Diabetic Foot

Diabetic foot is an umbrella term for foot problems in patients with diabetes mellitus. Due to arterial abnormalities and diabetic neuropathy, as well as a tendency to delayed wound healing, infection or gangrene of the foot is relatively common. Ten to fifteen percent of diabetic patients develop foot ulcers at some point in their lives and foot related problems are responsible for up to 50% of diabetes related hospital admissions.

Diabetic foot ulcer is one of the major complications of Diabetes mellitus. It occurs in 15% of all patients with diabetes and precedes 84% of all lower leg amputations.  Major increase in mortality among diabetic patients, observed over the past 20 years is considered to be due to the development of macro and micro vascular complications, including failure of the wound healing process. Wound healing is a ‘make-up’ phenomenon for the portion of tissue that gets destroyed in any open or closed injury to the skin. Being a natural phenomenon, wound healing is usually taken care of by the body’s innate mechanism of action that works reliably most of the time. Key feature of wound healing is stepwise repair of lost extracellular matrix (ECM) that forms largest component of dermal skin layer.  Therefore controlled and accurate rebuilding becomes essential to avoid under or over healing that may lead to various abnormalities. But in some cases, certain disorders or physiological insult disturbs wound healing process that otherwise goes very smoothly in an orderly manner. Diabetes mellitus is one such metabolic disorder that impedes normal steps of wound healing process. Many histopathological studies show prolonged inflammatory phase in diabetic wounds, which causes delay in the formation of mature granulation tissue and a parallel reduction in wound tensile strength.

Non-healing chronic diabetic ulcers are often treated with extracellular matrix replacement therapy. So far, it is a common trend in diabetic foot care domain to use advanced moist wound therapy, bio-engineered tissue or skin substitute, growth factors and negative pressure wound therapy.  No therapy is completely perfect as each type suffers from its own disadvantages. Moist wound therapy is known to promote fibroblast and keratinocyte proliferation and migration, collagen synthesis, early angiogenesis and wound contraction. At present, there are various categories of moist dressings available such as adhesive backing film, silicone coated foam, hydrogels, hydrocolloids etc. Unfortunately, all moist dressings cause fluid retention; most of them require secondary dressing and hence are not the best choice for exudative wounds.  To address the physiological deficiencies underlying diabetic ulcer, various tissue engineering technologies have come up with cellular as well as acellular skin replacement products.

Prevention is by frequent chiropody review, good foot hygiene, diabetic socks and shoes, and avoiding injury.

• Foot-care education combined with increased surveillance can reduce the incidence of serious foot lesions.

• Footwear.

All major reviews recommend special footwear for patients with a prior ulcer or with foot deformities. One review added neuropathy as an indication for special footwear. The comparison of custom shoes versus well-chosen and well-fitted athletic shoes is not clear.

A meta-analysis by the Cochrane Collaboration concluded that “there is very limited evidence of the effectiveness of therapeutic shoes” . The date of the literature search for this review is not clear. Clinical Evidence reviewed the topic and concluded “Individuals with significant foot deformities should be considered for referral and assessment for customised shoes that can accommodate the altered foot anatomy. In the absence of significant deformities, high quality well fitting non-prescription footwear seems to be a reasonable option”. National Institute for Health and Clinical Excellence has reviewed the topic and concluded that for patients at “high risk of foot ulcers (neuropathy or absent pulses plus deformity or skin changes or previous ulcer” that “specialist footwear and insoles” should be provided.

The one randomized controlled trial that showed benefit of custom foot wear was in patients with a prior foot ulceration. In this trial, the number needed to treat was 4 patients.

Risk factors

Two main risk factors that cause diabetic foot ulcer are Diabetic neuropathy and micro as well as macro ischemia.  Diabetic patients often suffer from diabetic neuropathy due to several metabolic and neurovascular factors. Type of neuropathy called peripheral neuropathy causes loss of pain or feeling in the toes, feet, legs and arms due to distal nerve damage and low blood flow. Blisters and sores appear on numb areas of the feet and legs such as metatarso-phalangeal joints, heel region and as a result pressure or injury goes unnoticed and eventually become portal of entry for bacteria and infection.

Treatment of Foot ulcers in diabetes require multidisciplinary assessment, usually by diabetes specialists and surgeons. Treatment consists of appropriate bandages, antibiotics (against staphylococcus, streptococcus and anaerobe strains), debridement and arterial revascularisation.

It is often 500 mg to 1000 mg of flucloxacillin, 1 g of amoxicillin and also metronidazole to tackle the putrid smelling bacteria.

Specialists are investigating the role of nitric oxide in diabetic wound healing. Nitric oxide is a powerful vasodilator, which helps to bring nutrients to the oxygen deficient wound beds. Specialists are using forms of light therapy, such as LLLT (Low level laser therapy) to treat diabetic ulcers.

In 2004, The Cochrane review panel concluded that for people with diabetic foot ulcers, hyperbaric oxygen therapy reduced the risk of amputation and may improve the healing at 1 year.  They also suggest that the availability of hyperbaric facilities and economic evaluations should be interpreted.

Cellular wound matrices

These type of matrices are used as dermal or both dermal-epidermal substitutes. They are made up of In vitro cultured fibroblasts or keratinocytes onto a biomaterial mesh. As cells proliferate across the mesh, they secrete human dermal collagen, matrix proteins, growth factors and cytokines to create three-dimensional human dermal substitute containing metabolically active living cells. Thus by restoring the dermal tissue, they cause patient’s own epithelial cells to migrate and close the wound.  Unlike dermal substitutes, dermal-epidermal substitutes have a combined dermal and epidermal layer. The epidermal layer is composed of live, differentiating keratinocytes, while the dermal layer consists of living fibroblasts.

Acellular wound matrices

Along the same line, some diabetic wounds may be treated by application of natural or synthetic acellular wound matrices that act as a scaffold at the tissue site to promote fibroblast and keratinocyte migration, to assist in wound closure and thus provide an optimal environment for a restoration of tissue structure and function. These matrices come in different forms. 1. sterile peel open packages for one time use only: In this form, matrix is formulated in the form of a sheet, which has to be cut in a size larger than the outline of wound area either in a dry state or in rehydrated state. 2. Flowable Soft tissue Scaffold: Sometimes, even after surface portion of wound has healed, a remaining tunnel that left treated can lead to breakdown of the wound and formation of new ulcer with easy access to bacteria to cause potentially deep infection.  Therefore, this matrix form is made to be applied with a syringe into tunnels or extensions in case of deep wounds. 3. Bilayer matrix wound dressing: This is a tissue engineered porous matrix of cross-linked bovine tendon collagen and glycosaminoglycan and a semi permeable polysiloxane (silicone) layer. Semi permeable silicone membrane controls water vapor loss, provides a flexible adherent covering for the wound surface and adds tear strength to the device. Moreover, the collagen-glycosaminoglycan biodegradable matrix provides a scaffold for cellular invasion and capillary growth. Wound closure is typically complete within 30 days.

Negative pressure wound therapy

This treatment uses vacuum to remove excess fluid and cellular waste that usually prolong the inflammatory phase of wound healing. In spite of very straightforward mechanism of action, there are lots of inconsistent results of negative pressure wound therapy studies. Research needs to be carried out to optimize the parameters of pressure intensity, treatment intervals and exact timing to start negative pressure therapy in the course of chronic wound healing.

Application of growth factors

This treatment strategy consists of use of growth factors either as one of the components in matrix therapy or via topical application of formulation containing required growth factors. Research shows that growth factors such as epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factor beta (TGF-?), vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) accelerate tissue repair in an experimental wound model. They attach to cell receptors regulating gene expression of several cytokines and chemokines via different signaling pathways. They promote cell division, migration, angiogenesis and thus start tissue regeneration and remodeling process.

Wikipedia