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Keywords:

  • diabetic foot;
  • diabetic neuropathy;
  • ulceration;
  • amputation;
  • epidemiology;
  • pathogenesis

Abstract

  1. Top of page
  2. Abstract
  3. Grand overview
  4. Epidemiology
  5. Pathogenesis of diabetic foot ulceration
  6. Conflict of interest
  7. References

This review assesses the progress that has been made over the last quarter century in our understanding of the pathogenesis of diabetic foot problems as well as in their management. Some recent exciting developments are highlighted. This is followed by a brief discussion on the epidemiology and causal pathways to diabetic foot disease. Copyright © 2008 John Wiley & Sons, Ltd.

‘Superior doctors prevent the disease.

Mediocre doctors treat the disease before evident.

Inferior doctors treat the full-blown disease’.

Huang Dee, China, B.C. 2600

In this article, as part of the grand overview, I will review what progress has been made in diabetic foot care in the last two to three decades, will consider where we are now and suggest where we might go so that we, as the Chinese proverb states, might become ‘superior doctors in preventing the disease’. Finally a brief consideration of the current epidemiology and pathogenesis of diabetic foot ulcers will conclude this article.

Grand overview

  1. Top of page
  2. Abstract
  3. Grand overview
  4. Epidemiology
  5. Pathogenesis of diabetic foot ulceration
  6. Conflict of interest
  7. References

Where have we come from?

The Chinese proverb suggests that inferior doctors treat the full-blown disease, and until recent years, this was sadly the case with diabetic foot disease. As reviewed elsewhere in this issue by Connor 1, although the existence of foot problems and their relationship with diabetes was recognized in the 19th century, little progress was made in the management of diabetic foot ulcers in the first half of the 20th century. Thus patients often presented late and in many cases the first treatment was a major amputation. Sadly, in some parts of the world this is still true today 2. In the Caribbean, for example, where the diabetes prevalence is 10–20% in many islands, the number of amputations in diabetic patients is among the highest in the world 3. An example of this was quoted by Walrond who reported in 2001 that in one hospital in Barbados, patients with diabetic foot lesions occupied 75% of all surgical beds, and that one-third of these ended up with a major amputation 4.

The first real progress in understanding the pathogenesis of foot problems in patients with sensory loss came from work in leprosy 5. Although the cause of sensory loss is very different from that in diabetes, the end result is the same—thus work in leprosy has been very relevant to our understanding of the pathogenesis of diabetic foot lesions. One of the pioneers of research into the causation of foot problems in leprosy was Dr Paul Brand (1914–2003), who worked as a surgeon and a missionary in South India. It was Brand who added science to the art of foot care 6. Although always emphasizing the art of clinical medicine in his work, Brand also performed pioneering research looking at abnormal foot pressures during walking, and he described the use of thermography in assessing areas at the risk of imminent breakdown 7, 8. It was Brand who taught us the principles of management of the insensitive foot, repeatedly emphasizing the need for offloading plantar neuropathic ulcers, which frequently went on to heal even in the days prior to antibiotics. He always emphasized to his students the power of clinical observation and one remark of his that was very relevant to diabetic foot ulceration was that any patient with a plantar ulcer who walks into the clinic without a limp has neuropathy.

Much progress in our understanding of the pathogenesis and management of the diabetic foot has been made over the last quarter century. This has been matched by an increasing number of publications in peer-review journals. Taken as a percentage of all PubMed listed articles on diabetes, those on the diabetic foot have increased from 0.7% in the 1980–88 period to more than 2.7% in the years 1998–2004 6. During this same period of time, there has been an increase in the number of national and international meetings on the diabetic foot, which were virtually unheard of prior to 1980. The first Malvern Diabetic Foot Meeting was organized in the United Kingdom in 1986 and this resulted in one of the early multi-disciplinary team authored books on clinical management of the diabetic foot 9. The Foot Council (now Foot Care Interest Group) of the American Diabetes Association was formed in 1987 and the first international diabetic foot meeting in Noordwijkerhout occurred in 1991. The European Association for the Study of Diabetes founded a study group on Diabetic Foot Disease in 1998 and the first international consensus on diabetic foot care was published in 1999.

Such is the importance of diabetic foot disease across the world that the International Diabetes Federation (IDF) dedicated the year 2005 to Diabetic Foot Care, emphasizing the possibilities of prevention of amputation and raising awareness among the medical and patient community of foot disease in diabetic patients. A main focus of the IDF Year of the Diabetic Foot was that on World Diabetes Day, 14 November 2005, a global press conference was held on diabetic foot disease during the Brazilian Diabetes Meeting in Salvador, Brazil. At the same time, the Lancet, a highly respected general medical journal, virtually dedicated a whole issue to diabetic foot disease that was published to coincide with World Diabetes Day.

Where are we now?

It is clear from reading the previous paragraphs that much progress has indeed been made in our understanding and treatment of diabetic foot disease. The many outstanding contributions in this supplement attest to the marked interest and research activity in diabetic foot disease. The seventh edition of the longstanding Levin and O'Neal's ‘The Diabetic Foot’ has just been published and included the DVD from the International Working Group on Diabetic Foot Disease reports that resulted from the 2007 international meeting on the diabetic foot in The Netherlands 10. The European textbook, ‘The Foot in Diabetes’ is now in its fourth edition 11 and a search on Pubmed for articles published during 2007 on the diabetic foot identified 274 articles, in contrast with the 14 published during the year 1980.

In the recent years, much emphasis has been put upon the team approach to diabetic foot care and there has been increasing evidence of national and international cooperation in this regard. Success stories come from all over the world and include the ‘Save the Diabetic Foot—Brazil’ project, which has seen the establishment of more than 60 diabetic foot clinics across the largest country in South America 12 and the Kyoto Diabetic Foot Group that has helped with education of health care professionals in diabetic foot care in many countries including China, Mongolia, India, Vietnam, Indonesia and Malaysia. Lastly, in Europe, the Eurodiale Consortium has been assessing the optimal organization of health care in diabetic foot disease across Europe 13. Despite all this progress, there are still large gaps in our areas of knowledge that are identified in many of the articles in this supplement. Many treatments (particularly pertaining to dressings, topical applications) lack any evidence from appropriately designed randomized controlled trials, and despite the commonly held belief that education should reduce the incidence of new and recurrent ulcers, there is no good evidence to support, to date, that this is indeed the case. Another area identified in this supplement, as requiring good original randomized controlled trials, is the question of the role of footwear in the prevention of ulcers and the reduction in numbers of recurrent ulcers.

Where are we going?

At the end of the fifth International Symposium on the Diabetic Foot in The Netherlands, May 2007, Professor Peter Cavanagh (Cleveland Clinic, USA) gave his view as to where diabetic foot care might be in 25 years from now. Prior to his presentation, he contacted a number of authorities on the diabetic foot and asked them for their views on this matter. Although it is not possible in this review to go through all the predictions, a few, which have already begun to show signs of success, will be highlighted. Cavanagh divided the experts' predictions into three areas: innovators, policy makers and implementers. First, it was suggested that polymerase chain reaction for the identification of all foot infection samples would become available. A few months after this prediction, Sotto and colleagues from France reported that DNA array appears as a promising technique and is easy to perform and might help distinguish colonized ulcers from infected ones 14. In terms of new therapy, it is clear that stem cells will increasingly play a part in accelerating cutaneous wound healing 15.

Under the title ‘Implementers’ several experts suggested that better organization and health care delivery would improve diabetic foot care. In early 2008, Canavan et al. reported that diabetes-related lower extremity amputations in the North of England reduced over a 5-year period of time during which improvements in the organization of diabetes care were implemented 16.

Epidemiology

  1. Top of page
  2. Abstract
  3. Grand overview
  4. Epidemiology
  5. Pathogenesis of diabetic foot ulceration
  6. Conflict of interest
  7. References

As foot ulceration and amputation are closely inter-related in diabetes 17, they will be considered together in this section especially as > 85% of amputations are preceded by an active foot ulcer. The term ‘diabetic foot’ will be taken to encompass any foot lesion occurring as a result of diabetes and its complications. A selection of epidemiological data for foot ulceration and amputation, originating from studies from a number of different countries, is provided in Table 1. Globally, the diabetic foot remains a major medical, social and economic problem that is seen in every country 17. However, the reported frequencies of amputation and ulceration do vary considerably as a consequence of different diagnostic criteria used as well as regional differences 18. According to Singh et al.19, up to 25% of patients with diabetes will develop a foot ulcer sometime during their lives and, as can be seen from the table, up to 2% of patients may already have undergone amputation. Diabetes remains the major cause of non-traumatic amputation in most western countries; rates are as much as 15 times higher than in the non-diabetic population.

Table 1. Epidemiology of foot ulceration and amputation
 Prevalence (%)Incidence (%)Risk factors
Authors (Ref)CountryYearN  for foot
UlcersAmputationUlcersAmputationulcers (%)
  • a

    Canadian Aboriginal population.

  • b

    Active ulcers.

  • c

    Incidence figures over 3 years.

  • d

    Active ulcers: 5.4% past or currently active ulcers.

  • e

    Incidence figures over 4 years.

Al-Mahroos & Al-Roomi 20Bahrain200714775.945
Reid et al.21Canadaa20061695b3> 42
Abbott et al.22UK200297101.71.32.2> 50
Manes et al.23Greece20028214.8> 50
Muller et al.24Netherlands20026652.10.6
Ramsey et al.25USA199989655.8c0.9c
Vozar et al.26Slovakia199712052.50.90.60.6
Kumar et al.27UK19948211.4d42
Moss et al.28USA1992290010.1e2.1e

Although many of the studies referred to and listed in Table 1 were well conducted, methodological issues remain which make it difficult to do direct comparison between studies/countries. First, definition as to what constitutes a foot ulcer varies and secondly, surveys invariably include only patients with previously diagnosed diabetes, whereas in type 2 diabetes foot problems may be the presenting feature. In one study from the United Kingdom, for example, 15% of patients undergoing amputation were first diagnosed with diabetes on that hospital admission 29. Thirdly, reported foot ulcers are not always confirmed by direct examination by the investigators involved in studies. Finally, as can be seen from the table, in those studies that assessed the percentage of the population that had risk factors for foot ulceration, between 40 and 70% of patients fell into the high-risk category. Such observations clearly indicate the need for all diabetes services to have a regular screening programme to identify such high-risk individuals.

Pathogenesis of diabetic foot ulceration

  1. Top of page
  2. Abstract
  3. Grand overview
  4. Epidemiology
  5. Pathogenesis of diabetic foot ulceration
  6. Conflict of interest
  7. References

It is well recognized that a number of contributory factors working together ultimately result in the final pathway to foot ulceration in diabetic patients. The commonest component causes in this pathway include peripheral neuropathy, foot deformity, external trauma, peripheral vascular disease and peripheral oedema 6. With the exception of trauma, none of the above risk factors will cause ulceration in isolation. A joint UK–US study in 1999 identified that the commonest combination of factors resulting in foot ulceration was peripheral neuropathy, foot deformity and trauma 30.

Ethnicity and gender also have associations with neuropathy. In Western countries, foot ulcers are more common in male patients 22, and in mixed populations, foot ulceration is more common among those of European origin when compared to Asians and African–Caribbeans 31. However, the greatest single risk factor for foot ulceration is a past history of either ulceration or amputation 6.

A recent systematic review and meta-analysis considered the predictive value of diagnostic tests and physical signs in the prediction of foot ulceration 32. This review concluded that a number of diagnostic tests and physical signs that detect neuropathy (e.g. biothesiometry, monofilament screening and absent ankle reflexes) and also those that detect excessive plantar pressure (peak plantar pressures and joint deformities), were significantly associated with future foot ulceration. The fact that symptoms were not found to be a useful predictor of future ulceration in this review, reinforces the message that all patients with diabetes should have their feet examined every time they are seen by a health care professional.

In conclusion, much progress has been made in the last 20 years in our understanding of the pathogenesis and management of diabetic foot problems, and the volume of research activity in this area is rapidly increasing, as evidenced by the many important contributions to this supplement. However, the current ‘epidemic’ of type 2 diabetes that is being witnessed throughout the world is resulting in an ever-increasing population of diabetic patients with lower limb complications. The challenge in the years before the next international meeting is to continue increasing the awareness of diabetic foot problems, their causes and management, across the world, so that, as the Chinese proverb states, we promote those ‘superior’ health care professionals who prevent the disease.

References

  1. Top of page
  2. Abstract
  3. Grand overview
  4. Epidemiology
  5. Pathogenesis of diabetic foot ulceration
  6. Conflict of interest
  7. References
  • 1
    Connor H. Some historical aspects of diabetic foot disease. Diabetes Metab Res 2008; 24(SX): xxxx.
  • 2
    Boulton AJM, Vileikyte L. Diabetic foot problems and their management around the world. In The Diabetic Foot (7th edn), BowkerJH, PfeiferM (eds). Mosby Elsevier: Philadelphia, PA, 2008; 487496.
  • 3
    Gulliford MC, Mahabir D. Diabetic foot disease in a Caribbean community. Diabetes Res Clin Pract 2002; 56: 3540.
  • 4
    Walrond ER. The Caribbean experience with the management of the diabetic foot. West Indian Med J 2001; 50(S1): 2426.
  • 5
    Boulton AJM. Diabetic foot ulceration: the leprosy connection. Pract Diabet Digest 1990; 3: 3537.
  • 6
    Boulton AJM. The diabetic foot: from art to science. Diabetologia 2004; 47: 13431353.
  • 7
    Bauman JH, Brand PW. Measurement of pressure between foot and shoe. Lancet 1963; 1: 629632.
  • 8
    Bergtholdt HT, Brand PW. Temperature assessment and plantar inflammation. Lepr Rev 1976; 47: 211219.
  • 9
    Connor H, Boulton AJM, Ward JD. The Foot in Diabetes (1st edn), John Wiley and Sons: Chichester, 1987; 1168.
  • 10
    Bowker JH, Pfeifer MA. Levin and O'Neal's The Diabetic Foot (7th edn), Mosby Elsevier: Philadelphia, PA, 2008; 1627.
  • 11
    Boulton AJM, Cavanagh PR, Rayman G. The Foot in Diabetes (4th edn), John Wiley and Sons: Chichester, 2006; 1449.
  • 12
    Pedrosa HC, Leme LAP, Novaes C, et al. The diabetic foot in South America: progress with the Brazilian save the diabetic foot project. Int Diabet Monitor 2004; 16(4): 1724.
  • 13
    Prompers L, Huijberts M, Apelqvist J, et al. Optimal organization of health care in diabetic foot disease: introduction to the Eurodiale project. Int J Low Extrem Wounds 2007; 6: 1117.
  • 14
    Sotto A, Richard JL, Jourdan N, et al. Miniaturized oliyonucleotide arrays: a new tool for discriminating colonization from infection due to staphylococcus aureus in diabetic foot ulcers. Diabetes Care 2007; 30: 20512056.
  • 15
    Cha J, Falanga V. Stem cells in cutaneous wound healing. Clin Dermatol 2007; 25: 7378.
  • 16
    Canavan RJ, Unwin NC, Connolly VM, Kelly WF. Diabetes and non-diabetes related lower extremity amputation incidence before and after the introduction of better organized diabetes foot care. Diabetes Care 2008; 31:(in press).
  • 17
    Boulton AJM, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet 2005; 366: 17191724.
  • 18
    van Houtum WH. Amputations and ulceration; pitfalls in assessing incidence. Diabetes Metab Res 2008; 24(SX): xxxx.
  • 19
    Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005; 293: 217228.
  • 20
    Al-Mahroos F, Al-Roomi K. Diabetic neuropathy, foot ulceration, peripheral vascular disease and potential risk factors among patients with diabetes in Bahrain: a nationwide primary care diabetes clinic-based study. Ann Saudi Med 2007; 27: 2531.
  • 21
    Reid KS, Martin BD, Duerksen F, et al. Diabetic foot complications in a northern Canadian Aboriginal community. Foot Ankle Int 2006; 27: 10651073.
  • 22
    Abbott CA, Carrington AL, Ashe H, et al. The North-West Diabetes Foot Care Study: incidence of, and risk factors for new diabetic foot ulceration in a community-based patient cohort. Diabet Med 2002; 19: 377384.
  • 23
    Manes C, Papazoglou N, Sassidou E, et al. Prevalence of diabetic neuropathy and foot ulceration: a population-based study. Wounds 2002; 14: 1115.
  • 24
    Muller IS, de Grauw WJ, van Gerwen WH, et al. Foot ulceration and lower limb amputation in type 2 diabetic patients in Dutch primary health care. Diabetes Care 2002; 25: 570576.
  • 25
    Ramsey SD, Newton K, Blough D, et al. Incidence, outcomes and costs of foot ulcers in patients with diabetes. Diabetes Care 1999; 22: 382387.
  • 26
    Vozar J, Adamka J, Holeczy P, et al. Diabetics with foot lesions and amputations in the region of Horny Zitmy Ostrov 1993–1995. Diabetologia 1997; 40(S1): A46.
  • 27
    Kumar S, Ashe HA, Parnell LN, et al. The prevalence of foot ulceration and its correlates in type 2 diabetic patients: a population–based study. Diabet Med 1994; 11: 480484.
  • 28
    Moss S, Klein R, Klein B. The prevalence and incidence of lower extremity amputation in a diabetic population. Arch Intern Med 1992; 152: 510616.
  • 29
    Deerochanawong C, Home PD, Alberti KG. A survey of lower limb amputations in diabetic patients. Diabet Med 1992; 9: 942946.
  • 30
    Reiber GE, Vileikyte L, Boyko EJ, et al. Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes Care 1999; 22: 157162.
  • 31
    Abbott CA, Garrow AP, Carrington AL, et al. Foot ulcer risk is lower in South-Asian and African-Caribbean compared with European diabetic patients in the UK. Diabetes Care 2005; 28: 18691875.
  • 32
    Crawford F, Inkster M, Kleijnen J, Fahey T. Predicting foot ulcers in patients with diabetes: a systematic review and meta-analysis. Q J Med 2007; 100: 6586.