EUROPEAN  TISSUE  REPAIR  SOCIETY

DIALEX – The DIAbetes Lower EXtremity Research Group
E.A. Knowles and A.J.M. Boulton, Manchester Royal Infirmary, UK

THE PROBLEM
It has been estimated that about 15% of the 150 million people in the world with diabetes will develop a foot ulcer at sometime during their life.¹ Foot problems affect people with diabetes globally but with the lack of podiatry and specialist nurses in some countries, many patients still do not have the appropriate care.²

THE MANCHESTER DIABETES FOOT SERVICE
Over the last decade there has been an increased interest in the care of the diabetic foot and many centres in the UK have now established their own foot care teams. Expertise in diabetic foot care has improved and many former research fellows from this unit have subsequently established their own clinics in various UK centres. Our clinic was established in 1987³ and was the first diabetic foot clinic in the North West of England. The clinic and the team have grown in size since then and what was once a ‘Cinderella’ subject has become a speciality. Over fifty patients are seen each week in our foot ulcer clinic, and our high-risk patients are seen in our diabetes centre and community clinics for preventative treatment and foot care education. Our multidisciplinary team includes podiatrists, specialist nurses, doctors, scientists and an orthotist, whose individual skills and knowledge help to build a framework for care.⁴ Patients are referred to other specialist practitioners including vascular and orthopaedic surgeons for investigations and surgery. This team approach has brought together practitioners who were previously working in isolation for the benefit of our most important team member, the patient

Diabetic foot problems can be expensive and time consuming to treat, and a trivial injury if not adequately treated could end in a major amputation. Minor trauma, neuropathy and deformity are the most frequent component cause of diabetic foot ulceration.⁵

Diabetes affects the somatic and autonomic nervous system and can cause a loss of sensation, an alteration in foot shape and a build up of callus under high-pressure areas. A patient with a foot ulcer and an insensitive foot will feel no pain and may continue to weight bear and cause further damage.

Pressure relief, callus debridement, control of infection and the adequacy of the blood supply are assessed in order to successfully treat a foot ulcer. Callus is debrided with a scalpel to prevent further damage and encourage ulcer healing. The larvae of the green bottle fly (Lucilia sericata) are also used to debride sloughy wounds of both inpatients and outpatients. The maggots feed on devitalised tissue and grow rapidly in size and promote rapid cleansing of necrotic and sloughy tissue.⁶

Casts are used to provide pressure relief for foot ulcers. The Scotchcast boot is a well-padded fibreglass cast that has been used in our clinic since 1998.⁷ Casts enable the patient to be ambulant while their ulcers heal and have reduced the number and duration of hospital admissions for foot ulceration. When the ulcers have healed patients are gradually weaned out of their cast and into extra-depth or bespoke shoes with cushioned insoles.

RECENT RESEARCH FROM DIALEX
Our team has participated in many research projects, published articles and presented their research at conferences worldwide. In 1996 we achieved second place in the Journal of Wound Care awards⁴ and in 1999 were runners up in the Hospital Doctor Team of the Year Award.

Bony prominences are particularly susceptible to ulceration and many of our neuropathic patients have prominent metatarsal heads. The fatty pads under the ball of the foot can thin and move forward causing a loss of the natural cushioning making the foot more vulnerable to ulceration. A novel method of replacing this is the injection of small amounts of liquid silicone under the vulnerable areas of the foot.⁸ In a randomised controlled study twenty-eight patients with neuropathy patients were injected with either liquid silicone or saline (placebo group). Barefoot measurements were made of the pressures and tissue thickness of the plantar pads and patients were followed up every three months for a year. Patients who had the silicone injections had a significantly increased thickness of plantar tissue and less callus formation compared to the placebo group.

Surgical resection of the metatarsal heads can also help to restore the foot to a more normal shape and reduce high-pressure areas. We are currently following up patients who have had this type of surgery to determine the benefits and drawbacks of this treatment.

Our optical pedobarograph (foot pressure system) measures plantar foot pressures and identifies areas of high pressures. A more portable foot pressure system is Podotrack; a semi-quantitative plantar pressure measuring device that has been shown by our team to be as effective as the optical pedobarograph providing the observers are trained.⁹

Infections in the diabetic foot are caused by a variety of microrganisms and consequently many doctors prescribe broad-spectrum antibiotics. The over use of antibiotics is leading to the emergence of resistant organisms such as Methicillin Resistant Staphylococcus Aureus (MRSA). A retrospective study showed that ulcers that are infected with MRSA take longer to heal.¹⁰

Our team is active in the treatment of patients with neuropathy and end-stage complications of diabetes. The unrelenting pain of neuropathy causes sleep deprivation and a decreased quality of life. The drugs that are used to alleviate symptoms can have side effects.¹¹ Acupuncture has relieved painful symptoms in about 70% of our patients¹² thus reducing the need for medication.

Morphological aspects of neuropathy are important in planning new treatments. Malik has worked closely with basic scientists to further this research.

The enzymes nitric oxide synthase and arginase in the metabolism of L-arganine (an amino acid involved in wound healing) may be responsible for the impaired wound healing of diabetic foot ulcers. Increased nitric oxide synthase and the increased activity of arginase could account for the callus formation around the neuropathic ulcer. Raised concentrations of nitric acid correlates with the lower concentration of transforming growth factor beta 1.¹³ There is also a lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and foot ulcers.¹⁴

We also collaborate with Prof Mark Ferguson at the Manchester University Medical School and Jude and Oyibo are looking at wound healing in acute and chronic wounds

The study of the psychological effects of foot problems has enabled us to understand the effect of a foot problem on the behaviour of our patients.^15,16 Our group has been working closely with psychologists and patients with neuropathy and our researcher Vileikyte is supported in this important work by a grant from the American Diabetes Association and Diabetes UK. We are working in collaboration with John Hopkins and Penn State Medical schools in the USA.

We liase with other diabetic foot teams in the UK and abroad including Kings College Hospital, London, Nottingham and Edinburgh. Connections are also established with centres in the USA and Lithuania.

The very popular diabetic foot conference in Malvern, UK which is held biennially was originally established by Connor and Boulton. Details of the next conference (May 2002) can be obtained from Anne Roscoe, conference organiser (E-mail: anne.roscoe@man.ac.uk). The diabetic foot study group of the European Association for the Study of Diabetes (EASD) meets regularly, and the UK is hosting this years meeting in Crieffe, Scotland which is also organised by Anne Roscoe (dates 7–9 September 2001, e-mail as above). The Dialex group has an active website:

www.TheDiabeticFoot.net

Our foot care team work hard to prevent and treat foot problems and are active in many diverse areas of research related to the diabetic foot.

References:

1. King H, Aubert RE, Herman WH. Global burden of diabetes 1995–2025: prevalence, numerical estimates and projections. Diabetes Care 1998; 21: 1414–1431.
2. Boulton AJM. The diabetic foot: a global view. Diabetes / Metabolism Research and Reviews. 2000; 16 (suppl 1): S2–S5.
3. Knowles EA, Gem J, Boulton AJM. The diabetic foot and the role of a multidisciplinary clinic. J of Wound Care. 1996; 5: 452–475.
4. Thompson FJ, Veves A, Ashe H, Boulton AJM et al, A team approach to diabetic foot care: the Manchester experience. The Foot 1991; 1: 75–82.
5. Reiber GE, Vilekyte L, Boyko EJ, Del Aguila M, Smith DG, Lavery LA, Boulton AJM. Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes Care 1999; 22: 157–162.
6. Thomas S, Jones M, Shutler S, Jones S. Using larvae in modern wound management J of Wound Care; 1996; 5: 60–9.
7. Knowles EA and Boulton AJM. Use of the Scotchcast boot to heal diabetic foot ulcers. Proceedings of the 5th European Conference on Advances in Wound Management. 1996; 199–201.
8. van Schie CHM, Whalley A, Vileikyte L, Wignall T, Hollis S, Boulton AJM. Efficacy of injected liquid silicone in the diabetic foot to reduce risk factors for ulceration. Diabetes Care 2000; 23: 634–638.
9. van Schie CHM, Abbot CA, Vileikyte L, Shaw JE, Hollis S, Boulton AJM. A comparative study of the Podotrack, a simple semiquantitative plantar pressure measuring device, and the optical pedobaro-graph in the assessment of pressures under the diabetic foot. Diabetic Medicine 1999; 16: 154–159.
10. Tentolouris N, Jude EB, Smirnof I, Knowles EA, Boulton AJM Methicillin-resistant staphylococcus aureus: an increasing problem in a diabetic foot clinic. Diabetic Medicine 1999; 16: 767–771.
11. Boulton AJM. Clinical management of the painful diabetic neuropathies. J of the Royal College of Physicians of London. 2000; 34: 340–343.
12. Abuaisha BB, Constanzi JB, Boulton AJM. Acupuncture for the treatment of chronic painful neuropathy: a long-term study: Diabetes Research and Clinical Practice 1998; 39: 115–121.
13. Jude EB, Boulton AJM, Ferguson MWJ, Appleton I. The role of nitric oxide synthase isoforms and arginase in the pathogenesis of diabetic foot ulcers: possible modulatory effects by transforming growth factor beta 1. Diabetologia 1999 42: 748–757.
14. Blakytny R, Jude EB, Gibson JM, Boulton AJM, Ferguson MWJ. Lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers. J of Pathology. 2000; 190: 589–594.
15. Vileikyte L Psychological and behavioural issues in diabetic neuropathy. In Boulton AJM, Connor H, Cavanagh P (eds), The Foot in Diabetes. 3rd edition  John Wiley & sons Ltd, Chichester, 2000; 121–130.
16. Vileikyte L Psychological aspects of diabetic peripheral neuropathy. Diabetes Review 1999;7: 387–394.

Correspondence to:

Mrs A Knowles
Diabetes Nurse, Manchester Diabetes Centre,
130 Hathersage Road, Manchester M13 0HZ
Tel: 0161 276 6703
Fax: 0161 276 6849
Email: AKnowles@DC.CMHT.NWEST.NHS.UK