- What is diabetic neuropathy
- Types of diabetic neuropathy
- Diabetic peripheral neuropathy
- Diabetic autonomic neuropathy
- Additional types of diabetic neuropathy
- Can diabetic neuropathy be reversed?
- Diabetic neuropathy potential complications
- Diabetic neuropathy causes
- Diabetic neuropathy prevention
- Diabetic neuropathy signs and symptoms
- Diabetic neuropathy diagnosis
- Diabetic neuropathy treatment
- Types of diabetic neuropathy
What is diabetic neuropathy
Diabetic neuropathy is a type of nerve damage in people either with type 1 or type 2 diabetes; up to 26 percent of people with type 2 diabetes have evidence of nerve damage at the time that diabetes is diagnosed 1). About half of all people with diabetes have some form of diabetic neuropathy. It is more common in those who have had the disease for a number of years and can lead to many kinds of problems.
More than 60 percent of all nontraumatic lower-limb amputations in the United States occur in people with diabetes. Nontraumatic amputations are those not caused by trauma such as severe injuries from an accident. In 2004, about 71,000 nontraumatic amputations were performed in people with diabetes. Comprehensive foot care programs can reduce amputation rates by 45 to 85 percent.
You have three types of nerves:
- Sensory nerves carry signals about touch, taste, sight, hearing and smell
- Motor nerves carry signals to help you move
- Autonomic nerves carry signals to help with balance, sweating, digestion and many of the things you do without thinking.
Diabetic neuropathy often affects sensory nerves to the feet and hands, but can also affect both the autonomic and motor nerves. A generalized type of neuropathy, known as polyneuropathy, is the most common type of diabetic neuropathy. Your feet or hands might feel numb, tingly or painful.
Diabetic peripheral neuropathy increases the risk for foot ulcers and amputation. Due to nerve damage in their feet and toes, people with diabetes who have diabetic peripheral neuropathy often do not notice minor cuts, sores, or blisters in these areas. If left untreated, these small wounds can easily become infected, lead to gangrene, and may eventually require amputation of the affected area.
Diabetic neuropathy is probably caused by high levels of glucose in your blood damaging the tiny blood vessels that supply your nerves.
If you keep your blood glucose levels on target, you may help prevent or delay nerve damage. If you already have nerve damage, this will help prevent or delay further damage. There are also other treatments that can help.
Peripheral neuropathy becomes more likely the longer you’ve had diabetes. Up to one in every four people with the condition experience some loss of sensation and/or burning pain in their feet caused by nerve damage.
Early detection of diabetes and tight control of blood sugar levels may reduce the risk of developing diabetic neuropathy.
Treatments for diabetic neuropathy are available, and include several elements: control of blood glucose levels, prevention of injury, and control of painful symptoms.
If you have diabetes, your risk of polyneuropathy is higher if your blood sugar is poorly controlled or you:
- regularly consume large amounts of alcohol
- are over 40 years old
If you have diabetes, you should examine your own feet regularly to check for ulcers (open wounds or sores) or chilblains.
Types of diabetic neuropathy
Diabetic peripheral neuropathy
Diabetic peripheral neuropathy can cause tingling, pain, numbness, or weakness in your feet and hands.
Peripheral neuropathy is the most common form of diabetic neuropathy. Your feet and legs are often affected first, followed by your hands and arms.
Peripheral neuropathy, also called distal symmetric neuropathy or sensorimotor neuropathy, is nerve damage in the arms and legs. Feet and legs are likely to be affected before hands and arms. Many people with diabetes have signs of neuropathy that a doctor could note but feel no symptoms themselves.
Peripheral neuropathy may also cause muscle weakness and loss of reflexes, especially at the ankle, leading to changes in the way a person walks. Foot deformities, such as hammertoes and the collapse of the midfoot, may occur. Blisters and sores may appear on numb areas of the foot because pressure or injury goes unnoticed. If an infection occurs and is not treated promptly, the infection may spread to the bone, and the foot may then have to be amputated. Many amputations are preventable if minor problems are caught and treated in time.
Symptoms of peripheral neuropathy may include:
- numbness or insensitivity to pain or temperature
- a tingling, burning, or prickling sensation
- sharp pains or cramps
- extreme sensitivity to touch, even light touch
- loss of balance and coordination
These symptoms are often worse at night.
Peripheral neuropathy affects
Signs and symptoms of peripheral neuropathy are often worse at night, and may include:
- Your feet tingle.
- You feel “pins and needles” in your feet.
Pain or Increased Sensitivity
- You have burning, stabbing or shooting pains in your feet.
- Your feet are very sensitive to touch. For example, sometimes it hurts to have the bed covers touch your feet.
- Sometimes you feel like you have socks or gloves on when you don’t.
- Your feet hurt at night.
- Your feet and hands get very cold or very hot.
Numbness or Weakness
- Your feet are numb and feel dead.
- You don’t feel pain in your feet, even when you have blisters or injuries.
- You can’t feel your feet when you’re walking.
- The muscles in your feet and legs are weak.
- You’re unsteady when you stand or walk.
- You have trouble feeling heat or cold in your feet or hands.
- It seems like the muscles and bones in your feet have changed shape.
- You have open sores (also called ulcers) on your feet and legs. These sores heal very slowly.
Preventing and treating diabetic peripheral neuropathy
Whether you’re trying to prevent diabetic neuropathy, or trying to stop it getting worse, the most important thing to do is to control your blood sugar levels. That means:
- sorting out any medical problems (with the help of your doctor if necessary)
- following the right diet for you
- exercising regularly
- taking or using any medication prescribed
- avoiding things that can cause problems, such as smoking and excessive drinking.
If you have diabetic neuropathy, discuss with your doctor or diabetes nurse how to protect your skin and deal with pain. The usual pain relief, such as paracetamol and ibuprofen, might not work with the pain of diabetic neuropathy. If so, talk to your doctor about other forms of pain relief.
Diabetic autonomic neuropathy
Autonomic neuropathy affects the autonomic nerves, which control the bladder, intestinal tract, and genitals, among other organs.
Paralysis of the bladder is a common symptom of this type of neuropathy. When this happens, the nerves of the bladder no longer respond normally to pressure as the bladder fills with urine. As a result, urine stays in the bladder, leading to urinary tract infections.
Autonomic neuropathy can also cause erectile dysfunction (ED) when it affects the nerves that control erection with sexual arousal. However, sexual desire does not usually decrease.
Diarrhea can occur when the nerves that control the small intestine are damaged. The diarrhea occurs most often at night. Constipation is another common result of damage to nerves in the intestines.
Sometimes, the stomach is affected. It loses the ability to move food through the digestive system, causing vomiting and bloating. This condition, called gastroparesis, can change how fast the body absorbs food. It can make it hard to match insulin doses to food portions.
Scientists do not know the precise cause of autonomic neuropathy and are looking for better treatments for his type of neuropathy.
Diabetic autonomic neuropathy symptoms
This type of nerve damage affects the nerves in your body that control your body systems. It affects your digestive system, urinary tract, sex organs, heart and blood vessels, sweat glands, and eyes. Look at the list below and make a note about any symptoms you have. Bring this list to your next office visit.
Your digestive system
- You get indigestion or heartburn.
- You get nauseous and you vomit undigested food.
- It seems like food sits in your stomach instead of being digested.
- You feel bloated after you eat.
- Your stomach feels full, even after you eat only a small amount.
- You have diarrhea.
- You have lost control of your bowels.
- You get constipated.
- Your blood glucose levels are hard to predict. You never know if you’ll have high or low blood glucose after eating.
Nerve damage to the digestive system most commonly causes constipation. Damage can also cause the stomach to empty too slowly, a condition called gastroparesis. Severe gastroparesis can lead to persistent nausea and vomiting, bloating, and loss of appetite. Gastroparesis can also make blood glucose levels fluctuate widely, due to abnormal food digestion.
Nerve damage to the esophagus may make swallowing difficult, while nerve damage to the bowels can cause constipation alternating with frequent, uncontrolled diarrhea, especially at night. Problems with the digestive system can lead to weight loss.
Your urinary tract
- You have had bladder control problems, such as urinating very often or not often enough, feeling like you need to urinate when you don’t, or leaking urine.
- You don’t feel the need to urinate, even when your bladder is full.
- You have lost control of your bladder.
- You have frequent bladder infections.
Autonomic neuropathy often affects the organs that control urination and sexual function. Nerve damage can prevent the bladder from emptying completely, allowing bacteria to grow in the bladder and kidneys and causing urinary tract infections. When the nerves of the bladder are damaged, urinary incontinence may result because a person may not be able to sense when the bladder is full or control the muscles that release urine.
Your sex organs
- (For men) When you have sex, you have trouble getting or keeping an erection.
- (For women) When you have sex, you have problems with orgasms, feeling aroused, or you have vaginal dryness.
Autonomic neuropathy can also gradually decrease sexual response in men and women, although the sex drive may be unchanged. A man may be unable to have erections or may reach sexual climax without ejaculating normally. A woman may have difficulty with arousal, lubrication, or orgasm.
Your heart and blood vessels
- You get dizzy if you stand up too quickly.
- You have fainted after getting up or changing my position.
- You have fainted suddenly for no reason.
- At rest, your heart beats too fast.
- You had a heart attack but you didn’t have the typical warning signs such as chest pain.
The heart and blood vessels are part of the cardiovascular system, which controls blood circulation. Damage to nerves in the cardiovascular system interferes with the body’s ability to adjust blood pressure and heart rate. As a result, blood pressure may drop sharply after sitting or standing, causing a person to feel light-headed or even to faint. Damage to the nerves that control heart rate can mean that the heart rate stays high, instead of rising and falling in response to normal body functions and physical activity.
Your body’s warning system for low blood glucose levels (hypoglycemia)
- You used to get nervous and shaky when your blood glucose was getting too low, but you no longer have those warning signals.
Normally, symptoms such as shakiness, sweating, and palpitations occur when blood glucose levels drop below 70 mg/dL. In people with autonomic neuropathy, symptoms may not occur, making hypoglycemia difficult to recognize. Problems other than neuropathy can also cause hypoglycemia unawareness.
Your sweat glands
- You sweat a lot, especially at night or while you’re eating.
- You no longer sweat, even when you’re too hot.
- The skin on your feet is very dry.
Autonomic neuropathy can affect the nerves that control sweating. When nerve damage prevents the sweat glands from working properly, the body cannot regulate its temperature as it should. Nerve damage can also cause profuse sweating at night or while eating.
- It’s hard for your eyes to adjust when you go from a dark place into a bright place or when driving at night.
Finally, autonomic neuropathy can affect the pupils of the eyes, making them less responsive to changes in light. As a result, a person may not be able to see well when a light is turned on in a dark room or may have trouble driving at night.
Diabetic autonomic neuropathy diagnosis
To diagnose this kind of nerve damage, you will need a physical exam and special tests as well. For example, an ultrasound test uses sound waves to check on your bladder. Stomach problems can be found using x-rays and other tests. Reporting your symptoms plays a big part in making a diagnosis.
Diabetic autonomic neuropathy treatment
There are a number of treatments for damage to nerves that control body systems. For example, a dietitian can help you plan meals if you have nausea or feel full after eating a small amount. Some medications can speed digestion and reduce diarrhea. Problems with erections can be treated with medications or devices.
Additional types of diabetic neuropathy
Charcot’s Joint, also called neuropathic arthropathy, occurs when a joint breaks down because of a problem with the nerves. This type of neuropathy most often occurs in the foot.
In a typical case of Charcot’s Joint, the foot has lost most sensation. The person no longer can feel pain in the foot and loses the ability to sense the position of the joint. Also, the muscles lose their ability to support the joint properly. The foot then becomes unstable, and walking just makes it worse.
An injury, such as a twisted ankle, may make things even worse. Joints grind on bone. The result is inflammation, which leads to further instability and then dislocation. Finally, the bone structure of the foot collapses. Eventually, the foot heals on its own, but because of the breakdown of the bone, it heals into a deformed foot.
People at risk for Charcot’s Joint are those who already have neuropathy. They should be aware of symptoms such as:
- strong pulse
- insensitivity of the foot.
Early treatment can stop bone destruction and aid healing.
Cranial neuropathy affects the 12 pairs of nerves that are connected with the brain and control sight, eye movement, hearing, and taste.
Most often, cranial neuropathy affects the nerves that control the eye muscles. The neuropathy begins with pain on one side of the face near the affected eye. Later, the eye muscle becomes paralyzed. Double vision results. Symptoms of this type of neuropathy usually get better or go away within 2 or 3 months.
Compression mononeuropathy occurs when a single nerve is damaged. It is a fairly common type of neuropathy. There seem to be two kinds of damage. In the first, nerves are squashed at places where they must pass through a tight tunnel or over a lump of bone. Nerves of people with diabetes are more prone to compression injury. The second kind of damage arises when blood vessel disease caused by diabetes restricts blood flow to a part of the nerve.
Carpal tunnel syndrome is probably the most common compression mononeuropathy. It occurs when the median nerve of the forearm is compressed at the wrist. Symptoms of this type of neuropathy include numbness, swelling, or prickling in the fingers with or without pain when driving a car, knitting, or resting at night. Simply hanging your arm by your side usually stops the pain within a few minutes. If the symptoms are severe, an operation can give complete relief from pain.
Femoral neuropathy occurs most often in people with type 2 diabetes. A pain may develop in the front of one thigh. Muscle weakness follows, and the affected muscles waste away. A different kind of neuropathy that also affects the legs is called diabetic amyotrophy. In this case, weakness occurs on both sides of the body, but there is no pain. Doctors do not understand why it occurs, but blood vessel disease may be the cause.
Diabetic amyotrophy (radiculoplexus neuropathy)
Radiculoplexus neuropathy affects nerves in the thighs, hips, buttocks or legs. Also called diabetic amyotrophy, femoral neuropathy or proximal neuropathy, this condition is more common in people with type 2 diabetes and older adults.
Symptoms are usually on one side of the body, though in some cases symptoms may spread to the other side. Most people improve at least partially over time, though symptoms may worsen before they get better. This condition is often marked by:
- Sudden, severe pain in your hip and thigh or buttock
- Eventual weak and atrophied thigh muscles
- Difficulty rising from a sitting position
- Abdominal swelling, if the abdomen is affected
- Weight loss
Focal Neuropathy affects a nerve or group of nerves causing sudden weakness or pain. Focal neuropathy often comes on suddenly. It’s most common in older adults. It can lead to double vision, a paralysis on one side of the face called Bell’s palsy, or a pain in the front of the thigh or other parts of the body.
Focal neuropathy may cause
- inability to focus the eye
- double vision
- aching behind one eye
- paralysis on one side of the face, called Bell’s palsy
- severe pain in the lower back or pelvis
- pain in the front of a thigh
- pain in the chest, stomach, or side
- pain on the outside of the shin or inside of the foot
- chest or abdominal pain that is sometimes mistaken for heart disease, a heart attack, or appendicitis
Focal neuropathy is painful and unpredictable and occurs most often in older adults with diabetes. However, it tends to improve by itself over weeks or months and does not cause long-term damage.
People with diabetes also tend to develop nerve compressions, also called entrapment syndromes. One of the most common is carpal tunnel syndrome, which causes numbness and tingling of the hand and sometimes muscle weakness or pain. Other nerves susceptible to entrapment may cause pain on the outside of the shin or the inside of the foot.
Thoracic or lumbar radiculopath is another common mononeuropathy. It is like femoral neuropathy, except that it occurs in the torso. It affects a band of the chest or abdominal wall on one or both sides. It seems to occur more often in people with type 2 diabetes. Again, people with this neuropathy get better with time.
Unilateral Foot Drop
Unilateral foot drop is when the foot can’t be picked up. It occurs from damage to the peroneal nerve of the leg by compression or vessel disease. Foot drop can improve.
Can diabetic neuropathy be reversed?
There’s a lot you can do to prevent or delay diabetic neuropathy. And, if you already have diabetic neuropathy (nerve damage), these steps can prevent or delay further damage and may lessen your symptoms.
Keep Your Blood Glucose Levels in Your Target Range
Experts reviewed nearly 200 studies involving thousands of people with diabetes, examining their treatment regimens 2). They found that intensive blood glucose management seems to prevent amputations. The downside: There was no effect on foot ulcers. However, specific types of footwear, home monitoring of foot skin temperature, and certain surgeries can prevent foot ulcers. Better still, remember to inspect your feet daily for early warning signs of ulcers so you can seek treatment.
Meal planning, physical activity and medications, if needed, all can help you reach your target range. There are two ways to keep track of your blood glucose levels:
- Use a blood glucose meter to help you make decisions about day-to-day care.
- Get an A1C test (a lab test) at least twice a year to find out your average blood glucose for the past 2 to 3 months.
Checking your blood glucose levels will tell you whether your diabetes care plan is working or whether changes are needed.
- Report symptoms of diabetic neuropathy.
- If you have problems, get treatment right away. Early treatment can help prevent more problems later on. For example, if you take care of a foot infection early, it can help prevent amputation.
- Take good care of your feet. Check your feet every day. If you no longer can feel pain in your feet, you might not notice a foot injury. Instead, use your eyes to look for problems. Use a mirror to see the bottoms of your feet. Use your hands to feel for hot or cold spots, bumps or dry skin. Look for sores, cuts or breaks in the skin. Also check for corns, calluses, blisters, red areas, swelling, ingrown toenails and toenail infections. If it’s hard for you to see or reach your feet, get help from a family member or foot doctor.
- Protect your feet. If your feet are dry, use a lotion on your skin but not between your toes. Wear shoes and socks that fit well and wear them all the time. Use warm water to wash your feet, and dry them carefully afterward.
- Get special shoes if needed. If you have foot problems, Medicare may pay for shoes. Ask your health care team about it.
- Be careful with exercising. Some physical activities are not safe for people with neuropathy. Talk with a diabetes clinical exercise expert who can guide you.
Screening for diabetic neuropathy
For type 1 diabetes
- Because diabetic peripheral neuropathy is uncommon within the first five years after onset of type 1 diabetes, annual screening for diabetic peripheral neuropathy should begin after five years of diabetes diagnosis.
- For children with type 1 diabetes, screening should be done once the child is past puberty and has had diabetes for at least five years.
For type 2 diabetes
For people with type 2 diabetes, screening for diabetic peripheral neuropathy should begin right away, at diagnosis of diabetes, and every year after that.
Diabetic neuropathy potential complications
As you lose the ability to sense pain or hot and cold, your risk of injuring your feet increases. Injuries that would normally cause pain (e.g, stepping on a splinter, wearing shoes that create a blister, developing an ingrown toenail) do not necessarily cause pain if you have diabetic neuropathy. Unless you inspect your feet on a daily basis, a small injury has the potential to develop into a large ulcer. One of the most serious complications of foot ulcers is the need for amputation of a toe, or in extreme cases, the foot itself.
Diabetic neuropathy can cause a number of serious complications, including:
- Loss of a limb. Because nerve damage can cause a lack of feeling in your feet, cuts and sores may go unnoticed and eventually become severely infected or ulcerated — a condition in which the skin and soft tissues break down. The risk of infection is high because diabetes reduces blood flow to your feet. Infections that spread to the bone and cause tissue death (gangrene) may be impossible to treat and require amputation of a toe, foot or even the lower leg.
- Charcot joint. This occurs when a joint, usually in the foot, deteriorates because of nerve damage. Charcot joint is marked by loss of sensation, as well as swelling, instability and sometimes deformity in the joint itself. Early treatment can promote healing and prevent further damage.
- Urinary tract infections and urinary incontinence. Damage to the nerves that control your bladder can prevent it from emptying completely. This allows bacteria to multiply in your bladder and kidneys, leading to urinary tract infections. Nerve damage can also affect your ability to feel when you need to urinate or to control the muscles that release urine.
- Hypoglycemia unawareness. Normally, when your blood sugar drops too low — below 70 milligrams per deciliter (mg/dL), or 3.9 millimoles per liter (mmol/L) — you develop symptoms such as shakiness, sweating and a fast heartbeat. Autonomic neuropathy can interfere with your ability to notice these symptoms.
- Low blood pressure. Damage to the nerves that control circulation can affect your body’s ability to adjust blood pressure. This can cause a sharp drop in pressure when you stand after sitting (orthostatic hypotension), which may lead to dizziness and fainting.
- Digestive problems. Nerve damage in the digestive system can cause constipation or diarrhea — or alternating bouts of constipation and diarrhea — as well as nausea, vomiting, bloating and loss of appetite. It can also cause gastroparesis, a condition in which the stomach empties too slowly or not at all. This can interfere with digestion and cause nausea, vomiting and bloating, and severely affect blood sugar levels and nutrition.
- Sexual dysfunction. Autonomic neuropathy often damages the nerves that affect the sex organs, leading to erectile dysfunction in men and problems with lubrication and arousal in women.
- Increased or decreased sweating. When the sweat glands don’t function normally, your body isn’t able to regulate its temperature properly. A reduced or complete lack of perspiration (anhidrosis) can be life-threatening. Autonomic neuropathy may also cause excessive sweating, particularly at night or while eating.
How can I prevent complications of diabetic neuropathy?
Have a complete foot exam once a year. If you already have foot problems, have your feet checked more often. A complete foot exam includes a check of the skin on your feet, your foot muscles and bones, and your blood flow. Your provider will also check for numbness in your feet by touching your foot with a monofilament. It looks like a stiff piece of nylon fishing line or a bristle in a hairbrush.
Other ways to check your nerves include using a tuning fork. It may be touched to your foot to see if you can feel it moving.
Although there is no cure, there are many ways you can effectively manage diabetic peripheral neuropathy.
Proper foot care
- Examine your feet and legs daily.
- Care for you nails regularly.
- Apply lotion if your feet are dry (but not between the toes).
- Wear properly fitting footwear.
- Test your bath water before you step in to make sure it’s not too hot.
- Do not soak your feet.
Basic Steps to Foot Care
You should look for the following signs, comparing one foot to the other:
- A change in the size or shape of the foot
- A change in skin color (becoming red or blue)
- A change in skin temperature (warmer or cooler)
- An open area of skin (blister or sore) with or without drainage
- An ingrown toenail
- Structural deformities of the foot (hammer toes or bunions)
- Corns or calluses
- Pain, burning, tingling, or numbness in your feet
Acute changes should be promptly reported to your podiatrist or the doctor taking care of your diabetes. Regular professional foot care is advised for treatment of your calluses. Treating these conditions yourself is ill-advised. Daily use of an emollient (lotion) is helpful for dry skin care (and reminds you to look at your feet).
Selection of footwear should be appropriate for the occasion. Your feet should be measured and shoes should be properly fitted by an experienced shoe fitter. Athletic shoes are generally designed for specific sports activities. Make sure that your tennis shoes fit well, are comfortable, and are in good condition. Make sure to wear athletic socks. Socks made with a blend of acrylic and natural fibers are best for wicking moisture away from the skin.
An annual foot exam is recommended for identification of conditions that may require further investigation or treatment. Prevention of foot complications is the key objective. Amputation is not an inevitable consequence of diabetes.
How Can I Make My Shoes Fit Correctly?
Be a smart shoe shopper. Take your time selecting the proper shoes, and be sure to ask about the return policy. Most retailers realize that trying on a pair of shoes for a few minutes in a store may not provide the full story. The shoe store will often let you purchase the shoes, wear them at home for a couple of hours, and then, if necessary, return them for an exchange (provided they were not worn outside or otherwise dirtied).
Any evidence of redness or irritation on the foot is a sign you need a different size or style. Keep in mind: Size isn’t everything. Different styles of shoes may offer a radical difference in fit, even if they are measured as the same size. Knowing your size gets you in the ballpark. Be prepared to go up or down a size depending on how that particular shoe or sneaker fits.
Consulting with a podiatrist for a comprehensive foot exam can help you determine whether there are special considerations to take into account. A visit to a pedorthist, an expert in creating shoes, orthotics, and other devices to reduce foot problems, may also be helpful.
Special types of shoes, such as those with extra depth (to provide room for hammertoes) or with an expandable upper portion (to accommodate increasing swelling throughout the day), may be recommended. Custom-molded shoes may be required for those with more significant deformities. Shoes with a special type of insole known as Plastazote can be helpful in reducing pressure in the areas that have previously gotten ulcers or have the potential to do so.
Excellent blood glucose control
Managing your blood glucose levels effectively can help to prevent further nerve damage.
- Some medications that act on the nerves, can be helpful.
- Ask your doctor what would be best for you diabetes (see Diabetic neuropathy medications below).
Diabetic neuropathy causes
It seems that having high levels of sugar in the blood for a long time damages the nerves. High levels of triglycerides, a type of fat found in the blood, can also cause nerve damage.
Why this happens isn’t completely clear, but a combination of factors likely plays a role, including the complex interaction between nerves and blood vessels.
High blood sugar interferes with the ability of the nerves to transmit signals. It also weakens the walls of the small blood vessels (capillaries) that supply the nerves with oxygen and nutrients.
Researchers are studying how prolonged exposure to high blood glucose causes nerve damage. Nerve damage is likely due to a combination of factors:
- metabolic factors, such as high blood glucose, long duration of diabetes, abnormal blood fat levels, and possibly low levels of insulin
- neurovascular factors, leading to damage to the blood vessels that carry oxygen and nutrients to nerves
- autoimmune factors that cause inflammation in nerves
- mechanical injury to nerves, such as carpal tunnel syndrome
- inherited traits that increase susceptibility to nerve disease
- lifestyle factors, such as smoking or alcohol use
Other conditions can play a part, including:
- high blood pressure
- vitamin B deficiency
- alcohol abuse
- kidney disease or liver disease. Diabetes can cause damage to the kidneys, which may increase the toxins in the blood and contribute to nerve damage.
- some medicines, including some drugs used against cancer
- inflammation in the nerves caused by an autoimmune response. This occurs when your immune system mistakenly attacks part of your body as if it were a foreign organism.
- genetic factors unrelated to diabetes that make some people more susceptible to nerve damage.
The longer you have had diabetes, the more likely you are to develop diabetic neuropathy.
Diabetic neuropathy risk factors
In people with type 1 or type 2 diabetes, the biggest risk factor for developing diabetic neuropathy is having high blood sugar levels over time.
Other factors can further increase the risk of developing diabetic neuropathy, including:
- Coronary artery disease
- Increased triglyceride levels
- Being overweight (a body mass index or BMI >24). Having a body mass index greater than 24 may increase your risk of developing diabetic neuropathy.
- Smoking. Smoking narrows and hardens your arteries, reducing blood flow to your legs and feet. This makes it more difficult for wounds to heal and damages the integrity of the peripheral nerves.
- High blood pressure.
Diabetic neuropathy prevention
You can help prevent or delay diabetic neuropathy and its complications by keeping your blood sugar consistently well-controlled, taking good care of your feet and following a healthy lifestyle.
Blood sugar control
Keeping your blood sugar tightly controlled requires continuous monitoring and, if you take insulin, frequent doses of medication. But keeping your blood sugar consistently within your target range is the best way to help prevent neuropathy and other complications of diabetes. Consistency is important because shifts in blood sugar levels can accelerate nerve damage.
The American Diabetes Association recommends that people with diabetes have a blood test called the A1C test at least twice a year to find out your average blood sugar level for the past two to three months. If your blood sugar isn’t well-controlled or you change medications, you may need to get tested more often.
Foot problems, including sores that don’t heal, ulcers and even amputation, are a common complication of diabetic neuropathy. But you can prevent many of these problems by having a comprehensive foot exam at least once a year, having your doctor check your feet at each office visit and taking good care of your feet at home.
To protect the health of your feet:
- Check your feet every day. Look for blisters, cuts, bruises, cracked and peeling skin, redness and swelling. Use a mirror or ask a friend or family member to help examine parts of your feet that are hard to see.
- Keep your feet clean and dry. Wash your feet every day with lukewarm water and mild soap. Avoid soaking your feet. Dry your feet and between your toes carefully by blotting or patting with a soft towel.Moisturize your feet thoroughly to prevent cracking. Avoid getting lotion between your toes, however, as this can encourage fungal growth.
- Trim your toenails carefully. Cut your toenails straight across, and file the edges carefully so there are no sharp edges.
- Wear clean, dry socks. Look for socks made of cotton or moisture-wicking fibers that don’t have tight bands or thick seams.
- Wear cushioned shoes that fit well. Always wear shoes or slippers to protect your feet from injury. Make sure that your shoes fit properly and allow your toes to move. A podiatrist can teach you how to buy properly fitted shoes and to prevent problems such as corns and calluses.If problems do occur, your doctor can help treat them to prevent more-serious conditions. Even small sores can quickly turn into severe infections if left untreated.If you qualify for Medicare, your plan may cover the cost of at least one pair of shoes each year. Talk to your doctor or diabetes educator for more information.
Diabetic neuropathy signs and symptoms
The most common symptoms of diabetic neuropathy are sharp-shooting pain, burning, tingling, or numbness sensation, aching, cramps, throbbing and weakness in the toes or feet, and extreme sensitivity to light touch. Most people find symptoms usually begin in their hands or feet. These symptoms may later spread to their arms and legs. The pain may be worst at rest and improve with activity, such as walking. Some people initially have intensely painful feet while others have few or no symptoms.
Diabetic neuropathy usually affects both sides of the body. Symptoms are usually noticed first in the toes. If the disease progresses, symptoms may gradually move up the legs; if the mid-calves are affected, symptoms may develop in the hands. Over time, the ability to sense pain may be lost, which greatly increases the risk of injury.
Diabetic neuropathy can also cause:
- pain and discomfort in yours arms or legs, especially at night
- sleep problems
- bloating and digestion
- heat intolerance
- problems with walking.
Diabetic neuropathy diagnosis
Diabetic neuropathy is diagnosed based upon a medical history and physical examination of the feet.
Your doctor or foot care specialist can test for diabetic peripheral neuropathy by lightly pressing a thin nylon rod (10-gram monofilament) to different areas of your foot (in particular, your big toe) or by using the 128-Hz tuning fork on the back of the big toe to determine if you can feel it. These are easy and pain-free tests.
During an examination, there may be signs of nerve injury, including:
- Loss of the ability to sense vibration and movement in the toes or feet (eg, when the toe is moved up or down)
- Loss of the ability to sense pain, light touch and temperature in the toes or feet
- Loss or reduction of the Achilles tendon reflex
More extensive testing, including nerve conduction studies and electromyography (EMG), nerve biopsy, or imaging tests (e.g, x-ray or CT scan), is not usually needed to diagnose diabetic neuropathy.
However, if the doctor thinks you might have nerve damage, you may have tests that look at how well the nerves in your arms and legs are working. Nerve conduction studies check the speed with which nerves send messages. An EMG checks how your nerves and muscles work together.
- Electromyography (EMG). Often performed along with nerve conduction studies, electromyography measures the electrical discharges produced in your muscles.
- Quantitative sensory testing. This noninvasive test is used to assess how your nerves respond to vibration and changes in temperature.
- Autonomic testing. If you have symptoms of autonomic neuropathy, your doctor may request special tests to look at your blood pressure in different positions and assess your ability to sweat.
The doctor may perform other tests as part of the diagnosis.
- Nerve conduction studies or electromyography are sometimes used to help determine the type and extent of nerve damage. Nerve conduction studies check the transmission of electrical current through a nerve. Electromyography shows how well muscles respond to electrical signals transmitted by nearby nerves. These tests are rarely needed to diagnose neuropathy.
- A check of heart rate variability shows how the heart responds to deep breathing and to changes in blood pressure and posture.
- Ultrasound uses sound waves to produce an image of internal organs. An ultrasound of the bladder and other parts of the urinary tract, for example, can be used to assess the structure of these organs and show whether the bladder empties completely after urination.
The American Diabetes Association recommends that all people with diabetes have a comprehensive foot exam — either by a doctor or by a foot specialist (podiatrist) — at least once a year. In addition, your feet should be checked for sores, cracked skin, calluses, blisters, and bone and joint abnormalities at every office visit.
Diabetic neuropathy treatment
There are three main components of diabetic neuropathy treatment:
- Tight control of blood sugar levels
- Care for the feet to prevent complications
- Control of pain caused by neuropathy
Although there is no cure for diabetic neuropathy, use of these treatments can improve painful symptoms and prevent complications.
Control blood sugar levels — One of the most important treatments for diabetic neuropathy is to control blood sugar levels. Symptoms of pain and burning may improve when blood glucose sugar improves.
Slowing progression of the diabetic neuropathy
Consistently keeping blood sugar within a target range can help prevent or delay the progression of diabetic neuropathy and may even improve some of the symptoms you already have. Your doctor will determine the best target range for you based on several factors, such as your age, how long you’ve had diabetes, and your overall health and the presence of other medical conditions.
For many people who have diabetes, Mayo Clinic generally recommends target blood sugar levels that are:
- Between 80 and 120 mg/dL, or 4.4 and 6.7 mmol/L, for people age 59 and younger who have no other underlying medical conditions
- Between 100 and 140 mg/dL, or 5.6 and 7.8 mmol/L, for people age 60 and older, or those who have other medical conditions, such as heart, lung or kidney disease
To help slow nerve damage:
- Follow your doctor’s recommendations for good foot care
- Keep your blood pressure under control
- Follow a healthy-eating plan
- Get plenty of physical activity
- Maintain a healthy weight
- Stop smoking
- Avoid alcohol or, if drinking is allowed, drink only in moderation
If blood sugar levels are not adequately controlled with the current treatment regimen, a different regimen may be recommended.
- For people with type 1 diabetes, this may mean taking more frequent insulin injections or using an insulin pump.
- For people with type 2 diabetes, this may mean taking an additional oral medication or starting insulin injections.
Insulin pump for Type 1 Diabetes
Insulin can be continuously administered by insulin pump, rather than through multiple daily injections with a pen injector or needle and syringe. An insulin pump may be recommended based on your preference and willingness and ability to use it.
Most pumps deliver insulin through a long spaghetti-like catheter, the end of which you insert under the skin. The catheter is taken out and re-inserted approximately every three days. You will be taught how to do this relatively painless and quick procedure. Other pumps are entirely self-contained, with a small catheter built right into the small, disposable pump unit. These pumps are replaced every five or so days.
The pump stores rapid-acting insulin in a cartridge. The pump can be taken off for up to one hour without impacting blood sugar control; if it is taken off for longer periods of time, insulin injections may be needed to control the blood sugar.
Pumps are programmed to give a small dose of insulin continuously through the day and night (basal insulin). People with an insulin pump may need to check their blood sugar levels four to seven times daily (before breakfast, mid-morning, before lunch, mid-afternoon, before the evening meal, before bedtime, and occasionally at 3 AM) while their doses are being adjusted. After doses are programmed initially, testing four times per day, including before meals, is required as you must program the pump to give pre-meal insulin based upon your blood sugar level and amount and type of food you plan to eat.
The insulin pump is sometimes used in conjunction with a continuous glucose monitoring device, which gives you more information about blood glucose levels than traditional fingersticks and a glucose meter. These devices may allow you to make better informed decisions about insulin dosing based on the blood sugar trends. Other devices automatically adjust the basal rate of insulin delivery depending on the continuous glucose monitoring results (“artificial pancreas”). These devices can improve or maintain glucose control with less risk of hypoglycemia.
The following devices, combining an insulin pump with continuous glucose monitoring, are available or will become available in the future:
- Sensor-augmented insulin pump – With this device, you use the continuous glucose monitoring readings to make adjustments in the insulin dosing. The insulin pump can be programmed to stop insulin delivery for up to two hours at a preset glucose value (“low glucose suspend” feature). This feature reduces the frequency and duration of hypoglycemia that may occur while you are sleeping.
- Partially automated insulin pump (hybrid system) – The partially automated insulin pump is a hybrid system (not fully automated) in that only the basal insulin doses are automatically adjusted depending on continuous glucose monitoring results. You need to manually request insulin doses prior to meals.
- Fully automated bihormonal insulin pump – The bihormonal system uses two commercially available pumps, with one delivering insulin and the other glucagon. The system is fully automated, in that the delivery of the insulin and glucagon is determined completely automatically by an algorithm that is, in turn, dependent on continuous glucose monitoring results. These devices have not yet been approved and are not commercially available.
The insulin pump has advantages and disadvantages; it may be helpful to talk with a person who uses a pump before deciding to try it. Most pump manufacturers have a list of people willing to speak with prospective pump users. It may also be possible to use a trial pump for a few days before committing to it.
- Advantages — Insulin pumps have the advantage of increasing flexibility in the timing of meals and other day-to-day events. This can be of great benefit for children or adults whose schedule varies from one day to the next. People who use an insulin pump do not require multiple daily injections; most patients who use the pump change their injection site every 48 to 72 hours. The other major advantage of an insulin pump is that there is less variation in the amount of insulin absorbed compared with when insulin is given with a needle and syringe. This can help reduce day-to-day variations in blood sugar levels.
- Disadvantages — The cost of an insulin pump and supplies is greater than the cost of insulin syringes and needles, although most insurance carriers cover some portion of the expenses. Some patients develop pump-associated problems, including skin infection at the injection site or pump malfunction. You must take care to monitor your blood sugar levels carefully; stopping insulin, even for a short time, can lead to a significant increase in blood sugar. Some people find the pump awkward, unpleasant, or embarrassing. However, you can disconnect the pump for brief periods, if desired.
Care for the feet
People with neuropathy do not always feel pain when there is a wound or injury on the foot. As a result, daily foot care is necessary to monitor for changes in the skin (such as cracks or wounds), which can increase the risk of infection. The American Diabetes Association recommends that people with diabetes have a comprehensive foot examination once per year, and a visual examination of the feet at each visit (usually every three to four months). Foot examinations are described in detail in a separate topic review.
Avoid activities that can injure the feet — Some activities increase the risk of foot injury and are not recommended, including walking barefoot, using a heating pad or hot water bottle on the feet, and stepping into the bathtub before testing the temperature with the hand.
Use care when trimming the nails — Trim the toe nails along the shape of the toe (rounded, not straight across) and file the nails to remove any sharp edges (figure 1). Never cut (or allow a manicurist to cut) the cuticles. Do not pop blisters, try to free ingrown toenails, or otherwise break the skin on the feet. See a healthcare provider or podiatrist for even minor procedures.
Wash and check the feet daily — Use lukewarm water and mild soap to clean the feet. Gently pat feet dry and apply a moisturizing cream or lotion.
Check the entire surface of both feet for skin breaks, blisters, swelling, or redness, including between and underneath the toes where damage may be hidden. Use a mirror or ask a family member or caregiver to help if it is difficult to see the entire foot (figure 2).
Choose socks and shoes carefully — Select cotton socks that fit loosely, and change the socks every day. Wear shoes that are fit correctly and are not tight, and break new shoes in slowly to prevent blisters (figure 3). Ask about customized shoes if your feet are misshapen or have ulcers; specialized shoes can reduce the chances of developing foot ulcers in the future. Shoe inserts may also help cushion the step and decrease pressure on the soles of the feet.
Ask for foot exams — Screening for foot complications should be a routine part of most medical visits, but is sometimes overlooked. At each visit, the shoes and socks should be removed and the clinician should visually examine the feet. Do not hesitate to ask the healthcare provider for a complete foot check at least once a year, and more frequently if there are problems.
Diabetic neuropathy medications
Neuropathic pain can be difficult to control and can seriously affect your quality of life. Neuropathic pain is often worse at night, seriously disrupting sleep.
Fortunately, only a small percentage of people with diabetic neuropathy experience pain. Pain resolves without treatment in some people over a period of weeks to months, especially if the episode of pain developed after a sudden change in health (e.g, an episode of diabetic ketoacidosis, a significant weight loss, or a significant change in blood glucose control).
There are several medications that are useful for the treatment of diabetic neuropathy and have been approved by the FDA, including duloxetine and pregabalin. Other medications are also useful, including tricyclic medications (eg, amitriptyline), gabapentin, tramadol, and alpha-lipoic acid.
- Tricyclic antidepressants — There are several tricyclic antidepressants available for the treatment of chronic pain, including amitriptyline, nortriptyline, and desipramine. Clinical trials have shown than tricyclic antidepressant drugs are effective for patients with painful diabetic neuropathy. The dose of tricyclic antidepressants used to treat diabetic neuropathy is typically much lower than that used to treat depression. These medications are usually taken at bedtime, starting with a low dose and gradually increasing over a period of several weeks. People with heart disease should not take amitriptyline or nortriptyline. Tricyclic medications can be taken with gabapentin and pregabalin, but should not be taken with duloxetine. Side effects can include dry mouth, sleepiness, dizziness, and constipation.
- Duloxetine — Duloxetine (Cymbalta) is an antidepressant that is often effective in relieving pain caused by diabetic neuropathy. In short-term clinical trials, duloxetine was more effective than placebo. However, the long-term effectiveness and safety of duloxetine for diabetic neuropathy is uncertain 3). There are no trials comparing duloxetine with other drugs for the treatment of diabetic polyneuropathy. Duloxetine is usually taken by mouth once per day on a full stomach, although in some cases it is taken twice per day. It should not be taken by people who take other antidepressant medications (see ‘Tricyclic antidepressants’ above). Side effects can include nausea, sleepiness, dizziness, decreased appetite, and constipation.
- Gabapentin — Gabapentin is an anti-seizure medication. It is usually taken by mouth three times per day. Side effects can include dizziness and confusion. Gabapentin can be taken with a tricyclic antidepressants or duloxetine. In some cases, gabapentin can be taken at night to prevent pain during sleep.
- Pregabalin — Pregabalin is an anti-seizure medication, similar to gabapentin. Pregabalin is taken by mouth, starting at bedtime at a low dose, and then gradually increasing to three times per day over a period of several weeks. Side effects can include dizziness, sleepiness, confusion, swelling in the feet and ankles, and weight gain. It may be possible to become addicted to pregabalin, and changes in dosing should be monitored carefully. Pregabalin can be taken with duloxetine or tricyclic antidepressants, but not with gabapentin.
- Anesthetic drugs — Lidocaine is an anesthetic drug that may be recommended if other treatments have not improved pain. It is applied to the painful area in a patch, which slowly releases the medication over time. Patches should stay in place for no more than 12 hours in any 24 hour period.
- Alpha-lipoic acid — Alpha-lipoic acid (ALA) is an antioxidant medication. Several short-term trials showed that it was helpful in relieving pain caused by diabetic neuropathy. Thus, alpha-lipoic acid (ALA) may be recommended to people with diabetic neuropathy who do not improve with or who cannot tolerate other treatments. However, longer-term studies are still needed to confirm its safety and effectiveness. In the United States, alpha-lipoic acid (ALA) is available without a prescription as a dietary supplement. It is usually taken by mouth once per day.
- Narcotics (opioids) — Tramadol is a pain medication that can be taken for breakthrough pain; in severe cases, it can be taken every six hours (four times per day). It can cause sedation, dizziness and confusion. It can be taken with pregabalin, duloxetine, gabapentin, and tricyclic antidepressants. It is important to note that the long-term use of narcotic medications for non-cancer pain is associated with a number of problems, including the potential for abuse, addiction, and fatal overdose, particularly for patients treated with higher dose regimens. Because of these issues, some clinicians have stopped using narcotics altogether for the treatment of painful diabetic neuropathy.
A systematic review is an analysis of the results of multiple, carefully designed studies available on a topic. In 2017 experts reviewed nearly 106 studies involving thousands of people with diabetes, examining their treatment regimens 4). Researchers found moderate evidence that the antidepressants duloxetine and venlaxine, which act as serotonin-norepinephrine reuptake inhibitors (SNRIs), were effective in reducing neuropathy-related pain 5). They also found weak evidence that botulinum toxin, the anti-seizure drugs pregabalin and oxcarbazepine, as well as drugs classified as tricyclic antidepressants (TCAs) and atypical opioids were probably effective in reducing pain. Waldfogel 6) noted that the long-term use of opioids is not recommended for chronic pain due to lack of evidence of long-term benefit and the risk of abuse, misuse and overdose. Researchers noted that while pregabalin works in the same way as gabapentin—both are often used interchangeably in clinical care—this review found gabapentin was not more effective than placebo 7). The seizure drug valproate and capsaicin cream, which were considered probably effective in the 2011 American Academy of Neurology guideline, were ineffective in this meta-analysis 8). “We hope our findings are helpful to doctors and people with diabetes who are searching for the most effective way to control pain from neuropathy,” said Waldfogel 9). “Unfortunately, there was not enough evidence available to determine if these treatments had an impact on quality of life. Future studies are needed to assess this.” There were other limitations. One was that all studies were short-term, less than six months, and all studies on effective drugs had more than 9 percent of participants drop out due to adverse effects. Longer-term outcomes should be evaluated in future studies so that side effects and continued effectiveness of the drugs can be assessed.
Managing complications and restoring function
Specific treatments exist for many of the complications of diabetic neuropathy, including:
- Urinary tract problems. Antispasmodic medications (anticholinergics), behavioral techniques such as timed urination, and devices such as pessaries — rings inserted into the vagina to prevent urine leakage — may be helpful in treating loss of bladder control. A combination of therapies may be most effective. To clear up a urinary tract infection, the doctor will probably prescribe an antibiotic. Drinking plenty of fluids will help prevent another infection. People who have incontinence should try to urinate at regular intervals—every 3 hours, for example—because they may not be able to tell when the bladder is full.
- Digestive problems. To relieve mild signs and symptoms of gastroparesis — indigestion, belching, nausea or vomiting — doctors suggest eating smaller, more-frequent meals, reducing fiber and fat in the diet, and, for many people, eating soups and pureed foods. Dietary changes and medications may help relieve diarrhea, constipation and nausea.When symptoms are severe, doctors may prescribe erythromycin to speed digestion, metoclopramide to speed digestion and help relieve nausea, or other medications to help regulate digestion or reduce stomach acid secretion.To relieve diarrhea or other bowel problems, doctors may prescribe an antibiotic such as tetracycline, or other medications as appropriate.
- Low blood pressure on standing (orthostatic hypotension). This is often helped with simple lifestyle measures, such as avoiding alcohol, drinking plenty of water, and sitting or standing slowly. Your doctor may recommend an abdominal binder, a compression support for your abdomen, and compression stockings. Some people benefit from increased salt in the diet and treatment with salt-retaining hormones. Several medications, either alone or together, may be used to treat orthostatic hypotension. Physical therapy can help when muscle weakness or loss of coordination is a problem.
- Sexual dysfunction. Sildenafil (Revatio, Viagra), tadalafil (Adcirca, Cialis) and vardenafil (Levitra) may improve sexual function in some men, but these medications aren’t effective or safe for everyone. Some are oral medications and others are injected into the penis or inserted into the urethra at the tip of the penis. Mechanical vacuum devices may increase blood flow to the penis. Another option is to surgically implant an inflatable or semirigid device in the penis. Vaginal lubricants may be useful for women when neuropathy causes vaginal dryness. To treat problems with arousal and orgasm, the doctor may refer women to a gynecologist.
Lifestyle and home remedies
These measures can help reduce your risk of diabetic neuropathy:
- Keep your blood pressure under control. People with diabetes are more likely to have high blood pressure than are people who don’t have diabetes. Having both high blood pressure and diabetes greatly increases your risk of complications because both damage your blood vessels and reduce blood flow. Try to keep your blood pressure in the range your doctor recommends, and be sure to have it checked at every office visit.
- Make healthy food choices. Eat a balanced diet that includes a variety of healthy foods — especially fruits, vegetables and whole grains — and limit portion sizes to help achieve or maintain a healthy weight.
- Be active every day. Daily activity protects your heart and improves blood flow. It also plays a major role in keeping your blood sugar and blood pressure under control. The American Diabetes Association generally recommends about 30 minutes of moderate exercise a day at least five times a week.If you have severe neuropathy and decreased sensation in your legs, your doctor may recommend that you participate in non-weight-bearing activities, such as bicycling or swimming.
- Stop smoking. If you have diabetes and use tobacco in any form, you’re more likely than are nonsmokers with diabetes to die of heart attack or stroke. And you’re more likely to develop circulation problems in your feet. If you use tobacco, talk to your doctor about finding ways to quit.
There are a number of alternative treatments that may help relieve the pain of diabetic neuropathy, such as:
- Capsaicin. When applied to the skin, capsaicin cream can reduce pain sensations in some people. Side effects may include a burning feeling and skin irritation.
- Alpha-lipoic acid. This powerful antioxidant is found in some foods and may help relieve the symptoms of peripheral neuropathy.
- Transcutaneous electrical nerve stimulation (TENS). Your doctor may prescribe this therapy, which can help prevent pain signals from reaching your brain. TENS delivers tiny electrical impulses to specific nerve pathways through small electrodes placed on your skin. Although safe and painless, TENS doesn’t work for everyone or for all types of pain.
- Acupuncture. Acupuncture may help relieve the pain of neuropathy, and generally doesn’t have any side effects. Keep in mind that you may not get immediate relief with acupuncture and will likely require more than one session.
Coping and support
Living with diabetic neuropathy can be difficult and frustrating. If you find yourself getting down, it may help to talk to a counselor or therapist.
Members of support groups can also offer you encouragement, as well as advice about living with diabetic neuropathy. Ask your doctor about support groups in your area, or for a referral to a therapist. The American Diabetes Association offers online support through its website http://diabetes.org/.
References [ + ]
|1.||↵||Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care 2006; 29:1518. http://care.diabetesjournals.org/content/29/7/1518.long|
|2, 4, 5, 6, 7, 8, 9.||↵||Pharmacotherapy for diabetic peripheral neuropathy pain and quality of life: A systematic review. Neurology Aug 2017, 89 (8) 875; DOI: 10.1212/WNL.0000000000004323 http://n.neurology.org/content/89/8/875|
|3.||↵||Duloxetine (Cymbalta) for diabetic neuropathic pain. Med Lett Drugs Ther 2005; 47:67.|