18.2 million people living in the United States are diabetics.
This number represents over 6.3% of the population. One of the most common
complications of diabetes is loss of sensation of the feet. This loss of
sensation is called diabetic peripheral neuropathy. Diabetic peripheral neuropathy is a
complication that can be expected in 60-70% of all cases of diabetes
mellitus. Many cases of diabetic peripheral neuropathy are asymptomatic.
Poorly
controlled diabetes mellitus results in long term exposure of the
peripheral nerve to elevated blood sugar levels. Elevated blood
sugar levels can affect peripheral nerves in a number of ways.
Elevated levels of blood glucose results in elevated levels of blood
borne toxins. These toxins tend to erode the outer sheath of the peripheral nerve, making
peripheral nerves more sensitive to
caustic body fluids. Many theories have been proposed to detail how long
standing diabetes mellitus effects the peripheral nerves. And none of
these theories are universally accepted. The most accepted
theory that has been proposed relates to elevated levels of sorbitol. Sorbital is a
by-product of the metabolism of glucose. Impaired metabolism of
glucose results in elevated levels of sorbital which is known to be
toxic to the peripheral nerves. As a general rule, peripheral
neuropathy is known to be caused by long term exposure to caustic
chemicals. Long
term exposure to sorbital is an established mechanism to describe the
onset of diabetic peripheral neuropathy.
Another factor that contributes to the onset of diabetic
peripheral neuropathy is decreased arterial circulation of the peripheral
nerves. Elevated blood glucose levels tend to affect arteries and
arterioles in a number of ways. Increased levels of blood glucose make the
blood viscous. The circulatory system has a difficult time pushing a
viscous fluid through the artery. As a result, the walls of the arteries
and arterioles become hard and less permeable to blood. Peripheral nerves
are significantly affected by this change. In the presence of high
circulating levels of blood glucose, peripheral nerves are essentially starved
of oxygen and essential nutrients and vitamins.
The symptoms
of diabetic neuropathy are described as a 'stocking and glove'
distribution, meaning that the symptoms affect the foot, leg and hand.
Most symptoms begin in the feet. Symptoms begin distally and progress proximally over time. The symptoms are described as a burning sensation and electrical shock
sensation that becomes worse at night or when a patient is not on their
feet.
Diabetics with advanced
peripheral neuropathy experience a loss of proprioception, or the
ability to determine where you are in relationship to the ground or
space. As a result, diabetics with peripheral neuropathy become
unsteady on their feet due to advanced loss of sensory and motor function. Falls are common which can result in
additional morbidity such as broken hips.
Diabetic with advanced peripheral neuropathy also experience loss
of motor control of the muscles that control the function of the feet.
It's important to remember that the task performed by peripheral nerves is to
mediate both sensory information and to coordinate muscle function. Loss
of muscle function also contributes to an increased tendency to falls.
The
diagnosis of diabetic peripheral neuropathy is often made based upon a history
and physical exam. In early stages of diabetic peripheral neuropathy,
patients are often unaware of why their feet feel numb. And since there is
no pain, many diabetic patients fail to seek care. A history and physical
exam of a diabetic patient should include vibratory testing, sharp dull
discrimination and testing of light touch of the feet. Each of these tests
help to define the location and extent of diabetic peripheral neuropathy.
Nerve conduction studies and electromyography are used to test the
response time of nerve and muscle. Delays in response time and the pattern
or distribution of sensory/motor loss, helps to define diabetic peripheral
neuropathy.
Epidermal (skin) nerve biopsies are another test used to diagnose
diabetic peripheral neuropathy. The total number of epidermal nerves decreases
with diabetic peripheral neuropathy. The skin biopsy serves as a means by
which nerve fibers can be counted. A decrease in nerve fiber counts
suggests advancing diabetic peripheral neuropathy. And increase in small
nerve fibers suggests a response to treatment. Epidermal nerve biopsies
are currently the most sensitive testing method that is used to screen for
diabetic peripheral neuropathy.
Treatment of diabetic peripheral neuropathy
The
single most important step to be taken in the treatment of diabetic peripheral
neuropathy is the elimination of the primary cause of the
neuropathy. In diabetes, the single most important issue
affecting diabetic peripheral neuropathy is serum glucose levels. Controlling the onset of
diabetic peripheral neuropathy is best managed by decreasing serum blood
sugar levels. Once the primary contributing factors are removed, the
nerve may have an opportunity to regenerate. Supportive efforts are
helpful during this phase of repair and include nutritional support and
the use of anti-oxidants. The following are some of the supportive
measures that can be used in the treatment of diabetic peripheral
neuropathy:
Pyridoxine
(B6) has been used for years as a method of nutritional support
following peripheral nerve damage. Vitamin B6 is water soluble and
can therefore be eliminated by your body. Common doses range as
high as 250mg/day.
Exciting new treatment
modalities for diabetic peripheral neuropathy includes the used of
anti-oxidants. These scavengers of the body are used to eliminate
toxins which may contribute to peripheral neuropathy.
Anti-oxidants used to treat peripheral neuropathy include gamma-linoleic
acid and alpha lipoic acid (thiotic acid). Alpha lipoic acid
increases glucose uptake in muscle and fat cells to improve both the
symptoms of diabetic peripheral neuropathy and diabetes. It has also been suggested the alpha
lipoic acid may help treat insulin resistance. A study by Tankova
et al. showed up to a 65% reduction in the symptoms of DPN with high
doses of alpha lipoic acid.
Other treatment may include
the use of metabolic factors or medications such as aldose reductase
inhibitors or aminogunidine. Autoimmune therapies and nerve growth
factors have also been tried. Oral dextromethorphan, a
N-methyl-D-aspartate (NMDA) receptor antagonist has also been used for
chronic peripheral neuritis. Dextromethorphan is widely available
over the counter in non-narcotic cough preparations such as RobitussinDM
and Benylin DM. It is believed that dextromethorphan has the
chemical ability to relieve peripheral neuritis pain by blocking pain
sensation. Studies have shown as much as a 24% reduction in
peripheral neuritis pain as compared to a placebo. Typical dosing
for these tests were 120mg/day or 3 tsp. every six hours with some
ranging up to 3 tbsp every six hours.
Mentanx is a prescription medical food supplement that is
used for dietary management of endothelia dysfunction in patients with
diabetic peripheral neuropathy. Mentanx increases nitric oxide
synthesis and offers the potential advantage of improving blood flow to
peripheral nerves. The literature shows an increase of 136% blood
flow to the peripheral nerves with the use of Mentanx over 8 weeks.
Mentanx is only approved for diabetic peripheral neuropathy.
The success of each of the modalities mentioned above can
be monitored with the use of periodic epidermal small nerve biopsies.
The epidermal small nerve biopsies can be performed in a matter of
minutes in your doctor's office using just a local anesthetic.
Advanced diabetic peripheral
neuropathy symptoms often produce severe pain. These symptoms are
described as electrical sharp shooting pains, burning pain and tingling
pain. For many patients, these symptoms are tolerable during the day but become severe at night often limiting the normal sleep
cycle. Neurontin (gabapentin) is a medication frequently used to suppress the
symptoms of diabetic peripheral neuropathy. Neurontin was originally
developed to control seizure disorders such as epilepsy. Neurontin
can be taken in divided doses during the day or in a single does at
bedtime. It is best to titrate Neurontin based upon the degree of
symptoms. Normal daily doses range from 300mg to
2400mg. Although the use of Neurontin for the control of symptoms
due to diabetic peripheral neuropathy is considered an 'off-label' use by The Food And Drug
Administration, doctors use it regularly for control of symptoms.
Cymbalta (duloxetine hydrocholride) was introduced by Eli Lilly Co. Cymbalta is a selective serotonin and
norepinephrine reuptake inhibitor (SSNRI) used for the treatment of pain and
depression associated with diabetic peripheral neuropathy. Cymbalta is FDA
approved for control of the symptoms of diabetic peripheral neuropathy. Cymbalta has been found in
studies to be safe and effective. Dosage for Cymbalta is usually between
60-120 mg daily.
Lyrica (pregabalin) is a new generation of
gabapentin introduced by Pfizer in 2004. Lyrica is also approved by The
FDA for the treatment of symptoms secondary to diabetic peripheral neuropathy. The exact mechanism of
action is not fully understood, but the presumed action is that pregabalin binds
with the alpha2-delta subunit of protein of calcium channels and acts to reduce
the release of excitatory neurotransmitters. Lyrica also has been shown in
clinical testing to be safe and effective.
Other medications for advanced diabetic peripheral
neuropathy include antidepressants such as Elavil. One of the side
effects of Elavil and its' related family of medications is
drowsiness. This side effect can be helpful in restoring the
normal sleep cycle in patients who suffer from painful peripheral
neuropathy symptoms.
Topical medications that can be used to sooth the pain of
peripheral neuropathy include
Biofreeze and
Neuragen PN.
Surgical decompression of peripheral nerves may be used to treat
diabetic peripheral neuropathy. This technique is called external
neurolysis. How does external neurolysis help diabetic peripheral
neuropathy? One school of though believes that elevated levels of glucose
tend to draw water into the nerve. As the sugar content within the nerve
increases, water is drawn in as an osmotic gradient. Increased
intra-neural pressure that results from this osmotic gradient, places pressure
on the nerve resulting in diabetic peripheral neuropathy. This internal
pressure is called crush syndrome. External neurolysis relieves this
pressure, restoring normal function to the nerve.
The following images show what is called a triple crush release (3
separate compressed nerves). The first row of images show external
neurolysis of the deep peroneal nerve. The second row shows surgical
external neurolysis of the posterior tibial nerve. And the third row shows
external neurolysis of the common peroneal nerve, lateral aspect of the knee.
