Diabetic neuropathy

• What is Diabetic Neuropathy
• Statistics on Diabetic Neuropathy
• Risk Factors for Diabetic Neuropathy
• Progression of Diabetic Neuropathy
• Symptoms of Diabetic Neuropathy
• Clinical Examination of Diabetic Neuropathy
• How is Diabetic Neuropathy Diagnosed?
• Prognosis of Diabetic Neuropathy
• How is Diabetic Neuropathy Treated?
• Diabetic Neuropathy References

What is Diabetic Neuropathy

Diabetic neuropathy is a type of nerve damage that happens in people who have diabetes mellitus. It affects mainly the peripheral nerves.
There are three types of peripheral nerve affected: motor, sensory, and autonomic. Motor nerve fibres carry signals to muscles to allow motions like walking and fine finger movements. Sensory nerves take messages in the opposite direction. They carry information to the brain about shape, movement, texture, warmth, coolness, or pain from special sensors in the skin and from deep in the body. Autonomic nerves are nerves that are not consciously controlled. These nerves have functions such as controlling the heart rate, maintaining blood pressure, and controlling sweating.
Damage to these nerves makes it hard for the nerves to carry messages to the brain and other parts of the body. This can result in numbness (loss of feeling) or painful tingling in parts of the body.
Diabetic neuropathy can also affect the following:

• Strength and feeling in different body parts.
• Ability of the heart to keep up with the body’s needs.
• Ability of the intestines to digest food.
• Ability to achieve an erection (in men).

Statistics on Diabetic Neuropathy

Diabetes mellitus is a common medical condition in the Australian community. It is estimated that approximately one in four Australians over the age of 25 years has diabetes or its precursor, impaired glucose metabolism (also associated with increased risk of heart disease). People with diabetes can develop nerve problems at any time, but the longer a person has diabetes, the greater the risk. Patients with type 2 diabetes are at greater risk particularly if they have poor control of their blood sugars. The highest rates of neuropathy are among people who have had the disease for at least 25 years.
An estimated 10 to 65% of those with diabetes have some form of neuropathy, but not all with neuropathy have symptoms. Painful diabetic neuropathy affects approximately one quarter of patients with diabetes. Diabetic neuropathy also appears to be more common in people who have had problems controlling their blood glucose levels, in those with high levels of cholesterol and high blood pressure, in overweight people, and in people over the age of 40.
The most common type is peripheral neuropathy, also called distal symmetric neuropathy, which affects the arms and legs. This is experienced by approximately 50% of diabetic patients suffering from neuropathy. Diabetic neuropathy also appears to be more common in males than in females.

Risk Factors for Diabetic Neuropathy

Diabetes can damage peripheral nervous tissue in a number of ways. There are many theories that have been suggested, and it is generally accepted that there are multiple causes of diabetic neuropathy. These causes are probably different for the different types of diabetic neuropathy.
Overall, the most significant risk factor for the development and progression of diabetic neuropathy is glycaemic control. Glycaemic control refers to how well a patient’s blood sugar level is kept within normal (physiological) limits.
Other risk factors for the development of diabetic neuropathy include:

• Increasing age;
• Genetic risk;
• Cigarette smoking;
• Alcohol use;
• High blood pressure;
• Hypercholesterolaemia (high blood cholesterol).

Note that many of these risk factors are potentially modifiable. Controlling the above risk factors will therefore prevent disease.

Progression of Diabetic Neuropathy

Peripheral neuropathy (distal symmetric polyneuropathy)
Peripheral neuropathy affects the nerves in the arms, hands, legs, and feet. The feet and legs are likely to be affected before the hands and arms. You may notice signs such as pain, weakness, reduced sensation or altered sensations (such as increased sensitivity to pain or touch). The classic description of diabetic neuropathy is called a ‘glove and stocking anaesthesia’. This refers to altered sensation that first develops in the extremities and slowly progresses to involve more proximal areas. Many people with diabetes have signs of neuropathy upon examination but have no symptoms at all.
Poor sensation in the feet can lead to complications such as severe ulcers, infections and in extreme circumstances the need for amputation. Peripheral neuropathy may also cause muscle weakness and loss of reflexes, especially at the ankle, leading to changes in gait (walking). Foot deformities, such as hammertoes and the collapse of the midfoot, may occur. Blisters and sores (ulcers) may appear on numb areas of the foot because pressure or injury goes unnoticed.
If foot injuries are not treated promptly, the infection may spread to the bone, and the foot may then have to be amputated. Some experts estimate that half of all such amputations are preventable if minor problems are caught and treated in time.
Autonomic neuropathy
Autonomic neuropathy affects the nerves in the lungs, heart, stomach, intestines, bladder, and sex organs.
Autonomic neuropathy affects the nerves that control the heart, regulate blood pressure, and control blood glucose levels. It also affects other internal organs, causing problems with digestion, respiratory function, urination, sexual response, and vision.
In addition, the system that restores blood glucose levels to normal after a hypoglycaemic (low blood sugar) episode may be affected, resulting in loss of the warning signs of hypoglycaemia such as sweating and palpitations.
This type of neuropathy is rare.
Proximal neuropathy
Proximal neuropathy, sometimes called lumbosacral plexus neuropathy, femoral neuropathy, or diabetic amyotrophy, starts with pain in either the thighs, hips, buttocks, or legs, usually on one side of the body.
This type of neuropathy is more common in those with type 2 diabetes and in older people. It causes weakness in the legs, manifested by an inability to go from a sitting to a standing position without help. Treatment for weakness or pain is usually needed. The length of the recovery period varies, depending on the type of nerve damage.
Focal neuropathy
Occasionally, diabetic neuropathy appears suddenly and affects specific nerves, most often in the head, torso, or leg. Focal neuropathy is painful and unpredictable and occurs most often in older people. However, it tends to improve by itself over weeks or months and does not cause long-term damage.
People with diabetes also tend to develop nerve compressions, also called entrapment syndromes. One of the most common is carpal tunnel syndrome, which causes numbness and tingling of the hand and sometimes muscle weakness or pain. Other nerves susceptible to entrapment may cause pain on the outside of the shin or the inside of the foot.

Symptoms of Diabetic Neuropathy

Symptoms of diabetic neuropathy depend on the type of neuropathy and which nerves are affected. Some people have no symptoms at all. For others, numbness, tingling, or pain in the feet is often the first sign. A person can experience both pain and numbness.
Often, symptoms are minor at first, and since most nerve damage occurs over several years, mild cases may go unnoticed for a long time. As the condition progresses and more nerve fibres are affected, you may experience sensory loss, numbness, loss of coordination and even motor (movement) problems.
The symptoms usually start in the peripheries and gradually progress more centrally. The involuntary (autonomic) nervous system may also be affected. In some people, mainly those with focal neuropathy, the onset of pain may be sudden and severe.
Symptoms may include:

• Numbness, tingling, or pain in the toes, feet, legs, hands, arms, and fingers;
• Wasting of the muscles of the feet or hands;
• Indigestion, nausea or vomiting;
• Diarrhoea or constipation;
• Dizziness or faintness due to a drop in blood pressure on standing;
• Problems with urination;
• Erectile dysfunction (impotence) or vaginal dryness;
• Weakness;
• Hypoglycaemia (low blood sugar) unawareness, a condition in which people no longer experience the warning signs of hypoglycaemia.

In addition, the following symptoms are not due to neuropathy but nevertheless often accompany it:

• Weight loss;
• Depression.

Clinical Examination of Diabetic Neuropathy

Any patient presenting with diabetes and sensory changes to the hands or feet should have a comprehensive foot exam to assess skin, circulation, and sensation. The test can be done during a routine office visit. To assess protective sensation or feeling in the foot, a nylon monofilament (similar to a bristle on a hairbrush) attached to a wand may be used to touch the foot. Those who cannot sense pressure from the monofilament have lost protective sensation and are at risk for developing foot sores that may not heal properly. Pinprick sensation may also be assessed.
Other tests include checking reflexes and assessing vibration perception, which is more sensitive than light touch perception.

How is Diabetic Neuropathy Diagnosed?

It is important to measure HbA1c (glycated haemoglobin) to assess blood sugar control.
More specific tests may be required depending on the symptoms. These may include:

• Nerve conduction studies check the transmission of electrical current through a nerve. With this test, an image of the nerve conducting an electrical signal is projected onto a screen. Nerve impulses that seem slower or weaker than usual indicate possible damage. This test allows the doctor to assess the condition of all the nerves in the arms and legs.
• Electromyography (EMG) shows how well muscles respond to electrical signals transmitted by nearby nerves. The electrical activity of the muscle is displayed on a screen. A response that is slower or weaker than usual suggests damage to the nerve or muscle. This test is often done at the same time as nerve conduction studies.
• Quantitative sensory testing (QST) uses the response to stimuli, such as pressure, vibration, and temperature, to check for neuropathy. QST is increasingly used to recognize sensation loss and excessive irritability of nerves.
• A check of heart rate variability shows how the heart responds to deep breathing and to changes in blood pressure and posture.
• An ultrasound uses sound waves to produce an image of internal organs. An ultrasound of the bladder and other parts of the urinary tract, for example, can show how these organs preserve a normal structure and whether the bladder empties completely after urination.

Prognosis of Diabetic Neuropathy

The prognosis for diabetic neuropathy depends largely on how well the underlying condition of diabetes is handled. Treating diabetes may halt progression and improve symptoms of the neuropathy, but recovery is slow.
Neuropathy can cause a significant burden on your life. Severe symptoms at night may contribute to sleep deprivation and depressive syndromes. Pain may also impede your overall quality of life, general activity, mobility, employment, social activities and necessitate greater use of health services.

How is Diabetic Neuropathy Treated?

Treatment of diabetic neuropathy is difficult and often requires a multidisciplinary (i.e. multiple factors) approach. Most treatment methods do not provide full relief of symptoms. At present, treatment alleviates pain and can control some associated symptoms, but reversal of the underlying process is rare.
General measures
Strict glycaemic (blood sugar) control with diet and medication is important to slow progression of disease. It is important not only to have good average control, but also to avoid large fluctuations in blood sugar levels. This may reduce severity of symptoms. In addition, your doctor may educate you regarding other risk factors for neuropathy. You should try to stop smoking and ensure any co-morbid conditions such as high blood pressure and high cholesterol are well under control. It is important you take your recommended medications for your diabetes and other conditions as prescribed.
If peripheral neuropathy is present, then good foot care with referral to a podiatrist can help to prevent development of complications such as ulcers.
Symptomatic management
A wide range of medications including analgesics, tricyclic antidepressants, local anaesthetics and some anticonvulsant medications may be prescribed for relief of neuropathic pain.
Anticonvulsant medications are now considered the best treatments to relieve symptoms of diabetic neuropathy. Overall they are the most effective agents with the lowest side effects. Typical treatments include gabapentin (Neurontin) and pregabalin (Lyrica). The latter is generally well tolerated and may cause less sedation than gabapentin.
More traditional anticonvulsants such as carbamazepine (Tegretol) and sodium valproate (Epilim) may also be effective. Of the tricyclic antidepressants, amitriptyline (Endep), imipramine and clomipramine have been shown to be most effective in the management of neuropathic pain. They are inexpensive but can be associated with several side effects, including dry mouth, blurred vision and urinary retention.
Analgesics such as opiates and tramadol have been used to treat neuropathic pain, with varying success.
Some patients find relief with topical therapies such as capsaicin cream. This may have side effects including local irritation (burning or rash), coughing or sneezing, and accidental irritation to other body parts.
Non-pharmacological methods of pain relief include walking regularly, taking warm baths, or using elastic stockings to help relieve leg pain.
Autonomic neuropathy
Symptoms of autonomic neuropathy should be managed individually. Some pharmacological agents are available, for example oral sildenafil for erectile dysfunction or metoclopramide for problems with digestion.
Disease modifying therapies
Numerous drugs have been trialled with the aim of reversing the underling disease process. Examples include aldose reductase inhibitors (such as ranirestat), alpha-lipoic acid, gamma-linoleic acid, and nerve growth factor. However, no agent has been found that can reliably halt progression of disease. Most treatments are therefore focussed on prevention or symptomatic mangement.
 
Article kindly reviewed by:
Associate Professor Karl Ng MB BS (Hons I) FRCP FRACP PhD CCT Clinical Neurophysiology (UK) Consultant Neurologist – Sydney North Neurology and Neurophysiology (download referral form and map); Conjoint Associate Professor – Sydney Medical School, University of Sydney; and Editorial Advisory Board Member of the Virtual Neuro Centre.
 

Diabetic Neuropathy References

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Drugs/Products Used in the Treatment of This Disease:

• Viagra (Sildenafil citrate)
• Carbamazepine-BC (Carbamazepine)
• Clomipramine (Terry White Chemists) (Clomipramine hydrochloride)
• DBL Gabapentin Capsules (Gabapentin)
• Endep (Amitriptyline hydrochloride)
• Epilim (Sodium valproate)
• Florinef (Fludrocortisone acetate)
• Lyrica (Pregabalin)
• Robinul Injectable (Glycopyrrolate)
• Tegretol (Carbamazepine)
• Tofranil (Imipramine hydrochloride)
• Zostrix HP (Capsaicin)