Diabetic Neuropathy

Diabetic neuropathy is a neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum) in addition to macrovascular conditions that can culminate in diabetic neuropathy.


         Nerve damage caused by diabetes mellitus can also lead to future 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, diabetic neuropathy can flare up suddenly, causing weakness and weight loss. Depression may follow.


Signs and symptoms of Diabetic Neuropathy

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Diabetic neuropathy affects all peripheral nerves including pain fibers, motor neurons and the autonomic nervous system. It therefore can affect all organs and systems, as all are innervated. There are several distinct syndromes based upon the organ systems and members affected, but these are by no means exclusive. A patient can have sensorimotor and autonomic neuropathy or any other combination. Symptoms vary depending on the nerve(s) affected and may include symptoms other than those listed. Symptoms usually develop gradually over years.


Symptoms may include:

  • Numbness and tingling of extremities
  • Dysesthesia (abnormal sensation to a body part)
  • Diarrhea
  • Erectile dysfunction
  • Urinary incontinence (loss of bladder control)
  • Facial, mouth and eyelid drooping
  • Vision changes
  • Dizziness
  • Muscle weakness
  • Difficulty swallowing
  • Speech impairment
  • Fasciculation (muscle contractions)
  • Anorgasmia
  • Burning or electric pain


Causes of Diabetic Neuropathy


          Unfortunately, researchers and doctors do not really know what causes diabetic neuropathy, but several factors are likely to contribute to the disorder. High blood glucose, a condition associated with diabetes mellitus, causes chemical changes in nerves. These changes impair nerves abilities 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 mellitus 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 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 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 mellitus, 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. Researchers are studying how these changes occur, how they are connected, how they cause nerve damage, and how to prevent and treat damage.


People with diabetes mellitus can develop nerve problems at any time. Significant clinical diabetic neuropathy can develop within the first 10 years after diagnosis of diabetes mellitus and the risk of developing diabetic neuropathy increases the longer a person has diabetes mellitus. Some recent studies have reported that 60 percent of patients with diabetes mellitus have some form of neuropathy, but in most cases (30 to 40 percent) there are no symptoms. Approx' 30 to 40 percent of patients with diabetes mellitus have symptoms suggesting neuropathy, compared with only 10 percent of people without diabetes mellitus. Diabetic neuropathy appears to be more common in smokers, people over age 40, and those who have had problems controlling their blood glucose levels.


Major Types Of Diabetic Neuropathy

Diffuse Neuropathy

          Diffuse neuropathy is a kind of nerve problem that affects many parts of the body. There are two types of diffuse neuropathy. Peripheral neuropathy affects the feet and hands and autonomic neuropathy affects the internal organs. Autonomic neuropathy can affect a lot of body processes and systems, everything from sexual response in both women and men, digestive problems that cause weight loss, even regulation of body temperature and sweat.

Focal Neuropathy

          This kind of diabetic neuropathy appears suddenly and affects specific nerves, most often in the torso, leg or head. Symptoms can include severe pain in an area of the body, eye and hearing problems or even paralysis on one side of the face called Bell's palsy. Carpel tunnel syndrome is a common symptom of focal neuropathy. This type of diabetic neuropathy is unpredictable and most often occurs in older people who have mild diabetes mellitus. Although it's painful, it tends to improve by itself without causing long-term damage.


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 peripheral neuropathy are:



  • Numbness or insensitivity to pain or temperature
  • Tingling, burning, or prickling
  • Sharp pains or cramps
  • Extreme sensitivity to touch, even light touch
  • Loss of balance and coordination.

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 mellitus can also lead to a gradual loss of sexual response in both men and women, although sex drive is unchanged.


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

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

  • Pain in the front of a thigh 
  • Severe pain in the lower back or pelvis 
  • Pain in the chest, stomach, or flank 
  • Chest or abdominal pain sometimes mistaken for angina, heart attack, or appendicitis 
  • Aching behind an eye 
  • Inability to focus the eye 
  • Double vision 
  • Paralysis on one side of the face (Bell's palsy) 
  • Problems with hearing



          This kind of diabetic neuropathy is unpredictable and occurs most often in older people who have mild diabetes mellitus. Although focal neuropathy can be painful, it tends to improve by itself after a period of weeks or months without causing long-term damage.


          People with diabetes mellitus are also prone to developing compression neuropathies. The most common form of compression neuropathy is carpal tunnel syndrome. Asymptomatic carpal tunnel syndrome occurs in 20 to 30 percent of people with diabetes mellitus, and symptomatic carpal tunnel syndrome occurs in 6 to 11 percent. Numbness and tingling of the hand are the most common symptoms. Muscle weakness may also develop.


Diagnosis of Diabetic Neuropathy

          A doctor diagnoses diabetic 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.


Treatment of Diabetic Neuropathy

Despite advances in the understanding of the metabolic causes of diabetic neuropathy, treatments aimed at interrupting these pathological processes have been limited. Thus, with the exception of tight glucose control, treatments are for reducing pain and other symptoms.
Options for pain control include tricyclic antidepressants (TCAs), serotonin reuptake inhibitors (SSRIs) and antiepileptic drugs (AEDs). A systematic review concluded that "tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief than newer generation anticonvulsants." A combination of these medication (gabapentin + nortriptyline) may also be superior to a single agent.
The only two drugs approved by the FDA for diabetic peripheral diabetic neuropathy are the antidepressant duloxetine and the anticonvulsant pregabalin. Before trying a systemic medication, some doctors recommend treating localized diabetic periperal diabetic neuropathy with lidocaine patches.


Tricyclic antidepressants

TCAs include imipramine, amitriptyline, desipramine and nortriptyline. These drugs are effective at decreasing painful symptoms but suffer from multiple side effects that are dosage dependent. One notable side effect is cardiac toxicity, which can lead to fatal arrhythmias. At low dosages used for diabetic neuropathy, toxicity is rare, but if symptoms warrant higher doses, complications are more common. Among the TCAs, amitriptyline is most widely used for this condition, but desipramine and nortriptyline have fewer side effects.


Serotonin-norepinephrine reuptake inhibitors

The SSNRI duloxetine (Cymbalta) is approved for diabetic neuropathy, while venlafaxine is also commonly used. By targeting both serotonin and norepinephrine, these drugs target the painful symptoms of diabetic neuropathy, and also treat depression if it exists. On the other hand, selective serotonin reuptake inhibitors are not useful.


Selective Serotonin reuptake inhibitor

SSRIs include fluoxetine, paroxetine, sertraline and citalopram and are not recommended to treat painful diabetic neuropathy because they have been found to be no more efficacious than placebo in several controlled trials. Side effects are rarely serious, and do not cause any permanent disabilities. They cause sedation and weight gain, which can worsen a diabetic's glycemic control. They can be used at dosages that also relieve the symptoms of depression, a common comorbidity of diabetic neuropathy.


Antiepileptic drugs

AEDs, especially gabapentin and the related pregabalin, are emerging as first line treatment for painful diabetic neuropathy. Gabapentin compares favorably with amitriptyline in terms of efficacy, and is clearly safer. Its main side effect is sedation, which does not diminish over time and may in fact worsen. It needs to be taken three times a day, and it sometimes causes weight gain, which can worsen glycemic control in diabetics. Carbamazepine (Tegretol) is effective but not necessarily safe for diabetic neuropathy. Its first metabolite, oxcarbazepine, is both safe and effective in other neuropathic disorders, but has not been studied in diabetic neuropathy. Topiramate has not been studied in diabetic neuropathy, but has the beneficial side effect of causing mild anorexia and weight loss, and is anecdotally beneficial. Clinical studies have differed regarding its effectiveness; improved diabetic control may improve this.


Classic analgesics

The above three categories of drugs fall under the heading of "atypical, adjuvant and potentiators" and are often combined with opioids and/or NSAIDs, usually having effects greater than the sum of their parts.
Duloxetine + extended release morphine ± naproxen ± hydroxyzine (esp. with oxycodone) ± morphine or hydromorphone immediate release for breakthrough pain is a common recipe in cases where diabetic neuropathy is a complicating factor in a debilitating chronic pain condition — amitryptiline may be more effective than Duloxetine in some. Opioids requiring Cytochrome P-450 activation (e.g. codeine, dihydrocodeine) should perhaps be used with an agent not chemically related to the SSRIs; conversely, they may impact parts of the Liberation, Absorption, Distribution, Metabolism & Elimination profile for morphine, hydromorphone, oxymorphone &c the other way.


Physical therapy

Physical therapy can be an effective and alternative treatment option for patients with diabetes mellitus. This may help reduce dependency on pain relieving drug therapies. Certain physiotherapy techniques can help alleviate symptoms brought on from diabetic neuropathy such as deep pain in the feet and legs, tingling or burning sensation in extremities, muscle cramps, muscle weakness, sexual dysfunction, and diabetic foot.
Transcutaneous electrical nerve stimulation (TENS) and interferential current (IFC) use a painless electric current and the physiological effects from low frequency electrical stimulation to relieve stiffness, improve mobility, relieve neuropathic pain, reduce oedema, and heal resistant foot ulcers.
Gait training, posture training, and teaching these patients the basic principles of off-loading can help prevent and/or stabilize foot complications such as foot ulcers. Off-loading techniques can include the use of mobility aids (e.g. crutches) or foot splints. Gait re-training would also be beneficial for individuals who have lost limbs, due to diabetic neuropathy, and now wear a prosthesis.
Exercise programs, along with manual therapy, will help to prevent muscle contratures, spasms and atrophy. These programs may include general muscle stretching to maintain muscle length and a person’s range of motion.General muscle strengthening exercises will help to maintain muscle strength and reduce muscle wasting. Aerobic exercise such as swimming and using a stationary bicycle can help peripheral diabetic neuropathy, but activities that place excessive pressure on the feet (e.g. walking long distances, running) may be contraindicated.
Heat, therapeutic ultrasound, hot wax and short wave diathermy are also useful for treating diabetic neuropathy. Pelvic floor muscle exercises can improve sexual dysfunction caused by diabetic neuropathy.

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