- Diagnosis and Classification of Diabetes
- Initial Assessment and Criteria for Specialist Referral
- Glycaemic Control in Type 2 Diabetes - Oral Hypoglycaemic Agents
- Indications for Insulin in Type 2 Diabetes
- Hypertension
- Dyslipidaemia
- Aspirin Therapy in Diabetes
- Retinopathy
- Nephropathy
- Neuropathy and Foot Ulcers
- Sexual Dysfunction in Men
- Diabetes in Pregnancy and Pre-conception Guidance
10. Neuropathy and Foot Ulcers
Diabetic foot ulcers are a major cause of morbidity and mortality, accounting for approximately two-thirds of all non-traumatic amputations. A combination of seven problems underlay the need for amputation in all patients: ischaemia, infection, neuropathy, poor wound healing, minor trauma, skin ulceration, and gangrene. A potentially preventable initiating event can be identified in over 80%, most often minor trauma that caused cutaneous injury. This observation illustrates the importance of frequent evaluation of the feet in diabetic patients.
An assessment of the diabetic foot should include:
- Skin integrity especially between the toes and under the metatarsals, thickened skin over pressure areas and fungal infections
- Vascular supply – a history of claudication and the presence of pedal pulses with bruits
- Neuropathy – reduced vibration sense is a good indicator of risk, ankle jerks. Symptoms of numbness and paraesthesia should be sought.
The presence of any of these factors plus a history of previous foot ulcers, increasing age, visual impairment, limited mobility and poor social circumstances indicate a high-risk foot. All patients should receive regular education regarding foot care, but this becomes particularly important once neuropathy has developed. All high-risk patients should also be referred to the podiatrist and advised re cushioned footwear and the importance of not walking barefoot.
There are three elements in the effective treatment of diabetic neuropathy:
- Glycaemic control
- Foot care
- Treatment of pain
Glycaemic Control – The most important treatment for the prevention of diabetic neuropathy is optimal glucose control. In the Diabetes Control and Complications Trial (DCCT), the occurrence of diabetic neuropathy was reduced by 60% over a 10-year period with rigorous blood glucose control in patients with type 1 diabetes mellitus. The role of glycaemic control in established diabetic neuropathy is less established, but several small, mostly uncontrolled studies suggest that neuropathic symptoms may improve with intensive anti-diabetic therapy. In the DCCT, a five-year follow-up in patients with possible or definite clinical neuropathy at baseline showed a benefit of intensive glycaemic control on nerve conduction velocity.
Aldose Reductase Inhibitors – In addition to lowering blood glucose concentrations, another potential approach is to minimise the toxicity of hyperglycaemia. To the degree that sorbitol accumulation might play a role in diabetic neuropathy, use of an aldose reductase inhibitor to prevent sorbitol formation might be beneficial. In the studies reported thus far, there has usually been no improvement in pain, an inconsistent effect on paraesthesias, and an increase in nerve conduction in some but not all nerves.
Angiotensin-Converting Enzyme Inhibitors –ACE inhibitors play a major role in the treatment of hypertension and in the prevention of progression of nephropathy in patients with diabetes. ACE inhibitors presumably act by inhibiting the production of angiotensin II, thereby lowering systemic and intraglomerular pressures. By mechanisms that are less clear, these drugs also may be beneficial in diabetic retinopathy and neuropathy.
Pain Control
Diagnosis – The onset of severe pain in the feet and lower limbs can be very distressing and disabling. A disc lesion should be considered if the pain has developed in relation to recent trauma or its onset is abrupt. In the absence of these features, the differential diagnosis is neuropathy or peripheral vascular disease. The physical examination may be helpful (decreased sensation or loss of deep tendon reflexes) but these signs of neuropathy do not necessarily mean that the pain is due to the neuropathy.
Several clues that the patient has neuropathic pain are the location of pain (feet more than calves), the quality of the pain, and the timing of pain (present at rest, improves with walking). Each of these features is different from those of the pain due to ischemic vascular disease.
Spontaneous resolution – Once the diagnosis of painful diabetic neuropathy is established, the patient should be reassured that the condition is usually self-limiting. Remission is more likely if the onset of symptoms follow a sudden metabolic change (either an episode of diabetic ketoacidosis or occasionally an improvement in glycaemic control), when the duration of diabetes is relatively short, or when marked weight loss precedes the onset of pain.
Tricyclic antidepressant drugs – Many tricyclic antidepressant drugs (but not selective serotonin reuptake inhibitors) have been found in double-blind, placebo-controlled trials to improve symptoms in patients with painful diabetic neuropathy. The therapeutic effect usually occurs sooner (within six weeks) and at lower doses than is typical when these drugs are given for the treatment of depression eg 25mg
Amitriptyline. There is no correlation between relief of pain, dosage, or plasma drug concentrations, suggesting that the clinical response and tolerability of side effects are the best guides to dose titration.
Capsaicin cream – Capsaicin is a naturally occurring component of many hot peppers, and causes analgesia through local depletion of substance P. It is available in a cream for topical application and applied (0.075%) topically four times daily over painful areas. Local burning and skin irritation can occur but this becomes less of a problem with continued use.
Anticonvulsant drugs – If neuropathic pain continues, a third drug, most often Carbamazepine can be added. Phenytoin can be used as an alternative.
Gabapentin (300 to 600 mg three times per day) has also been used with moderate success. The major side effects were dizziness and confusion and it is considerably more expensive than Amitriptyline, but may be better tolerated at the doses required to treat neuropathy.
Other Treatments
Tramadol, NSAIDs and TENS have also been used with some success.
Diabetic Foot Ulcers
Classification – A useful simple classification of diabetic foot ulcers is:
- Grade 0 – No ulcer in a high-risk foot.
- Grade 1 – Superficial ulcer involving the full skin thickness but not underlying tissues.
- Grade 2 – Deep ulcer, penetrating down to ligaments and muscle, but no bone involvement or abscess formation.
- Grade 3 – Deep ulcer with cellulitis or abscess formation, often with osteomyelitis.
- Grade 4 – Localised gangrene.
- Grade 5 – Extensive gangrene involving the whole foot.
The intensity and duration of treatment can be determined by clinical evaluation of the ulcer. The usual approach to the management of lesions of each grade is given below, followed by a discussion of some newer approaches.
Grade 1 And 2 Lesions – There has been much discussion concerning which patients with these lesions need to be admitted to hospital for complete bed rest, the extent of the diagnostic evaluation, and the need for parenteral antibiotics to treat infection. Infection is likely to be present if the ulcer contains obvious purulent material or there is redness, swelling or warmth around the ulcer.
Studies indicate that extensive debridement, good local wound care, and relief of pressure on the ulcer are important components of therapy for foot ulcers. This treatment program does not require hospitalisation. Close monitoring is required, and hospitalisation for bed rest and intravenous antibiotic therapy is advisable if the ulcer does not improve.
Several devices can be used to relieve pressure on the ulcer, including removable cast walkers, half-shoes, and total contact casts.
Grade 3 Lesions – Before deciding upon appropriate management of deep ulcers, it is important to evaluate whether or not there is substantial peripheral vascular disease or bony involvement.
Evaluation for peripheral arterial disease – Symptoms of claudication, cool temperature, and the absence of hair should raise suspicion about the presence of peripheral arterial disease, but are neither sensitive nor specific enough to be helpful in an individual patient. More useful tests are examination of lower limb pulses and measurement of the ratio of blood pressure at the ankle to that in the brachial artery (the ankle-to-arm index) also correlates well with the presence of arterial occlusive disease. This index is calculated by measuring the systolic blood pressure (by Doppler probe) in the brachial, posterior tibial, and dorsalis pedis arteries. The highest of the four measurements in the ankles and feet is divided by the higher of the two brachial measurements. The normal index is >1.0, because the pressure is higher in the ankle than in the arm. An index <0.9 has 95 percent sensitivity for detecting angiogram-positive peripheral arterial disease. A low ankle-to-arm index also indicates more generalised arteriosclerosis, and is associated with an increased risk of cardiovascular death [8].
Evaluation for bone involvement – Osteomyelitis is likely to be present (positive predictive value of approximately 90%) if bone can be seen at the floor of a deep ulcer or if it can be easily detected by probing the ulcer with a sterile, blunt, stainless steel probe. Other signs that suggest osteomyelitis are an ulcer deeper than 3 mm and an otherwise unexplained ESR above 40mm/hour.
Radiological tests may be useful if the diagnosis remains uncertain. The diagnosis is clear if osteomyelitis is visible on plain radiographs. However, x-ray changes occur late in the course of osteomyelitis and negative radiographs do not exclude it. Other imaging techniques that have been used include radionuclide bone imaging, magnetic resonance imaging and imaging with indium-labelled leukocytes.
Treatment – A short period of hospitalisation, with surgical debridement, culture of material obtained from deep in the ulcer, and a prolonged course (10 to 12 weeks) of intravenous antibiotics is still standard therapy. Some patients can be treated successfully by hospitalisation for intravenous antibiotic therapy for 48 hours, followed by appropriate oral antibiotic therapy at home. Detailed decision and cost-effectiveness analyses have suggested that, in patients with no systemic toxicity, a 10-week course of culture-guided oral antibiotic therapy may be as effective and less costly than other approaches. Regardless of the approach chosen, it is essential that the patient is seen frequently and hospitalisation considered if the lesion is deteriorating. Surgical removal of infected bone may be necessary if the ulcer is not healing. An alternative to prolonged bed rest for the relief of pressure that allows ambulation is total contact casting which is often preferred by patients, and can be cost effective if performed by an experienced team.
Grade 4 And 5 Lesions – Patients with these more advanced lesions require urgent hospital admission and surgical consultation, and all-too-often amputation is needed.
Newer Approaches – Several novel approaches have been reported that may improve ulcer healing, such as the use of topical or systemic hyperbaric oxygen and granulocyte-colony stimulating factor (G-CSF).