What is Diabetic Neuropathy?
Diabetic neuropathy is the nerve dysfunction and damage that is a result of long-standing and often poorly controlled diabetes mellitus (sugar diabetes). It is the most common complication of diabetes mellitus and these neurological disturbances may affect more than half of all cases of long term diabetes.
Diabetic neuropathy is a broad therm that encompasses a variety of clinical neurological syndromes. It can be in the form of focal neuropathy, polyneuropathy, or autonomic neuropathy. Although neuropathy is a common complication of long standing and uncontrolled diabetes mellitus, it is often ignored until the late stages of the disease. At this point, symptoms like paresthesia, numbness or tingling, especially of the legs, affects daily functioning and leads to repeated injuries that predisposes to the formation of diabetic ulcers.
How does diabetes damage nerves?
The exact mechanism behind diabetic neuropathy in not fully understood but it is generally accepted to be due to many factors. There are many other types of neuropathy but in this case it is attributed to diabetes mellitus if the condition is present in a diabetic patient and no other causes of neuropathy is evident.
Acute Diabetic Neuropathy
Diabetes can produce acute and often self-limiting type of neuropathies that is likely to result from vascular effects of diabetes. This means that the nerve damage arises as a result of compromised blood flow through the blood vessels of nerves.
Chronic Diabetic Neuropathy
The more common, chronic type of neuropathies in diabetes often results from metabolic factors related to diabetes. The most prominent factor linked to the development of diabetic neuropathy is long standing hyperglycemia (high blood glucose levels).
With long standing hyperglycemia, excess glucose in nerve cells can lead to activation of the polyol pathway with the production of sorbitol and fructose. These sugars, sorbitol and fructose, can accumulate in the nerve cells and increase the intracellular water content due to osmosis thereby leading to nerve dysfunction.
The hyperglycemia can also lead to non-enzymatic glycation of proteins present in peripheral nerves. The polyol pathway and non-enzymatic glycation can also increase the free radical formation and raises the oxidative stress leading to damage of the peripheral nerves.
A variety of other factors are also found to be related to diabetic neuropathy. An autoimmune mechanism may also play a part as monocytes (a type of white blood cell) infiltrates the autonomic nerve bundles and antibodies against sympathetic ganglia may also contribute to diabetic neuropathy. In addition, reduced nerve growth factor seen in diabetic patients may limit the ability of the nerves to regenerate.
Types of Diabetic Neuropathy
Distal Symmetrical (Sensorimotor) Polyneuropathy
This is the most common type of diabetic neuropathy and is seen in both type 1 and 2 diabetes. It affects the distal parts of the limbs – forearm, hand and fingers of the upper limb or lower leg, foot, toes of the lower limb.
Although the sensorimotor nerves are affected, it is the sensory component that is more severely impaired. This means that the sensory fibers involving pain, touch, temperature and vibration are affected and these sensations are disrupted. This type of diabetic neuropathy does not set in immediately but gradually progresses over months and years.
In the early stages, a patient is asymptomatic but a thorough neurological examination can reveal some level of impairment. As the condition progresses the patient develops tingling and numbness of the distal extremities distributed in the “glove-stocking” pattern. Patients may also complain of pain which gradually increases in severity.
Severe sensory loss is only seen in the late stages. There is also wasting of the small muscles of the hands and feet and this may even cause difficulty in walking. There may also be joint involvement (Charcot joints / neuropathic joints).
Autonomic neuropathy can affect the autonomic nerve supply of any organ in body. It is more frequently seen in type 1 diabetes and commonly occurs in patients with distal symmetric polyneuropathy (above). Autonomic neuropathy symptoms can range from very mild to very severe. The prognosis for autonomic diabetic neuropathy is poor and severe forms can even cause sudden death.
Majority of patients with clinically significant symptoms have autonomic neuropathy that predominantly affects the cardiovascular, gastrointestinal or genitourinary systems. The symptoms depends on the organ involved.
Cardiovascular autonomic neuropathy can lead to increased heart rate at rest, defective heart rate responses to exertion, and painless myocardial ischemia. Such patients are at high risk for myocardial infarction (heart attack) and sudden cardiac death.
Impairment of sympathetic vasoconstrictor responses and defective cardiac reflexes leads to postural hypotension. This may be serious enough to warrant the use of medication.
The most common manifestation of gastrointestinal neuropathy is constipation. Another common complaint seen is diarrhea. Diabetic diarrhea can also be caused by increased motility of gut, intestinal irritation caused by bile, decreased motility with bacterial overgrowth, or pancreatic dysfunction. Patients can suffer from disabling gastroparesis which is manifested by nausea, vomiting, abdominal bloating and loss of appetite.
Autonomic neuropathy of the genitourinary system leads to dribbling, incomplete emptying of the bladder and urinary incontinence. Male diabetic patients are also susceptible to erectile dysfunction.
5. Sudomotor Dysfunction
Sudomotor dysfunction is characterized by abnormal sweat production which can affect the moisture of the skin and thermoregulation (temperature control). It can lead to xerosis (dry skin), skin cracking, heat intolerance, heat stroke and a risk of skin infections. Other sudomotor dysfunctions may include reduced sweating in the lower limbs with excessive sweating in the upper body or increased sweating in relation to eating (gustatory sweating).
Focal Diabetic Neuropathies (Mononeuropathy)
Focal diabetic neuropathies usually have an abrupt onset and are frequently associated with pain. It may affect the peripheral and cranial nerves. These types of neuropathies are usually self-limiting and patients may recover spontaneously within 6 to 8 weeks. Commonly affected nerves include the median, radial, oculomotor and lateral popliteal nerves.
Diabetic patients are also found to have entrapment neuropathies which are chronic and slow progressing. Common entrapment neuropathies can involve the median (carpal tunnel syndrome), ulnar, radial, lateral popliteal, peroneal, and plantar nerves.
Proximal Motor Neuropathy (Diabetic Amyotrophy)
Proximal motor neuropathy usually affects type 2 patients and is more frequently seen in elderly men. The disease classically results in pain and weakness in thighs, hips, and buttocks.
Diagnosis of Diabetic Neuropathy
A detailed history and neurological examination is essential to reach a differential diagnosis. Detailed sensory testing is an essential component for the diagnosis of diabetic neuropathy and will include two-point discrimination, thermal discrimination, vibration perception threshold, light touch sensation, examination of gait and motor functions and testing of the tendon reflexes.
Nerve conduction studies and electromyography (EMG) are of useful in confirming the diagnosis. Nerve biopsy is an option but rarely indicated. Tilt-table testing is useful in confirming the diagnosis of postural hypotension in autonomic neuropathy. Investigations to exclude other types of neuropathies (like HIV, syphilis, heavy metal poisoning) are conducted as required.
Treatment of Diabetic Neuropathy
The disease development and progression can be limited with good diabetic control. Treatment options are currently limited to symptomatic management while other specific treatments like drugs for nerve regeneration are still experimental.
Several therapies have been used for neuropathic pain including :
- anticonvulsants like carbamazepine and pregabalin
- tricyclic antidepressants like amitriptyline, desipramine, and nortriptyline
- serotonin-norepinephrine reuptake inhibitors like duloxetine
Duloxetine and pregabalin are relatively recent additions to the therapeutic armory against the neuropathic pain Analgesics like tramadol may also be used.
Topical applications include :
- capsaicin cream
- lidocaine gel
Focal neuropathy is primarily managed with pain control and physical therapy if muscle function is affected. Entrapment neuropathy is managed with anti-inflammatory drugs while severe cases may require surgical correction.
Postural hypotension in cardiovascular autonomic neuropathy can be managed with conservative measures like head-end elevation of bed at night, and supportive elastic stockings in mild cases. Drug therapy is considered in severe cases of postural hypotension.
Diabetic Gastrointestinal Conditions
Diabetic gastroparesis is managed with prokinetic drugs like metoclopramide or mosapride and frequent small meals. If diarrhea is the predominant problem, suitable treatment with antidiarrheals, broad-spectrum antibiotics (for bacterial over growth), pancreatic enzymes (for pancreatic insufficiency), or cholestyramine (for intestinal irritation with bile) is also considered.
Genitourinary symptoms are benefited with parasympathomimetic agents like bethanechol. Erectile dysfunction is managed with oral phosphodiesterase-5-inhibitors (like sildenafil, tadalafil, vardenafil). If phosphodiesterase-5-inhibitors are contraindicated, then intracavernosal injections of alprostadil or papaverine may be a consideration.