Diabetic Foot (Diabetic Ulcer)

Many complications affecting diabetic patients are no more devastating, both psychologically and economically, than limb gangrene and the resulting risk of major limb amputation. The pathophysiology of diabetic foot ulceration is multifaceted.

Pathophysiology

In metabolic and biomechanical pathogenesis, the most characteristic metabolic feature in Type I and Type II diabetes is hyperglycemia. Hyperglycemia exerts its damaging effects on tissues through the following four pathways:

Polyol pathway; glucose is reduced to sorbitol by the aldose-reductase enzyme. The accumulation of sorbitol within the cell increases the osmotic load and leads to irreversible cell damage.
Diacylglycerol-protein kinase c pathway; Protein kinase c is the only enzyme activated within the cell. Activation of this enzyme leads to structural changes in the vascular structure, especially in the lumen. Non-enzymatic glycosylation; Excessive glycosylation occurs as a result of covalent binding of aldoses with reactive amino groups. Increased protein catabolism; Negative protein balance negatively affects the healing process.

Neuropathy

Peripheral neuropathy, involving motor, sensory, and autonomic pathways, is the primary abnormality causing plantar ulceration in diabetic patients. Endoneural edema and slow axoplasmic flow play a role in nerve dysfunction, referred to as “diabetic peripheral neuropathy.”

Vascular Disease

Peripheral vascular disease may play a role in the persistence of diabetic foot ulceration in some patients, but it is clearly not the primary etiological factor. In many diabetic patients, disease develops within the tibioperoneal trunk without affecting pedal circulation. This “pedal protection” is an important concept and is the reason for excellent results in bypass graft surgery of the ankle or foot dorsum. Adequate arterial flow ensures successful wound closure in these patients.

Hemorheology

Blood flow in diabetic patients changes due to increases in blood viscosity and abnormalities in erythrocyte deformability. Among the various factors causing high blood viscosity, platelet aggregation, erythrocyte aggregation, and increased fibrinogen levels are well-documented in diabetic patients and are the cause of many changes.

Immunology

Diabetic patients exhibit both cell-mediated and humoral-mediated types of immune system dysfunction. A small fissure on the plantar surface of the diabetic foot provides entry for bacteria. Functional deformities of polymorphonuclear neutrophil leukocytes (PMNs) in these patients facilitate the resulting foot infections.

Biomechanics

Approximately 35% of diabetic patients show significant signs of peripheral neuropathy, many of whom have gait abnormalities. The most serious manifestation of this neuropathic condition is Charcot foot. The most widely accepted explanation for these degenerative changes is neurotraumatic.

Preoperative Evaluation

1. Systemic Evaluation

Many of these patients also have coronary, cerebrovascular, pulmonary, and renal disease. Every effort should be made to systematically optimize the patient’s condition before initiating surgical reconstruction. Poor glucose control, characterized by high serum hemoglobin A1c levels, should be corrected to improve associated hemorrhagic and immunological abnormalities.

2. Radiological Analysis

Plain bone radiographs should be obtained before planning any intervention on the foot. High-resolution 3D imaging techniques can provide significant information about abnormal bone anatomy. After film evaluation, nuclear scans are performed on most patients, which is a misleading and unnecessary procedure. These studies are usually positive at the ankle, midfoot, and forefoot levels in diabetic patients without associated foot ulceration. Neuroarthropathy in these patients often results in false positive scans.
Bone biopsy is essential before deciding on long-term IV antibiotic therapy, regardless of the radiological method used to diagnose osteomyelitis.

3. Vascular Assessment

Vascular studies begin with a careful physical examination of atrophic skin changes associated with chronic ischemia and indurated skin discoloration resulting from long-term vascular insufficiency. Palpation of the pedal pulses provides a qualitative assessment of blood flow, but quantitative assessment can be obtained through ankle-brachial index and Doppler waveform measurements.

Transcutaneous oxygen pressure measurements are among the reliable methods. Normally, TcPO is around 80% of arterial oxygen pressure and is usually above 55 mmHg. Wound healing is impaired when this value falls below 20-30 mmHg.

4. Neurological Assessment

Careful medical evaluation of sensory and motor deficits in diabetic patients should be completed before any reconstructive procedure. If partial sensory loss is limited in the ulceration area, the surgeon can create a reconstructive plan that includes the transfer of sensory tissue during soft tissue reconstruction.

In neurological examination, sensory evaluation of the foot is important. The most commonly used method is evaluation with ‘Semmes-Weinstein monofilaments’. If there is multiple nerve compression in the tarsal canal region, percussion of the posterior tibial nerve in this region usually yields the Tinel sign. The same applies to the peroneal nerve in the proximal calf (fibula head region).

5. Gait Analysis

Most candidates undergoing soft tissue repair have gait abnormalities. Midfoot and forefoot ulceration occur with increased weight-bearing in these areas during ambulation and often with Achilles tendon shortening. Preoperative gait evaluation should include measurement of ankle dorsiflexion and computerized gait analysis.
The first step in evaluating a diabetic wound is determining its depth. The Wagner classification is widely accepted in the evaluation of diabetic wounds.

Table 1. Wagner Classification
Grade Description
0. Skin intact but bone deformities that may cause ulceration
I. Localized superficial ulcer
II. Deep ulcer reaching bone, tendon, ligament, joint
III. Deep abscess, osteomyelitis
IV. Gangrene in the forefoot or toes
V. Gangrene throughout the foot

Ischemic ulcers: The most common symptom in diabetics with circulatory problems is painful and non-healing ulcers that develop in a short period of time. Physical examination findings include decreased or absent foot pulses, pallor in the foot, slowed venous filling after elevation of the foot, and hair loss. Sensory loss due to neuropathy may mask the pain associated with ischemic disease.

Neuropathic ulcers: The classic “trophic” or “mal perforations” ulcers seen in diabetic patients are ulcers that develop on a neuropathic basis. Neuropathic ulcers are characteristically ulcers with thick edges, thick and coarsened surrounding skin, little necrotic tissue, and abundant granulation tissue. They are painless and can persist for years. There is usually an underlying deformity causing the ulcer.

Treatment

Growth factors are administered to the wound as platelet products, bioengineered products (cultured cells or composite skin), or recombinant growth factors. Another natural source of growth factors is cultured cells and bioengineered tissues. The first cells tested were cultured keratinocytes. Preliminary and uncontrolled studies have shown that keratinocytes are useful in treating all chronic dermal wounds. The most important criterion for an ideal skin equivalent is the functional and structural similarity expected from an autograft. Products used for immediate and permanent wound closure are examined in three main groups. Class I products contain only cultured epidermal equivalents. Class II skin equivalents consist of dermal components containing collagen and other matrix proteins obtained by processing or synthetically producing skin. Class III skin equivalents contain completely separate dermal and epidermal components and can be called composite skin. Both keratinocytes and fibroblasts produce different cytokines and growth factors. The combination of the two cell types leads to a synergistic increase in growth factor production. Another treatment option for diabetic foot ulcers is recombinant growth factors. Regranex, a recombinant PDGF, is FDA-approved for the treatment of chronic diabetic foot ulcers.

Surgical Techniques

The surgical plan should ensure stable wound closure using the simplest technique available. Skin grafting, local flaps, limited amputations, midfoot amputations, regional flaps, and free tissue transfer procedures should be in the reconstructive surgeon’s equipment. In patients with ulcers in the forefoot, limited toe or rail amputation or more aggressive transmetatarsal or Lisfranc amputation provides the best functional outcome compared to complex microvascular reconstruction.

However, despite the increasing number of both pedicled and free flaps, patient characteristics influence the choice of wound closure.
Recently, the use of vacuum-assisted closure techniques has greatly simplified pressure ulcer closure procedures (especially in frail patients who are candidates for amputation). If the wounds are large or not suitable or safe for local flaps, free tissue transfer is required. Recent publications have shown that some patients benefit from a combination of lower extremity bypass or free flap reconstruction. Bone and tendon abnormalities should be identified beforehand to prevent recurrent ulcerations. The reconstructive plastic surgeon should collaborate with an orthopedist or podiatrist who is interested in and skilled in diabetic biomechanical abnormalities. In some patients, tendon lengthening, tendon transfer, osteectomy, osteotomy, joint fusion, or midfoot fusion may be necessary to ensure a complication-free recovery period.