armstrong DG, Attinger CE, et al. Consensus statement on negative pressure wound therapy (V.A.C. Therapy) for the management of diabetic foot wounds. Ostomy Wound Manage 2006; Suppl:1.
  56. Veves A, Falanga V, Armstrong DG, et al. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care 2001; 24:290.
  57. Naughton G, Mansbridge J, Gentzkow G. A metabolically active human dermal replacement for the treatment of diabetic foot ulcers. Artif Organs 1997; 21:1203.
  58. Gentzkow GD, Iwasaki SD, Hershon KS, et al. Use of dermagraft, a cultured human dermis, to treat diabetic foot ulcers. Diabetes Care 1996; 19:350.
  59. Caravaggi C, De Giglio R, Pritelli C, et al. HYAFF 11-based autologous dermal and epidermal grafts in the treatment of noninfected diabetic plantar and dorsal foot ulcers: a prospective, multicenter, controlled, randomized clinical trial. Diabetes Care 2003; 26:2853.
  60. Hanft JR, Surprenant MS. Healing of chronic foot ulcers in diabetic patients treated with a human fibroblast-derived dermis. J Foot Ankle Surg 2002; 41:291.
  61. Puttirutvong P. Meshed skin graft versus split thickness skin graft in diabetic ulcer coverage. J Med Assoc Thai 2004; 87:66.
  62. Rose JF, Giovinco N, Mills JL, et al. Split-thickness skin grafting the high-risk diabetic foot. J Vasc Surg 2014; 59:1657.
  63. Edmonds M, Bates M, Doxford M, et al. New treatments in ulcer healing and wound infection. Diabetes Metab Res Rev 2000; 16 Suppl 1:S51.
  64. Barber C, Watt A, Pham C, et al. Influence of bioengineered skin substitutes on diabetic foot ulcer and venous leg ulcer outcomes. J Wound Care 2008; 17:517.
  65. Kirsner RS, Warriner R, Michela M, et al. Advanced biological therapies for diabetic foot ulcers. Arch Dermatol 2010; 146:857.
  66. Blozik E, Scherer M. Skin replacement therapies for diabetic foot ulcers: systematic review and meta-analysis. Diabetes Care 2008; 31:693.
  67. Martí-Carvajal AJ, Gluud C, Nicola S, et al. Growth factors for treating diabetic foot ulcers. Cochrane Database Syst Rev 2015; :CD008548.
  68. 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; 21:822.
  69. http://www.regranex.com/ (Accessed on October 07, 2010).
  70. http://www.drugs.com/pro/regranex.html (Accessed on February 10, 2016).
  71. Kranke P, Bennett M, Roeckl-Wiedmann I, Debus S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev 2004; :CD004123.
  72. Stoekenbroek RM, Santema TB, Legemate DA, et al. Hyperbaric oxygen for the treatment of diabetic foot ulcers: a systematic review. Eur J Vasc Endovasc Surg 2014; 47:647.
  73. Goldman RJ. Hyperbaric oxygen therapy for wound healing and limb salvage: a systematic review. PM R 2009; 1:471.
  74. Roeckl-Wiedmann I, Bennett M, Kranke P. Systematic review of hyperbaric oxygen in the management of chronic wounds. Br J Surg 2005; 92:24.
  75. Wang C, Schwaitzberg S, Berliner E, et al. Hyperbaric oxygen for treating wounds: a systematic review of the literature. Arch Surg 2003; 138:272.
  76. Liu R, Li L, Yang M, et al. Systematic review of the effectiveness of hyperbaric oxygenation therapy in the management of chronic diabetic foot ulcers. Mayo Clin Proc 2013; 88:166.
  77. Margolis DJ, Gupta J, Hoffstad O, et al. Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: a cohort study. Diabetes Care 2013; 36:1961.
  78. Fedorko L, Bowen JM, Jones W, et al. Hyperbaric Oxygen Therapy Does Not Reduce Indications for Amputation in Patients With Diabetes With Nonhealing Ulcers of the Lower Limb: A Prospective, Double-Blind, Randomized Controlled Clinical Trial. Diabetes Care 2016; 39:392.
  79. Faglia E, Favales F, Aldeghi A, et al. Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. Diabetes Care 1996; 19:1338.
  80. Duzgun AP, Satir HZ, Ozozan O, et al. Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers. J Foot Ankle Surg 2008; 47:515.
  81. Kessler L, Bilbault P, Ortéga F, et al. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes Care 2003; 26:2378.
  82. Abidia A, Laden G, Kuhan G, et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. Eur J Vasc Endovasc Surg 2003; 25:513.
  83. Doctor N, Pandya S, Supe A. Hyperbaric oxygen therapy in diabetic foot. J Postgrad Med 1992; 38:112.
  84. Lin, TF, Chen, et al. The vascular effects of hyperbaric oxygen therapy in treatment of early diabetic foot. Undersea Hyperb Med 2001; 28(suppl):63.
  85. Hammarlund C, Sundberg T. Hyperbaric oxygen reduced size of chronic leg ulcers: a randomized double-blind study. Plast Reconstr Surg 1994; 93:829.
  86. Löndahl M, Katzman P, Nilsson A, Hammarlund C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care 2010; 33:998.
  87. Zamboni WA, Wong HP, Stephenson LL, Pfeifer MA. Evaluation of hyperbaric oxygen for diabetic wounds: a prospective study. Undersea Hyperb Med 1997; 24:175.
  88. Baroni G, Porro T, Faglia E, et al. Hyperbaric oxygen in diabetic gangrene treatment. Diabetes Care 1987; 10:81.
  89. Tchanque-Fossuo CN, Ho D, Dahle SE, et al. A systematic review of low-level light therapy for treatment of diabetic foot ulcer. Wound Repair Regen 2016; 24:418.
  90. Kajagar BM, Godhi AS, Pandit A, Khatri S. Efficacy of low level laser therapy on wound healing in patients with chronic diabetic foot ulcers-a randomised control trial. Indian J Surg 2012; 74:359.
  91. Kaviani A, Djavid GE, Ataie-Fashtami L, et al. A randomized clinical trial on the effect of low-level laser therapy on chronic diabetic foot wound healing: a preliminary report. Photomed Laser Surg 2011; 29:109.
  92. Landau Z, Migdal M, Lipovsky A, Lubart R. Visible light-induced healing of diabetic or venous foot ulcers: a placebo-controlled double-blind study. Photomed Laser Surg 2011; 29:399.
  93. Minatel DG, Frade MA, França SC, Enwemeka CS. Phototherapy promotes healing of chronic diabetic leg ulcers that failed to respond to other therapies. Lasers Surg Med 2009; 41:433.
  94. Spencer S. Pressure relieving interventions for preventing and treating diabetic foot ulcers. Cochrane Database Syst Rev 2000; :CD002302.
  95. Lewis J, Lipp A. Pressure-relieving interventions for treating diabetic foot ulcers. Cochrane Database Syst Rev 2013; :CD002302.
  96. Lavery LA, Vela SA, Lavery DC, Quebedeaux TL. Total contact casts: pressure reduction at ulcer sites and the effect on the contralateral foot. Arch Phys Med Rehabil 1997; 78:1268.
  97. Mueller MJ, Diamond JE, Sinacore DR, et al. Total contact casting in treatment of diabetic plantar ulcers. Controlled clinical trial. Diabetes Care 1989; 12:384.
  98. Caravaggi C, Faglia E, De Giglio R, et al. Effectiveness and safety of a nonremovable fiberglass off-bearing cast versus a therapeutic shoe in the treatment of neuropathic foot ulcers: a randomized study. Diabetes Care 2000; 23:1746.
  99. Armstrong DG, Nguyen HC, Lavery LA, et al. Off-loading the diabetic foot wound: a randomized clinical trial. Diabetes Care 2001; 24:1019.
  100. Nabuurs-Franssen MH, Huijberts MS, Sleegers R, Schaper NC. Casting of recurrent diabetic foot ulcers: effective and safe? Diabetes Care 2005; 28:1493.
  101. 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; 30:586.
  102. Katz IA, Harlan A, Miranda-Palma B, et al. A randomized trial of two irremovable off-loading devices in the management of plantar neuropathic diabetic foot ulcers. Diabetes Care 2005; 28:555.
  103. Piaggesi A, Viacava P, Rizzo L, et al. Semiquantitative analysis of the histopathological features of the neuropathic foot ulcer: effects of pressure relief. Diabetes Care 2003; 26:3123.
  104. 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.
  105. Armstrong DG, Lavery LA, Kimbriel HR, et al. Activity patterns of patients with diabetic foot ulceration: patients with active ulceration may not adhere to a standard pressure off-loading regimen. Diabetes Care 2003; 26:2595.
  106. Baumhauer JF, Wervey R, McWilliams J, et al. A comparison study of plantar foot pressure in a standardized shoe, total contact cast, and prefabricated pneumatic walking brace. Foot Ankle Int 1997; 18:26.
  107. Pollo FE, Brodsky JW, Crenshaw SJ, Kirksey C. Plantar pressures in fiberglass total contact casts vs. a new diabetic walking boot. Foot Ankle Int 2003; 24:45.
  108. 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; 33:1419.
  109. Reiber GE, Smith DG, Wallace C, et al. Effect of therapeutic footwear on foot reulceration in patients with diabetes: a randomized controlled trial. JAMA 2002; 287:2552.
  110. Ulbrecht JS, Hurley T, Mauger DT, Cavanagh PR. Prevention of recurrent foot ulcers with plantar pressure-based in-shoe orthoses: the CareFUL prevention multicenter randomized controlled trial. Diabetes Care 2014; 37:1982.
  111. IWGDF Guidance on footwear and offloading interventions to prevent and heal foot ulcers in patients with diabetes. http://iwgdf.org/guidelines/guidance-on-footwear-and-offloading-2015/ (Accessed on July 14, 2015).
  112. Brown D, Wertsch JJ, Harris GF, et al. Effect of rocker soles on plantar pressures. Arch Phys Med Rehabil 2004; 85:81.
  113. Busch K, Chantelau E. Effectiveness of a new brand of stock 'diabetic' shoes to protect against diabetic foot ulcer relapse. A prospective cohort study. Diabet Med 2003; 20:665.
  114. Lipsky BA. Medical treatment of diabetic foot infections. Clin Infect Dis 2004; 39 Suppl 2:S104.
  115. Lipsky BA, Pecoraro RE, Larson SA, et al. Outpatient management of uncomplicated lower-extremity infections in diabetic patients. Arch Intern Med 1990; 150:790.
  116. Fowkes FG. The measurement of atherosclerotic peripheral arterial disease in epidemiological surveys. Int J Epidemiol 1988; 17:248.
  117. Faglia E, Clerici G, Clerissi J, et al. Long-term prognosis of diabetic patients with critical limb ischemia: a population-based cohort study. Diabetes Care 2009; 32:822.