Many complications affecting patients with diabetes are not more devastating, both psychologically and economically, than limb gangrene and the associated risk of major limb amputation. There are many factors in the pathophysiology of diabetic foot ulceration.

Pathophysiology

In the metabolic and biomechanical pathogenesis, the most characteristic metabolic feature in Type I and Type II diabetes is hyperglycemia. Hyperglycemia shows its damaging effect on tissues in the following four ways. These;

a) the polyol pathway; glucose is reduced to sorbitol by the enzyme aldose-reductase. Accumulation of sorbitol in the cell increases the osmotic load and leads to irreversible cell damage.
b) Diacylglycerol-protein kinase c pathway; Protein kinase c is the only enzyme activated inside the cell. With the activation of this enzyme, structural changes occur in the vessel structure and especially in the lumen.
c) Nonenzymatic glycosylation; Excessive glycosylation occurs as a result of covalent binding of aldoses with reactive amino groups.
d) Increased protein catabolism; Negative protein balance negatively affects the healing process.

Neuropathy

Peripheral neuropathy, which includes motor, sensory and autonomic pathways, is the main abnormality that causes plantar ulceration in patients with diabetes. Endoneural edema and slow axoplasmic flow play a role in nerve dysfunction called “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 clear that it is not of primary etiological interest. In many diabetic patients, the disease occurs in the tibioperoneal trunk without affecting the pedal circulation. This “pedal protection” is an important concept and is the reason for the excellent results in bypass graft surgery of the ankle or dorsum of the foot. Adequate arterial flow is to ensure successful closure of wounds in these patients.

Hemorheology

The blood flow of patients with diabetes varies due to elevations in blood viscosity and abnormalities in erythrocyte deformability. Among the various factors that cause 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

Both cell-mediated and humoral-mediated types of immune system dysfunction are seen in patients with diabetes. A small fissure on the plantar surface of the diabetic foot provides entry for bacteria. In these patients, functional deformations of polymorphonuclear neutrophil leukocytes (PMNs) facilitate foot infections resulting from this.

Biomechanics

Up to 35% of patients with diabetes show significant signs of peripheral neuropathy, and most of them have gait abnormalities. The most serious manifestation of this neuropathic condition is Charcot foot. The most accepted explanation for these degenerative changes is neurotraumatic.
Preoperative evaluation

1. Systemic Evaluation

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

2. Radiological Analysis

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

3. Vascular Evaluation

Vascular studies begin with careful physical examination of atrophic skin changes associated with chronic ischemia and indurated skin discoloration with prolonged vascular insufficiency. Palpation of the pedal pulses provides a qualitative assessment of blood flow, but quantitative assessment can be obtained by measurements of the ankle–brachial index and Doppler waveforms. Transcutaneous oxygen pressure measurements are among the reliable methods. Normally, TcPO is around 80% of arterial oxygen pressure and is usually above 55 mmHg. In cases where this value falls below 20-30 mmHg, wound healing is impaired.

4. Neurological Evaluation

Careful medical evaluation of sensory and motor deficits in patients with diabetes should be completed prior to any reconstructive procedure. If partial sensory loss at the ulcer site is limited, the surgeon can create a reconstructive plan that includes the transfer of sensory tissue during soft tissue reconstruction. Sensory evaluation of the foot is important in the neurological examination. The most commonly used method is the evaluation with ‘Semmes-Weinstein monofilaments’. If multiple nerve compression has occurred in the tarsal canal region, the Tinel sign is usually obtained by percussion of the posterior tibial nerve in this region. The same is true for the peroneal nerve in the proximal calf (fibular head region).

5. Gait Analysis

Most candidates for soft tissue repair have gait abnormalities. Midfoot and forefoot ulceration occurs with more weight being placed on these areas during ambulation and usually with shortening of the Achilles tendon. Preoperative assessment of gait should include measurement of wrist dorsiflexion and computerized gait analysis.
The first step in the evaluation of a diabetic wound is to determine the depth of the wound. The Wagner classification is widely accepted in the evaluation of diabetic wound.

Wagner classification

Degree Description

0. The skin is intact but there are bony deformities that may cause scarring
I. Localized superficial ulcer
II. Deep ulcer reaching bone, tendon, ligament, joint
III. Deep abscess, osteomyelitis
IV. Gangrene of the forefoot or toes
V. Whole foot gangrene

Ischemic ulcers: The most common symptom in diabetics with circulatory disorders is painful and non-healing ulcers that occur in a short time. Decreased or inability to get foot pulses, paleness in the foot, slowing of venous filling after raising the foot, and hair loss are physical examination findings. Loss of sensation due to neuropathy may mask the pain associated with ischemic disease.

Neuropathic ulcers: Classical “trophic” or “mal perforating” ulcers seen in diabetic patients are ulcers formed on a neuropathic basis. Neuropathic ulcers are characteristic ulcers with thick margins, thick and coarse surrounding skin, less necrotic tissue, and excess granulation tissue. They are painless and can persist for years. Often there is a deformity that causes an ulcer.

Treatment

Growth factors have been given 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 to be tested were cultured keratinocytes. In preliminary and uncontrolled studies, they said that keratinocytes are useful in the treatment of 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 are composed of dermal components including collagen and other matrix proteins obtained by processing or synthetically producing leather. 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 in the treatment of diabetic foot ulcers is recombinant growth factors. Regranex, a recombinant PDGF, has been approved by the FDA 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 equipment of the reconstructive surgeon. In patients with anterior foot wounds, limited toe or rail or more aggressive transmetatarsal or lisfranc amputation provides the best functional outcome over complex microvascular reconstruction.

However, despite the increase in the number of both pedicled and free flaps, the patient’s characteristics affect the choice of wound closure.

The recent use of vacuum-assisted closure techniques has greatly simplified pressure ulcer closure procedures (especially in debilitated patients who are somewhat amputated). If wounds are large or unsuitable or unsafe for local flaps, free tissue transfer is required. Recent publications have shown that some patients benefit from the combination of lower extremity by-pass or free flap reconstruction. Bone and tendon abnormalities should be identified beforehand to prevent recurrent ulcerations. The reconstructive plastic surgeon should cooperate with an orthopedist or podiatrist who is interested and skilled in diabetic biomechanical abnormalities. It may be necessary for some patients to undergo tendon lengthening, tendon transfer, ostectomy, osteotomy, joint fusion or midfoot fusion in order to have a complication-free period in the future.