development of this neuropathy and are probably
closely related to diabetic control. There are
complex relationships between high blood sugar
levels, the enzyme aldosereductase, the formation of
You wake up in the middle of the night with
sorbitol in the cells, and myoinositol in the tissues,
burning and tingling in your feet. The weight of the
which have been implicated in the development of
sheets makes things worse, so you can forget about
neuropathy. Poor blood sugar control may also lead
falling asleep again. When you visit your doctor and
to glycosylation (attachment of glucose molecules
describe your symptoms, he tells you the t problem
to proteins) of the myelin coating nerve fibers, and
is your nerves. Does he mean that you're under too
this may contribute to the development of
much stress or that the problem is all in your mind?
Absolutely not. You are suffering from a very real
Not all cases of peripheral neuropathy in
condition known as neuropathy, which is damage to
people with diabetes are caused by the diabetes
the nerves caused by diabetes. Symptoms of
itself. Other disorders may cause it and your
diabetic neuropathy are more likely to occur if
physician should look for them. These include
diabetes has been present for many years, and
nutritional disorders (especially vitamin B
prevalence increases with increasing duration of
deficiencies), alcoholism, collagen vascular diseases
diabetes. Symptoms are often related to both short-
(such as lupus), some infectious diseases (such as
term and long-term blood sugar control. Sixty
leprosy), kidney failure, and disorders of the
percent of people with poor diabetic control have
pituitary and thyroid glands. There are also many
symptoms of neuropathy after 20 years, whereas
drugs that can cause peripheral neuropathy,
only 15% of people with good control for 20 years
including allopurinol (used for gout), vinblastine
and vincristine (anti-cancer drugs), hydralazine
(used for high blood pressure) , isoniazid (for
Mononeuritis simplex involves a single nerve with
tuberculosis), nitrofurantoin (often used for bladder
severe pain, and mononeuritis multiplex involves
and kidney infections), some sulfanilamides (a class
several nerves. Cranial nerve neuropathies may
of antibiotics), and others. If you have symptoms of
cause facial or eye abnormalities. Autonomic
neuropathy and are taking any of these medications,
neuropathies disrupt the working of internal organs,
your physician may be able to prescribe alternative
causing diarrhea, impotence, stomach bloating,
constipation, bladder dysfunction and similar
Research published last year using healthy,
nondiabetic individuals showed that they could not
Peripheral neuropathy, discussed here, may
tolerate as much pain when they were given an
affect only one nerve but more often affects many.
injection of glucose before a pain-perception and
It usually starts at the toes, feet, and then legs and
pain-tolerance test. In another study, 13 men with
spreads to the fingers, hands, and arms in a "glove
Type II (non-insulin-dependent) diabetes were
and stocking" distribution. Peripheral neuropathy
tested for their perception of pain. It was found that
may affect only the sensory nerves (which give us
compared with nondiabetic individuals, they could
the sense of touch) but may also affect motor
not sense nonpainful electrical stimulation until it
nerves, which control movement and strength. Pain
was at a much higher level--yet they perceived pain
may be severe or absent, and such sensations as
at a much lower level than nondiabetics. These
taste may also be affected. This decreased sense of
findings again suggest that good blood sugar control
taste may cause a person to add salt and sugar to his
may de- crease the symptoms of peripheral
diet in an attempt to regain flavor which, of course,
can be harmful to blood pressure and blood sugar
SYMPTOMS
Peripheral neuropathy may occur suddenly
but more often occurs gradually. Symptoms vary from individual to individual. The more common
symptoms are sensations described as dull, aching,
weeks. Carbamazepine (Tegretol) is often
tingling, numbness, itching, crawling, formication
successful in two weeks. Phenazopyridine
(like worms crawling in the legs), supersensitivity,
(Pyridium) and aspirin together have also worked
burning, stabbing, "dead," "woody," "asleep," or
for some patients. If you take one of these
"walking on air or cotton. " These symptoms are
medications and it fails to work, let your physician
typically worse at night in people with diabetes, and
know--an alternative drug may turn out to be more
often cause them to become depressed because of
constant discomfort and sleepless nights. Loss of
sensation may make a person incapable of telling
have read about is sorbinil, which might prove to
where his feet are if he can't see them, which may
help the discomfort and may be available for
cause him to fall when walking in the dark or on
general use within the next few years. One of the
stairs. Generally, a numb foot may result in more
problems with sorbinil is a high incidence of
serious consequences than a painful one, since the
intolerable side effects. Sorbinil may prove to be
numbness may prevent him from feeling foot
more useful in preventing neuropathy than treating
injuries and taking prompt action to prevent
infection or gangrene. (See "Side-stepping Foot
Problems" in the Spring 1985 issue of Diabetes
neuropathic pain is to interrupt the "gate" that
allows pain impulses to pass from the spinal cord
into the brain. This treatment, transcutaneous
neuropathy is getting better because the pain gives
electronic nerve stimulation (TENS) uses a small
way to numbness. This is not an improvement--it is
device with electrodes that send impulses from the
a worsening of the condition. The loss of pain is a
skin into the spinal cord to block these pain signals.
good sign only if normal sensation returns.
Other attempts at blocking pain messages include
hypnosis, acupuncture, relaxation techniques,
TREATMENT
rhythmic breathing, biofeedback, self-distraction,
Four out of five people with neuropathy will
have some improvement in their symptoms in 6-18
professionals, these techniques are successful in
months. Nonetheless, that seems a long time to wait
some patients. Other methods some patients have
if you are feeling discomfort. The best course would
tried successfully for temporary relief include
be to try to avoid it in the first place by getting your
dipping the affected part of the body in warm (not
blood sugar into control and keeping it there.
hot) or cool water, wearing a body stocking or panty
Therapy for peripheral neuropathy should
hose to decrease sensation from other objects, using
include good nutrition to avoid vitamin deficiencies,
a foot cradle over the bed to keep sheets from
avoiding alcohol and, perhaps, selecting foods that
touching the feet at night, and rubbing the affected
are rich in myoinositol--one of the chemicals that
area with analgesic balm such as Ben Gay. It is very
may be important for preventing the development of
neuropathy. These foods include nuts, whole grains,
appropriate padding, closed toes, and well-fitting
cherries, and melons. Do not take myoinositol
socks, and observe good nail hygiene. Exercises
tablets, since this may cause an overdose, making
may help to strengthen some of the muscles that
have been weakened by neuropathy. Avoid heating
There are several drugs your physician may
pads on areas that are numb, because you may get
prescribe for diabetic peripheral neuropathy. One is
burned without realizing it. Likewise, you should
Benadryl, a drug which can be taken at bedtime to
not test the water in your bathtub or shower with
help alleviate the discomfort and ensure a good
your foot or hand if their sensation of temperature is
night's sleep. The antidepressant class of drugs,
impaired. Rather, you should dip in the upper arm
such as amitriptyline (Elavil), trazadone (Desyrel),
to test the temperature before climbing in. Although
and fluphenazine (Prolixin), may be useful in
peripheral neuropathy is currently the most common
treating neuropathy as well as depression.
complication of diabetes, most people can find
Anticonvulsants such as phenytoin (Dilantin) are
relief from the symptoms-through good blood sugar
often helpful, especially for stabbing pain and, if
control and the many modes of therapy available.
effective, usually gives good results within two
The role and source of 5P-deoxyadenosyl radical in a carbon skeletonrearrangement catalyzed by a plant enzymeSandrine Ollagnier, Eric Kervio, Jaènos Reètey*Lehrstuhl fuër Biochemie, Institut fuër Organische Chemie, Universitaët Karlsruhe, Kaiserstr. 12, D-76128 Karlsruhe, GermanyReceived 15 August 1998; received in revised form 24 September 1998Abstract The last step in the biosynthesi