Diabetic Neuropathy -An Update

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Diabetic Neuropathy (Nerve Damage) - An Update

Nerve damage or Diabetic Neuropathy resulting from chronically high blood

sugars can be one of the most frustrating and debilitating complications

of diabetes because of the pain, discomfort and disability it can cause,

and because available treatments are not uniformly successful.

Some patients find some relief from this nerve damage or neuropathy by

keeping blood sugars as closely controlled as possible, getting regular

exercise and keeping their weight under control. Using non-narcotic pain

relievers consistently throughout the day - rather than waiting until

nighttime when symptoms can become more severe - also seems to help if

pain is the major symptom. Surprisingly, clinicians have found that

certain antidepressants may be helpful and can take the edge off the pain

of neuropathy as well.

While pain or numbness in the legs or feet may be the most common

complaint from people diagnosed with neuropathy, it is not the only

symptom of this complication. Neuropathy can cause a host of different

types of symptoms, depending on whether nerves in the legs, the

gastrointestinal tract, or elsewhere in the body are affected. If you

have any of these symptoms, neuropathy may be the culprit:

•inability to adequately empty the bladder of its contents, resulting in

frequent infections;

•nausea, vomiting, abdominal fullness or bloating, diarrhea, or

constipation;

•low blood pressure upon standing that causes fainting or dizziness;

•inability to lift the foot or new deformities of the foot, or foot

ulcers;

•trouble achieving or maintaining an erection.

While physicians have found some medications and other treatments that

help ease these symptoms in some people, prevention continues to be the

key. " Hemoglobin A1c readings should ideally be at 7.0 or below. Those

that are consistantly near or above 8 percent cause concern that any

diabetes complication, including neuropathy, may develop, " says

Hare, M.D., medical director of Joslin's Affiliated Center's program.

" The good news is that the Diabetes Control and Complications Trial shows

that people who keep their blood sugars consistently in this healthful

range can decrease their risk of nerve damage by over 50 percent. Getting

diabetes under better control also may help limit the amount of damage

caused by neuropathy once it's developed. "

If your doctor has told you that symptoms you have been experiencing are

a result of neuropathy, you certainly have many questions. Here are some

answers that may be helpful to you as you battle this complication.

What are the different types of neuropathy?

There are three broad types of neuropathy: sensory, autonomic and motor:

•Sensory neuropathy (or peripheral neuropathy, usually just called

neuropathy) affects the nerves that carry information to the brain about

sensations from various parts of the body - how hot or cold something is,

what the texture of something feels like, the pain caused by a sharp

object or heat, etc. This is the most common form of diabetic neuropathy.

•Autonomic neuropathy affects the nerves that control involuntary

activities of the body, such as the action of the stomach, intestine,

bladder and even the heart.

•Motor neuropathy affects the nerves that carry signals to muscles to

allow motions like walking and moving fingers. This form of neuropathy is

very rare in diabetes.

Sensory neuropathy can lead to pain, numbness or tingling in the

extremities and, ultimately, an inability to feel heat, cold, pain or any

other sensation in affected areas. Autonomic neuropathy can lead to

impotence in men, bladder neuropathy (which means the bladder is unable

to empty completely), diabetic diarrhea, or bloated stomach. Motor

neuropathy can lead to muscle weakness.

If you are diagnosed with neuropathy, your physician may use terms to

describe the type that you have based on whether only one side of your

body is affected (asymmetric) or both sides (symmetric). If only one kind

of nerve is affected, your doctor may say you have mononeuropathy. If

several nerves are affected, the term polyneuropathy may be used.

Other terms may be used based on what parts of the body are affected:

•Distal Neuropathy - is a form of sensory neuropathy that affects the

hands or feet. It can be asymmetric but is usually symmetric, and is the

most frequently diagnosed type of neuropathy

•Femoral neuropathy -- is painful sensory neuropathy that centers in the

thigh muscles. It can be asymmetric or symmetric.

•Diabetic amyotrophy - is motor neuropathy that affects the thigh nerves,

with resulting weakness often in addition to or instead of pain. It can

be symmetric or asymmetric.

•Gastroparesis -- is autonomic neuropathy that affects the stomach,

preventing it from emptying normally. It can result in ulcer-like

symptoms, vomiting, bloating, and poor absorption of food resulting in

malnutrition and hypoglycemic episodes as food fails to be absorbed at

the anticipated rate. High blood sugars can later result when the meal

finally makes its way through the system.

•Diabetic diarrhea - is autonomic neuropathy that results in an erratic

functioning of the small intestine. This can cause unformed stools to be

passed. If the nerves which communicate with the sphincter muscles (which

control passing a bowel movement) are not working properly, stool can

pass without warning, and/or without being able to control when it comes

out, resulting in fecal incontinence. Constipation also can result when

the large intestine is involved and the stool remains in the large

intestine too long.

•Bladder neuropathy - occurs when the bladder nerves no longer respond

normally to pressure as the bladder fills with urine, and do not enable

the bladder to empty completely. Some urine continually stays in the

bladder, leading to urinary tract infections. Symptoms of this problem

include cloudy urine, painful urination, low back pain and fever.

•Postural hypotension - is autonomic neuropathy that results in low blood

pressure when standing. In people with postural hypotension, the pulse

does not go up to compensate for the change in blood pressure, so

fainting and dizziness can result.

•Charcot joint- is also called neuropathic arthropathy and occurs when

the bones in the feet fracture or " powder " and the foot becomes

misaligned. The foot becomes deformed as a result of the lack of nerve

stimulation, which causes the muscles to lose the ability to support the

foot properly. Walking makes it worse. People who already have neuropathy

in their feet and have lost sensation are at a greater risk of developing

this.

*Unilateral foot drop - occurs when the foot can't be picked up because a

nerve in the leg has been damaged either by blood vessel disease or

compression.

*Impotence - is caused by autonomic neuropathy and/or sensory neuropathy,

and/or blood vessel disease that leads to an inability to have and

maintain an erection in men.

What is peripheral neuropathy and what causes it?

Peripheral neuropathy (more commonly called neuropathy) is a general term

for diseases that cause damage to the nerves outside of the brain and

spinal cord. While diabetes is a frequent cause of neuropathy, it is not

the only cause. Nutritional deficiencies (B-12 and folate), chemical

exposures, pressure on nerves, or medications (such as some of those used

for chemotherapy or to treat AIDS), can also cause neuropathy.

Theories abound as to why exactly neuropathy occurs in people with

diabetes. In general, diabetic neuropathy is thought to be a result of

chronic nerve damage caused by high blood sugars. " There are many

possible ways this might happen, " says Dr. Hare. " Nerves are surrounded

by a covering of cells, just like an electric wire is surrounded by

insulation. The cells surrounding a nerve are called Schwann cells. One

theory suggests that excess sugar circulating throughout the body

interacts with an enzyme in the Schwann cells, called aldose reductase.

Aldose reductase transforms the sugar into sorbitol, which in turn draws

water into the Schwann cells, causing them to swell. This in turn pinches

the nerves themselves, causing damage and in many cases pain. Unless the

process is stopped and reversed, both the Schwann cells and the nerves

they surround die. "

Another theory is that certain intracellular metabolites, such as

myoinositol, become depleted, leading to nerve damage. Still other

theories hold that pathways such as the protein kinase C pathway, being

studied by King, M.D., and his colleagues at Joslin, are triggered

by chronic high blood sugars, resulting in several diabetes

complications, perhaps including neuropathy.

" Recent studies have suggested that decreased blood flow to the nerves

can also contribute to the development of diabetic nerve disease, " says

Dr. King. There are multiple studies ongoing which are designed to

improve blood flow to the nerves in diabetic animals and in patients. Two

new categories of drugs being examined are called antioxidants and PKC

inhibitors. Preliminary studies using these drugs have shown encouraging

results in animal models of diabetes. Clinical trials are being planned

and some are already in progress.

How is neuropathy diagnosed?

People may seek their doctor's help for treatment of pain, not knowing

exactly what causes it. Men may come to the doctor concerned about a

decreasing ability to have and maintain an erection. Increasingly

frequent urinary tract infections may be another clue, as may be

recurring diarrhea or constipation, or vomiting or symptoms resembling an

ulcer. Fainting spells upon standing may indicate postural hypotension.

A physician may detect early signs of neuropathy. He or she may notice

that knee jerk and ankle jerk reflex tests show nerves aren't as

responsive as normal, or may observe a dip in blood pressure when you go

from a reclining to a sitting position. These are signs that increased

attention to blood sugars are warranted to try and limit further

problems.

A variety of tests, including electromyography (a test that measures the

response of muscles to electrical impulses) and nerve conduction studies

(a study of the flow of electrical current through the nerves) combined

with clinical observations may help a physician rule out other possible

causes of pain, and diagnose neuropathy. To diagnose Charcot foot

fracture, the doctor may take an x-ray and possibly do a bone scan.

How is it treated?

Unfortunately, there are no miracle cures or treatments for neuropathy,

although a variety of treatments are often helpful. There is no way to

heal or replace nerves that have been damaged.

The most important thing someone who has neuropathy can do is keep their

blood sugar levels as close to normal as possible, exercise regularly,

and make sure their weight is as close to what it should be as possible.

This will help keep blood sugars closer to normal and limit the damage

high blood sugars can cause to nerves. Exercise will have the added

benefit of keeping muscles that may be weakened by decreasing nerve

activity to remain strong and toned. Dr. Hare says he finds that patients

with painful neuropathy say the pain seems less severe if they get some

simple exercise regularly.

Patients with painful neuropathy will try almost any kind of pain

reliever their physicians will give them. " One can try a variety of

non-narcotic pain killers, " says Dr. Hare. " But one should stay away from

the more powerful narcotics, which do not work very well for neuropathy,

but will lead to addiction. "

Dr. Hare recommends acetaminophen (Tylenol®), aspirin and ibuprofen

(Motrin ® Advil ®:, etc.) first. Pain medicines are best used regularly

throughout the day, rather than waiting for pain to become severe. At

that point, pain medicines are less able to stem the tide, says Dr. Hare.

Some physicians recommend creams that contain capsaicin, an extract of

the hot capsicum pepper (which includes red, cayenne and tabasco peppers)

and can be rubbed on the skin over the pain. It is believed in some

circumstances that these creams block pain signals, although they do not

work for everyone - occasionally, they may even worsen the pain in some

patients or cause other adverse effects, like eye or skin irritation. Be

sure to check with your doctor before trying such products and follow

application instructions carefully. Capsaicin, which has been approved by

the Food and Drug Administration for treating pain, is available in over

the counter topical salves that include ArthiCare®: and Zostrix®:.

Certain antidepressants also seem to be particularly helpful for pain,

says Dr. Hare. Elavil ®: (amitriptyline), Norpramin®: (desipramine) or

Imipramine®: are members of the tricyclic antidepressant category of

drugs. These medications are not prescribed because the patient is

depressed - " although having constant pain for months can be depressing, "

notes Dr. Hare. " Rather, it seems that the medications block the pain.

Patients take them at night, and they have the effect of helping patients

tune the pain out. When I prescribe them to patients, I explain that it's

kind of like having a full bladder. If you aren't doing anything, you

notice the full bladder and you feel the need to go to the bathroom right

away. But if you're engrossed in a TV show, you don't notice it as much

and can go for quite a while before going to the bathroom. These

anti-depressants have largely the same effect on pain, helping patients

notice it less. Because the pain is usually worse at night, patients take

the medication at night and it seems to help them sleep. It also helps

them with the depression and insomnia they may be experiencing as a

result of the neuropathy. "

" Antidepressants can take several weeks to become effective, so I tell

patients to give it a month before deciding whether it is helpful or

not, " says Dr. Hare. " These drugs can also cause dry mouth, which most

patients find not to be much of a problem. "

Other types of drugs that sometimes help are anti-convulsants such as

phenytoin (Dilantin®, carbamazepine (Tegretol® or gabapentin

(Neurontin®. Drugs such as mexiletine (Mexitil® normally used to

treat irregular heart rhythm, sometimes relieve neuropathy pain. Drugs

like metaxalone (Skelaxin® that generally depress the central nervous

system can help reduce muscle pain. All of these drugs, however, can have

such unpleasant side effects as dizziness or confusion when taken in

large doses, especially by elderly patients.

Many patients will ask their physician about the value of nutritional

supplements or vitamins to ease pain. " If the neuropathy is caused by a

vitamin deficiency, such as a B vitamin deficiency, taking B6 or B12 will

help, " notes Dr. Hare. " But if you're body is not deficient in these B

vitamins, the vitamins will just go down the drain in your urine. You'll

notice that your urine is a very bright yellow - but the treatment

probably won't do you any harm. As for other nutritional supplements or

vitamin treatments, there isn't anything that is widely accepted as being

useful-unfortunately. But other vitamins that are not so easily passed

through the urine can lead to vitamin toxicity. So you need to be careful

that you aren't taking too much of any vitamin supplement in the distant

hope of easing the pain. "

Some patients have experienced success will other forms of pain

management - biofeedback, meditation, acupuncture, etc. " I don't

discourage a person from trying any safe, non-drug approach to pain

relief, " says Dr. Hare. " What may not work for one person may work really

well for someone else. "

For gastroparesis, in which the stomach is not emptying properly,

physicians at Joslin may prescribe Reglan ®: (metoclopramide), which will

help the stomach push food and get it through the rest of the digestive

process. These may be used in conjunction with Carafate ®: (sucralfate)

which " helps to sop up extra acid that may be sitting in the stomach, "

Dr. Hare says.

For those experiencing bladder neuropathy, which results in the bladder

never completely emptying, Urecholine ®: may be prescribed. " This is a

urine propellant that helps to keep the bladder clear, " says Dr. Hare.

" Because patients with this problem will be more likely to develop

frequent urinary tract infections, the physician may also prescribe

chronic antibiotic therapy to try and keep the bacterial count in the

bladder and urinary tract at a manageable level. "

Impotence in men that is a result neuropathy or blood vessel damage

(versus psychological causes or due to medications such as

anti-depressants or blood pressure medication) can be treated using

certain drugs that are either inserted into the end of the penis or

injected to cause an erection before intercourse. Vacuum devices that

enable an erection to be achieved, or a surgically implanted prosthesis

are also options to be explored with a physician.

The drug Viagra is also an option, although patients should be sure to

check closely with their physician before taking the drug. People with

diabetes are more prone to heart and blood vessel disease than

non-diabetics, and the use of Viagra leading to the resumption of sexual

activity in individuals with underlying cardiovascular disease (diagnosed

or undiagnosed) should be reviewed with a physician. Also, the use of

Viagra with nitroglycerine tablets (a treatment for acute heart problems

such as angina or heart attack) has led to several reported deaths.

Finally, there is an unproven suspicion that usage may affect retinal

circulation (in addition to its known side effects).

Patients with postural hypotension may be prescribed certain blood

pressure raising medications or may benefit from support stockings to

prevent pooling of blood in the legs. For patients with diabetes who also

have high blood pressure, the process of balancing blood pressure

lowering medications with medications that will keep blood pressure from

dipping too low while reclining and then sitting up can be particularly

tricky, and may require several adjustments to fine-tune.

Charcot damage is addressed by avoiding putting any weight on the foot

while it heals. The foot is usually put into a cast for a period of weeks

to limit damage. Later, the patient wears special shoes. Surgery may be

needed to restore a more normal shape to the foot.

Some patients may remember a lot of talk in the late 1980s and early

1990s about a new class of drugs called aldose reductase inhibitors,

which it was thought might be a significant breakthrough in treating some

types of neuropathy. " Unfortunately, to date none of these drugs has

proven to be sufficiently effective and side-effects have been a concern.

As a result none have come to market to treat neuropathy yet, although

companies are still working to develop them, " says Dr. Hare.

How can further problems be avoided?

One of the major issues with neuropathy, particularly sensory neuropathy,

is that eventually the affected nerves die, and the patient experiences a

complete loss of sensation in the area. For this reason, if you have

developed neuropathy in your feet and legs, you need to check your feet

every day for cuts and other problems that you may no longer feel. You

need to make sure your shoes are in excellent condition and don't have

pebbles or rough spots in them that could damage feet without your

knowing about it. If you have neuropathy, you should not use heating pads

or electric blankets - you could be seriously burned without knowing it.

You should be especially careful when taking baths to ensure that the

water is not too hot, as it would be relatively easy to scald your feet

or legs if they have become desensitized to pain.

When will the pain end?

" There's no easy answer to the question, 'when will the pain end?', "

notes Dr. Hare. " Maybe if a patient gets their blood sugars under good

control, that will be enough to ease the pain. If it doesn't, perhaps a

daily regimen of Tylenol every few hours plus an anti-depressant at night

and regular exercise every day will make the pain manageable. It can take

up to two years for the pain of neuropathy - which is caused by ongoing

damage to the nerve - to be replaced by the numbness that occurs when the

nerve cells are more severely damaged. Our goal in the meantime is to

identify ways to help patients manage the pain and discomfort of

neuropathy, and to help patients lead as normal a life as possible

despite the pain or other side-effects caused by this complication. "

Marilyn

Moderator for

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Opinions expressed are solely

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