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What Is Diabetic Neuropathy?
Diabetic neuropathy is a nerve disorder caused by diabetes. Symptoms of neuropathy include numbness and sometimes pain in the hands, feet, or legs. Nerve damage caused by diabetes can also lead to problems with internal organs such as the digestive tract, heart, and sexual organs causing indigestion, diarrhea or constipation, dizziness, bladder infections, and impotence. In some cases, neuropathy can flare up suddenly, causing weakness and weight loss. Depression may follow. While some treatments are available, a great deal of research is still needed to understand how diabetes affects the nerves and to find more effective treatments for this complication.

Can Diabetic Neuropathy Be Prevented?
A 10-year clinical study that involved 1,441 volunteers with insulin-dependent diabetes (IDDM) was recently completed by the National Institute of Diabetes and Digestive and Kidney Diseases. The study proved that keeping blood sugar levels as close to the normal range as possible slows the onset and progression of nerve disease caused by diabetes. The Diabetes Control and Complications Trial (DCCT) studied two groups of volunteers: those who followed a standard diabetes management routine and those who intensively managed their diabetes. Persons in the intensive management group took multiple injections of insulin daily or used an insulin pump and monitored their blood glucose at least four times a day to try to lower their blood glucose levels to the normal range. After 5 years, tests of neurological function showed that the risk of nerve damage was reduced by 60% in the intensively managed group. People in the standard treatment group, whose average blood glucose levels were higher, had higher rates of neuropathy. Although the DCCT included only patients with IDDM, researchers believe that people with noninsulin-dependent diabetes would also benefit from maintaining lower levels of blood glucose.

How Common Is Diabetic Neuropathy?
People with diabetes can develop nerve problems at any time. Significant clinical neuropathy can develop within the first 10 years after diagnosis of diabetes and the risk of developing neuropathy increases the longer a person has diabetes. Some recent studies have reported that:

•30 to 40% of patients with diabetes have symptoms suggesting neuropathy, compared with 10% of people without diabetes.
Diabetic neuropathy appears to be more common in smokers, people over 40 years of age, and those who have had problems controlling their blood glucose levels.

What Causes Diabetic Neuropathy?
Scientists do not know what causes diabetic neuropathy, but several factors are likely to contribute to the disorder. High blood glucose, a condition associated with diabetes, causes chemical changes in nerves. These changes impair the nerves' ability to transmit signals. High blood glucose also damages blood vessels that carry oxygen and nutrients to the nerves. In addition, inherited factors probably unrelated to diabetes may make some people more susceptible to nerve disease than others.

How high blood glucose leads to nerve damage is a subject of intense research. The precise mechanism is not known. Researchers have discovered that high glucose levels affect many metabolic pathways in the nerves, leading to an accumulation of a sugar called sorbitol and depletion of a substance called myoinositol. However, studies in humans have not shown convincingly that these changes are the mechanism that causes nerve damage.

More recently, researchers have focused on the effects of excessive glucose metabolism on the amount of nitric oxide in nerves. Nitric oxide dilates blood vessels. In a person with diabetes, low levels of nitric oxide may lead to constriction of blood vessels supplying the nerve, contributing to nerve damage. Another promising area of research centers on the effect of high glucose attaching to proteins, altering the structure and function of the proteins and affecting vascular function.

Scientists are studying how these changes occur, how they are connected, how they cause nerve damage, and how to prevent and treat damage.

What Are the Symptoms of Diabetic Neuropathy?
The symptoms of diabetic neuropathy vary. Numbness and tingling in feet are often the first sign. Some people notice no symptoms, while others are severely disabled. Neuropathy may cause both pain and insensitivity to pain in the same person. Often, symptoms are slight at first, and since most nerve damage occurs over a period of years, mild cases may go unnoticed for a long time. In some people, mainly those afflicted by focal neuropathy, the onset of pain may be sudden and severe.

What Are the Major Types of Neuropathy?
The symptoms of neuropathy also depend on which nerves and what part of the body is affected. Neuropathy may be diffuse, affecting many parts of the body, or focal, affecting a single, specific nerve and part of the body.

Diffuse Neuropathy
The two categories of diffuse neuropathy are peripheral neuropathy affecting the feet and hands and autonomic neuropathy affecting the internal organs.

Peripheral Neuropathy. The most common type of peripheral neuropathy damages the nerves of the limbs, especially the feet. Nerves on both sides of the body are affected. Common symptoms of this kind of neuropathy are:

These symptoms are often worse at night.

The damage to nerves often results in loss of reflexes and muscle weakness. The foot often becomes wider and shorter, the gait changes, and foot ulcers appear as pressure is put on parts of the foot that are less protected. Because of the loss of sensation, injuries may go unnoticed and often become infected. If ulcers or foot injuries are not treated in time, the infection may involve the bone and require amputation. However, problems caused by minor injuries can usually be controlled if they are caught in time. Avoiding foot injury by wearing well-fitted shoes and examining the feet daily can help prevent amputations.
Autonomic Neuropathy (also called visceral neuropathy) Autonomic neuropathy is another form of diffuse neuropathy. It affects the nerves that serve the heart and internal organs and produces changes in many processes and systems.

Urination and Sexual Response Autonomic neuropathy most often affects the organs that control urination and sexual function. Nerve damage can prevent the bladder from emptying completely, so bacteria grow more easily in the urinary tract (bladder and kidneys). When the nerves of the bladder are damaged, a person may have difficulty knowing when the bladder is full or controlling it, resulting in urinary incontinence.

The nerve damage and circulatory problems of diabetes can also lead to a gradual loss of sexual response in both men and women, although sex drive is unchanged. A man may be unable to have erections or may reach sexual climax without ejaculating normally.

Digestion. Autonomic neuropathy can affect digestion. Nerve damage can cause the stomach to empty too slowly, a disorder called gastric stasis. When the condition is severe (gastroparesis), a person can have persistent nausea and vomiting, bloating, and loss of appetite. Blood glucose levels tend to fluctuate greatly with this condition.

If nerves in the esophagus are involved, swallowing may be difficult. Nerve damage to the bowels can cause constipation or frequent diarrhea, especially at night. Problems with the digestive system often lead to weight loss.

Cardiovascular System. Autonomic neuropathy can affect the cardiovascular system, which controls the circulation of blood throughout the body. Damage to this system interferes with the nerve impulses from various parts of the body that signal the need for blood and regulate blood pressure and heart rate. As a result, blood pressure may drop sharply after sitting or standing, causing a person to feel dizzy or light-headed, or even to faint (orthostatic hypotension).

Neuropathy that affects the cardiovascular system may also affect the perception of pain from heart disease. People may not experience angina as a warning sign of heart disease or may suffer painless heart attacks. It may also raise the risk of a heart attack during general anesthesia.

Hypoglycemia. Autonomic neuropathy can hinder the body's normal response to low blood sugar or hypoglycemia, which makes it difficult to recognize and treat an insulin reaction.

Sweating. Autonomic neuropathy can affect the nerves that control sweating. Sometimes, nerve damage interferes with the activity of the sweat glands, making it difficult for the body to regulate its temperature. Other times, the result can be profuse sweating at night or while eating (gustatory sweating).

Focal Neuropathy (Including Multiplex Neuropathy)
Occasionally, diabetic neuropathy appears suddenly and affects specific nerves, most often in the torso, leg, or head. Focal neuropathy may cause:

How Do Doctors Diagnose Diabetic Neuropathy?
A doctor diagnoses neuropathy based on symptoms and a physical exam. During the exam, the doctor may check muscle strength, reflexes, and sensitivity to position, vibration, temperature, and light touch. Sometimes special tests are also used to help determine the cause of symptoms and to suggest treatment.

A simple screening test to check point sensation in the feet can be done in the doctor's office. The test uses a nylon filament mounted on a small wand. The filament delivers a standardized 10-gram force when touched to areas of the foot. Patients who cannot sense pressure from the filament have lost protective sensation and are at risk for developing neuropathic foot ulcers.

Nerve conduction studies check the flow of electrical current through a nerve. With this test, an image of the nerve impulse is projected on a screen as it transmits an electrical signal. Impulses that seem slower or weaker than usual indicate possible damage to the nerve. This test allows the doctor to assess the condition of all the nerves in the arms and legs.

Electromyography (EMG) is used to see how well muscles respond to electrical impulses 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.

Ultrasound employs sound waves. The sound waves are too high to hear, but they produce an image showing how well the bladder and other parts of the urinary tract are functioning.

Nerve biopsy involves removing a sample of nerve tissue for examination. This test is most often used in research settings.

If your doctor suspects autonomic neuropathy, you may also be referred to a physician who specializes in digestive disorders (gastroenterologist) for additional tests.

How Is Diabetic Neuropathy Usually Treated?
Treatment aims to relieve discomfort and prevent further tissue damage. The first step is to bring blood sugar under control by diet and oral drugs or insulin injections, if needed, and by careful monitoring of blood sugar levels. Although symptoms can sometimes worsen at first as blood sugar is brought under control, maintaining lower blood sugar levels helps reverse the pain or loss of sensation that neuropathy can cause. Good control of blood sugar may also help prevent or delay the onset of further problems.

Another important part of treatment involves special care of the feet, which are prone to problems.

A number of medications and other approaches are used to relieve the symptoms of diabetic neuropathy.

Relief of Pain
For, burning, tingling, or numbness, the doctor may suggest an analgesic such as aspirin or acetaminophen or anti-inflammatory drugs containing ibuprofen. Nonsteroidal anti-inflammatory drugs should be used with caution in people with renal disease. Antidepressant medications such as amitriptyline (sometimes used with fluphenazine) or nerve medications such as carbamazepine or phenytoin sodium may be helpful. Codeine is sometimes prescribed for short-term use to relieve severe pain. In addition, a topical cream, capsaicin, is now available to help relieve the pain of neuropathy.
The doctor may also prescribe a therapy known as transcutaneous electronic nerve stimulations (TENS). In this treatment, small amounts of electricity block pain signals as they pass through a patient's skin. Other treatments include hypnosis, relaxation training, biofeedback, and acupuncture. Some people find that walking regularly or using elastic stockings helps relieve leg pain. Warm (not hot) baths, massage, or an analgesic ointment such as Ben Gay may also help.

Gastrointestinal Problems
Indigestion, belching, nausea, or vomiting are symptoms of gastroparesis. For patients with mild symptoms of slow stomach emptying, doctors suggest eating small, frequent meals and avoiding fats. Eating less fiber may also relieve symptoms. For patients with severe gastroparesis, the doctor may prescribe metoclopramide, which speeds digestion and helps relieve nausea. Other drugs that help regulate digestion or reduce stomach acid secretion may also be used or erythromycin may be prescribed. In each case, the potential benefits of these drugs need to be weighed against their side effects.

To relieve diarrhea or other bowel problems, antibiotics or clonidine HCl, a drug used to treat high blood pressure, are sometimes prescribed. The antibiotic tetracycline may be prescribed. A wheat-free diet may also bring relief since the gluten in flour sometimes causes diarrhea.

Neurological problems affecting the urinary tract can result in infections or incontinence. The doctor may prescribe an antibiotic to clear up an infection and suggest drinking more fluids to prevent further infections. If incontinence is a problem, patients may be advised to urinate at regular times (every 3 hours, for example) since they may not be able to tell when the bladder is full.

Dizziness, Weakness
Sitting or standing slowly may help prevent light-headedness, dizziness, or fainting, which are symptoms that may be associated with some forms of autonomic neuropathy. Raising the head of the bed and wearing elastic stockings may also help. Increased salt in the diet and treatment with salt-retaining hormones such as fludrocortisone are other possible approaches. In certain patients, drugs used to treat hypertension can instead raise blood pressure, although predicting which patients will have this paradoxical reaction is difficult.

Muscle weakness or loss of coordination caused by diabetic neuropathy can often be helped by physical therapy.

Urinary and Sexual Problems
Nerve and circulatory problems of diabetes can disrupt normal male sexual function, resulting in impotence. After ruling out a hormonal cause of impotence, the doctor can provide information about methods available to treat impotence caused by neuropathy. Short-term solutions involve using a mechanical vacuum device or injecting a drug called a vasodilator into the penis before sex. Both methods raise blood flow to the penis, making it easier to have and maintain an erection. Surgical procedures, in which an inflatable or semirigid device is implanted in the penis, offer a more permanent solution. For some people, counseling may help relieve the stress caused by neuropathy and thereby help restore sexual function.

In women who feel their sexual life is not satisfactory, the role of diabetic neuropathy is less clear. Illness, vaginal or urinary tract infections, and anxiety about pregnancy complicated by diabetes can interfere with a woman's ability to enjoy intimacy. Infections can be reduced by good blood glucose control. Counseling may also help a woman identify and cope with sexual concerns.

Why Is Good Foot Care Important for People with Diabetic Neuropathy?
People with diabetes need to take special care of their feet. Neuropathy and blood vessel disease both increase the risk of foot ulcers. The nerves to the feet are the longest in the body, and are most often affected by neuropathy. Because of the loss of sensation caused by neuropathy, sores or injuries to the feet may not be noticed and may become ulcerated.

At least 15% of all people with diabetes eventually have a foot ulcer, and 6 of every 1,000 people with diabetes have an amputation. However, doctors estimate that nearly three quarters of all amputations caused by neuropathy and poor circulation could be prevented with careful foot care.

To prevent foot problems from developing, people with diabetes should follow these rules for foot care:

Are There Any Experimental Treatments for Diabetic Neuropathy?
Several new drugs under study may eventually prevent or reverse diabetic neuropathy. However, extensive testing is required by the U.S. Food and Drug Administration to establish the safety and efficacy of drugs before they are approved for widespread use.

Researchers are exploring treatment with a compound called myoinositol. Early findings have shown that nerves in diabetic animals and humans have less than normal amounts of this substance. Myoinositol supplements increase the levels of this substance in tissues of diabetic animals, but research is still needed to show any concrete lasting benefits from this treatment.

Another area of research concerns the drug aminoguanidine. In animals, this drug blocks cross-linking of proteins that occurs more quickly than normal in tissues exposed to high levels of glucose. Early clinical tests are under way to determine the effects of aminoguanidine in humans.

One approach that appeared promising involved the use of aldose reductase inhibitors (ARIs). ARIs are a class of drugs that block the formation of the sugar alcohol sorbitol, which is thought to damage nerves. Scientists hoped these drugs would prevent and might even repair nerve damage. But so far, clinical trials have shown that these drugs have major side effects and, consequently, they are not available for clinical use.

Some General Hints
•Ask your doctor to suggest an exercise routine that is right for you. Many people who exercise regularly find the pain of neuropathy less severe. Aside from helping you reach and maintain a healthy weight, exercise also improves the body's use of insulin, helps improve circulation, and strengthens muscles. Check with your doctor before starting exercise that can be hard on your feet, such as running or aerobics.