Neuropathy


 

One of the major diabetes complications everyone hears about is neuropathy. When people think of neuropathy they think of losing feeling in their feet. They are often surprised that chronically high blood glucose can damage nerves throughout the body including those that not only go down to the legs, but also the arms and different organs including intestines, bladder, and penis among others. Keeping blood glucose as close to the target range as possible and maintaining a healthy lifestyle (e.g., not smoking, eating a healthy diet, getting regular physical activity, etc.) is the best way to prevent neuropathy.1

Statistics

  • About 50% of people with diabetes will eventually develop peripheral neuropathy2,8
  • At least 30% of people with T1D have cardiovascular autonomic neuropathy after 20 years and up to 60% of people with T2D have it after 15 years1
  • It is estimated that about 5.2% of people with Type 1 diabetes and 1% of people with Type 2 diabetes have gastroparesis 12
  • Between 43% to 87% of people with Type 1 diabetes and 25% of people with Type 2 have bladder dysfunction3
  • Over 52% of men with diabetes have erectile dysfunction: 37.5% of men with T1D, 66.3% of men with T2D9
  • 1 in every 3 people with diabetes have an entrapment neuropathy26

Neuropathy results in damage to the nerves outside the brain and spinal cord. The brain and spinal cord make up the central nervous system. The nerves that branch out from the spinal cord and go to all other parts of the body are called the peripheral nervous system. When nerves, which take signals to and from the brain and spinal cord to and from the rest of the body, are damaged it is called neuropathy.

Nerves are a complex network of cells that send and receive signals to and from the muscles, skin, and major organs. When neuropathy occurs, the relay system between the brain and spinal cord and the rest of body is damaged. Communication between the individual nerve cells (called neurons) is disrupted.

The two most common types of neuropathy people with diabetes develop are called peripheral and autonomic neuropathy. Peripheral neuropathy refers to damage to the nerves that control movement and sensation. Autonomic neuropathy affects the nerves that go to the major internal organs like the heart, bladder, and intestines. Since peripheral neuropathies and cardiovascular autonomic neuropathy (a type of autonomic neuropathy) are most common, there is significantly more research on them compared to other neuropathies (atypical forms such as mononeuropathy and radiculopathy).1,3

Peripheral Neuropathy

Peripheral neuropathy can include any disorder of the peripheral nervous system but is most commonly seen in the hands and feet. Unfortunately, it is the cause of 80% of amputations after foot injury or wound. It begins in the furthest parts from the center of the body (e.g., fingers, toes) and then progresses toward the body. It is one of the most common and expensive complications of diabetes. It is associated with chronic high blood glucose and cardiovascular risk factors. It appears that the tiny blood vessels are damaged and changes in the nerves occur similar to diabetic retinopathy and nephropathy. Intensively managing blood glucose has been shown to stop progression and/or improve symptoms of neuropathy.

Initially symptoms can include pain, burning (shooting pain), and tingling. Pain is often worse at night in the feet and anything touching the area affected by neuropathy is especially painful (e.g., socks or sheets when they touch the feet). People also lose the sensation of hot/cold or touch and can experience weakness and a numbing sensation. People with peripheral neuropathy experience an increase in falling and injuries because their balance is affected by the lack of feeling and muscle weakness. In addition, they may not notice if they have a cut or sore on their foot/legs because they do not feel it, which can progress into a more serious issue if not treated early.1

John McAuliffe, who was diagnosed with Type 2 diabetes almost 20 years ago shares, “Neuropathy sucks — I was diagnosed with Type 2 because I had a sore on my foot (so I already neuropathy when I was diagnosed). I am not steady on my feet and can’t feel anything below my knees. As I am getting older, I am weaker on my feet and can’t stand long. I did what the doctors told me but often my A1c would be high and then they would add another medication. It wasn’t until I got a cut on my foot that almost took my foot and life that I got a wake-up call. I have lost 60 pounds and my A1c has been in the 6s ever since. Take care of yourself is my advice.”

Diagnosis

It is recommended that people with diabetes keep their blood glucose as close to the target range as possible to avoid and/or delay developing and/or stop the progression of neuropathy. It is also recommended for diabetes care providers to screen for diabetic neuropathy at Type 2 diabetes diagnosis, after 5 years of Type 1 diabetes diagnosis and then annually for both thereafter. Initially screening is conducted via questions by the doctor and then with a monofilament and/or tuning fork and sometimes pin prick. Ankle reflexes and temperature sensation may also be evaluated. Additional tests may be conducted to assess the neuropathy including blood tests to rule out other causes of the symptoms and nerve conduction studies.1,3

Treatment

Treatment includes intensively managing diabetes, weight loss if overweight or obese, eating healthy, getting regular physical activity, drinking alcohol in moderation, and stopping smoking. In addition, for painful neuropathy, medications will be prescribed. Depending on symptoms and their impact on quality of life (e.g., disrupting sleep, interrupting daily activities) and having mental health conditions (such as anxiety or depression) will also be addressed. People are usually asked to monitor their symptoms to assess treatment effectiveness. It is also recommended to visually inspect the skin of the area that is affected by neuropathy to make sure there are no wounds.1,3,10

Autonomic Neuropathy

Autonomic neuropathy affects the nerves that go to the major internal organs like the heart, bladder, and intestines. Since these are vital organs, there are many nerves that go to them, making the symptoms and signs of neuropathy different depending on the organ system affect. The neuropathies below are clustered by organ system.

Cardiovascular Autonomic Neuropathy

Cardiovascular autonomic neuropathy (CAN) is the most studied of all the autonomic neuropathies as they affect the heart. It is significantly more common the longer a person has diabetes. CAN is an independent risk factor for reduced blood flow through the coronary arteries, heart attack, and cardiovascular deaths. CAN is also associated with the progression of diabetic nephropathy. Chronic high blood glucose is one of the factors in developing CAN. There are several cardiovascular issues that can develop including issues in regulating blood pressure.1,3 Please refer to Atherosclerotic Cardiovascular Disease (ASCVD) section for cardiovascular complications including high blood pressure, high cholesterol, ASCVD, heart attack, and heart failure.

There are often no signs of early cardiovascular autonomic neuropathy. It is often only seen in an electrocardiogram (ECG or EKG that measures the heart’s electrical activity) with decreased heart rate variability. Once the CAN progresses, a fast heart beat while resting (greater than 100 beats per min), known as resting tachycardia, and orthostatic hypotension (a drop in blood pressure when standing) develop.1,3

Symptoms of orthostatic hypotension can include light-headedness, weakness, visual impairment, and/or briefly fainting when standing. Individuals with CAN may have issues with exercise. A diagnosis is made after taking a full health history (including glucose management), ruling out other health conditions and medication that could cause the symptoms, and potentially conducting additional cardiac tests if needed.1,3

Treatment is focused on alleviating symptoms of CAN through medications. In addition, keeping blood glucose as close to the target range as possible, medications to treat other cardiovascular risk factors of high blood pressure and cholesterol, and lifestyle modifications (e.g. eating healthy, getting regular physical activity, drinking the recommended amount of fluids, losing weight, stopping smoking, reduce alcohol intake, getting enough sleep at night, and managing stress) are recommended.1,3

Gastrointestinal Neuropathy

Gastrointestinal (GI) neuropathies affect the rate at which food is digested and absorbed. This can directly affect the management of blood glucose. Esophageal dysfunction (issue affecting the esophagus or food pipe) can cause spitting up of food (regurgitation) and difficulty and/or discomfort in swallowing. In addition, people develop diabetic diarrhea, which is characterized by diarrhea with alternating constipation and/or inability to hold your bowels. Colonic hypomotility, known as constipation, can also develop. This constipation can also alternate with diarrhea.1,11

Among the GI neuropathies, gastroparesis is the most widely studied. Read more about gastroparesis, here.

Bladder Dysfunction

Bladder dysfunction, a urogenital neuropathy, is also known as diabetic cystopathy. Just like in other organs, the nerves that control the bladder can be affected. Urine is made by the kidneys and travels through two tubes (ureters) into the bladder. The bladder is like a balloon and stores the urine. When the bladder is full, the nerves send signals to the brain saying it needs to be emptied. During urination, the bladder muscles squeeze and two valves (sphincters) open to allow urine to flow out of the body through the urethra (a tube).

In this condition, bladder dysfunction appears to be a progressive condition with the sensation to urinate gradually lost, the bladder having a greater volume capacity, and issues in emptying the bladder. The causes for this seem to be a combination of factors from high blood sugar affecting the nerves, muscles, and tissues.4,5,7

Diagnosis

Diagnosis includes a physical exam as well as urodynamic evaluation. A urodynamic evaluation measures how well the bladder, sphincters, and urethra are storing and releasing urine. This can also indicate if there are any leakages from the bladder. This evaluation consists of several different tests including ones that measure speed and volume of urine, the amount of urine left in the bladder after urination, how much the bladder can hold, when the sensation to urinate occurs, nerve conduction, and imagining and videos of how the bladder functions.6,7

Treatment

Treatment depends on the person’s symptoms and the effect of these symptoms have on a person’s daily life, and on the urodynamic test results. This may include medications, surgeries, and lifestyle modifications. Behavioral changes include keeping glucose as close to target range as possible, stopping smoking, losing weight if overweight or obese, changes in fluid intake, and bladder training (emptying bladder every 2-4 hours).1,7,8

Sexual Complications

Both females and males can experience sexual dysfunction due to neuropathy. In addition to affecting the physical ability to have and/or enjoy sex, libido can be affected.3

Erectile Dysfunction

Neuropathy is the leading cause of impotence, also known as erectile dysfunction (ED), in men (the person can no longer have or keep an erection firm enough to have sex). Erectile dysfunction occurs 3.5 times more in men with diabetes than in men without diabetes. High blood glucose can cause damage to the tiny blood vessels and nerves that control sexual response and also reduce blood flow to the penis. Additionally, some medications, as well as medical conditions and surgeries, can also contribute to ED.1,3,9

Diagnosis is made by medical history (including medications as they may contribute to ED), physical exam, and ruling out other hormonal conditions. Often questions are used. Treatment includes oral medication and relationship/sexual counseling. If oral medication does not work, intraurethral medication (suppository inserted directly into the head of the penis) or medication injected into the penis can be used. Managing blood glucose intensively (which may improve symptoms) as well as lifestyle modifications are recommended (e.g., reducing alcohol intake, regular physical activity, eating healthy, stopping smoking, managing stress, etc.). In addition, managing blood pressure, cholesterol levels, and addressing mental health/emotional issues such as anxiety and depression is key to successful treatment.14,15,16

Retrograde Ejaculation

Retrograde ejaculation is a fairly rare type of ejaculation problem. It occurs when a man ejaculates and the semen enters the bladder instead of coming out (through the urethra) of the penis. This can occur for several reasons, but in people with diabetes it occurs (in the absence of other health issues) because of neuropathy (nerve damage) to the nerves in your bladder due to hyperglycemia. This can cause infertility. In addition, little or no semen comes out when you ejaculate. You may have cloudy urine when you urinate after orgasm. To diagnose retrograde ejaculation, a health history and physical exam will be conducted and urine will be collected after ejaculation. Treatment includes medications to treat other neuropathies. Fertility counseling may be needed if infertility is an issue for the couple. Treatment recommendations may also include relationship/sexual counseling.3,15,16

Female Sexual Dysfunction

Although male issues in having sex are more often discussed, there are many issues women may develop as a consequence of hyperglycemia. These include pain during intercourse, inadequate lubrication, and decreased sexual arousal. Female sexual dysfunction is more common in women with diabetes than those without diabetes.1,3

Damage to the blood vessels and nerves that supply the vagina and clitoris can cause issues with vaginal dryness and arousal. The nerve damage reduces sensitivity just like in other areas of the body. Issues with hormone levels should also be evaluated as diabetes can affect hormones.1,3,16

After an evaluation, lubricants may be recommended to treat vaginal dryness. Managing blood glucose intensively as well as making lifestyle modifications are recommended (reducing alcohol intake, regular physical activity, eating healthy, stopping smoking, managing stress, etc.), managing blood pressure and cholesterol levels, and addressing mental health/emotional issues such as anxiety and depression. Treatment recommendations may also include relationship/sexual counseling.6

Sweat Glands

Keeping your body at a constant temperature is a complex regulatory function of the body. It can be affected by hormonal issues, cardiovascular issues, stress, and neuropathy. Sudomotor refers to anything that stimulates sweat glands. Sudomotor dysfunction, a type of autonomic neuropathy, may develop as dry skin, anhidrosis (lack of sweat to normally cool the body), or heat intolerance. There is also a rare type of sudomotor dysfunction, called gustatory sweating, that causes excessive sweating in the head and neck that is triggered by eating.1,3

Diagnosis will include a health history and physical exam. In addition, a quantitative sudomotor axon reflex test (QSART) may be ordered, which evaluates how the nerves that regulate your sweat glands respond to stimulation. A thermoregulatory sweat test may also be conducted. This is a test in which the person is covered in a powder that changes color. The person lays in a chamber where the temperature is gradually increased and pictures are taken of the powder (and how it changed color) as the person begins to sweat.3 Treatment includes moisturizing dry skin, antiperspirant, and medications.

Hypoglycemia Unawareness

Hypoglycemia unawareness occurs when a person does not have any symptoms of being low (e.g., shakiness, palpitations, sweating, etc.) when blood glucose falls in the low range (below 7 mg/dL/3.9mmol/L). The person is unaware of their glucose dropping which can be dangerous, particularly at night, so this issue should be discussed with the diabetes healthcare provider as soon as possible. People with hypoglycemia unawareness are at high risk for severe hypoglycemia because they don’t feel the earlier warning signs of being low so they, therefore, don’t treat it. This can lead to unconsciousness, seizures, and death.

Up to 40% of people with Type 1 diabetes have hypoglycemia unawareness. People who have had diabetes for a longer duration and those that have frequent hypoglycemia seem to be more at risk for developing this condition. It is also thought that autonomic neuropathy can contribute to developing this condition, so it is recommended that diabetes healthcare providers screen people with cardiovascular autonomic neuropathy (CAN) for hypoglycemia unawareness.1,25

Often people become fearful of going low, missing it (since they don’t have symptoms), and then having a severe hypoglycemic episode, which is called fear of hypoglycemia (FOH). People with FOH often run their blood glucose higher to avoid hypoglycemia, driving their HbA1c higher (putting them at risk for developing complications). Hypoglycemia unawareness and FOH can negatively impact a person’s quality of life. People also tend to have more anxiety, diabetes distress, and depression so treatment is important.1,25,28

Working with the diabetes treatment team to establish and refine a treatment regimen is key to keeping blood glucose in the individual’s target range and avoid hypoglycemia. Diabetes education and the use of a CGM can be helpful so that the CGM alarm alerts the person to a low and/or dropping blood glucose level. Newer insulins and insulin pumps, as well as automated insulin delivery devices (e.g., predictive low-glucose devices stop insulin delivery if CGM is indicating a drop in blood glucose or hybrid closed loop devices use CGM readings to adjust basal insulin up or down), can also be helpful in managing blood glucose. Treatment to re-establish sensation of hypoglycemia is recommended, such as Blood Glucose Awareness Training, as well as addressing anxiety, FOH, and other psychosocial issues the person is experiencing.1,25,29

Diabetic Radiculoplexus Neuropathy

Diabetic radiculoplexus neuropathy, an atypical neuropathy, is also known as diabetic amyotrophy or diabetic polyradiculoneuropathy. This usually affects men with Type 2 diabetes. It affects the nerves in the thighs, legs, hips, and buttocks. It can affect only one side of the body or both.

The most common symptoms include intense thigh pain, stomach pain, weight loss, and then weakness in your thighs making it hard to stand up. People may also develop foot drop (difficulty in lifting the front part of the foot while walking so it may drag – please refer to the “Foot Complications” section for additional information). Diagnosis is made after a health history, physical exam, blood tests, and an electrophysiological assessment (which evaluates how well nerves are working), and sometimes scans.

Diabetes amyotrophy often gets better over time by itself. Medications for pain (including those that target nerve pain) are prescribed as well as keeping tight management of blood glucose, eating healthy, exercising, and taking other medications as recommended. Physical therapy is often recommended to maintain and improve your muscles as well as to recommend assistive devices (e.g., a high toilet seat).

Mononeuropathy

Mononeuropathy, an atypical neuropathy, is diagnosed when there is nerve damage to a single nerve outside the brain and spinal cord. These types of neuropathies are more common in people with diabetes than those without. They can affect sensation (feeling in the affected area). The more commonly affected nerves include the femoral, sural, sciatic, and ulnar. Symptoms include pain numbness, tingling, weakness, and sometimes loss of motion. Diagnosis includes health history, physical exam, and often scans and tests to assess the nerves. These mononeuropathies typically have a sudden onset and usually resolve on their own within a period of 6 weeks. Treatment is typically focused on managing symptoms.1,17,27,28

Cranial neuropathy is a mononeuropathy that affects the nerves in one of the twelve cranial nerves that connect with the brain directly. The most commonly affected are the nerves that affect your vision. This can cause double vision and drooping eyelids. Symptoms include pain around the eye and forehead and then issues in vision (e.g., double vision). Diagnosis includes an eye exam, blood tests, and possibly scans. Treatment includes keeping blood glucose as close to the target range as possible, pain management, and the use of an eye patch or glasses to reduce double vision. This condition usually resolves by itself, but some people are left with eye weakness or drooping eyelid.17,27,28

Entrapment (also called compression) syndromes are different because they begin slowly and progressively get worse due to excessive pressure on the nerve. They usually need intervention to reduce and/or resolve symptoms since they do not resolve by themselves. The most common entrapment syndrome is carpel tunnel. Symptoms include pain, numbness, tingling, and weakness in the hands, wrist, and fingers. Diagnosis includes health history, exam, and often electrophysiological tests. Treatment can include wearing a splint and assistive devices, medications, and often surgery to release the pressure on the nerve.1,17,27,28

Treatment Induced Neuropathy (Insulin Neuritis)

Treatment-induced neuropathy, historically called insulin neuritis, is a condition people experience after a period of rapid intensive blood glucose management after high blood glucose for a long period of time. This can occur in people with both Type 1 and Type 2 diabetes who are intensively treated with insulin and/or oral hypoglycemic medication(s).18,19,20

Symptoms can include painful peripheral neuropathy and/or symptoms of autonomic neuropathy. In addition, weight loss and mood issues have also been reported. The goal of treatment is to manage pain and other symptoms, which will gradually improve with time. This condition resolves by itself but the management of symptoms, while the person is experiencing them, is key.18,19,20

Psychosocial Aspects of Neuropathy

Neuropathy is one of the most painful complications from diabetes so it is not surprising that there are many psychosocial issues associated with having the complication. In addition to pain, there can be changes in daily activities (e.g., limited mobility), which also impact the quality of life.21,22 Pain has also been associated with anxiety in people with peripheral neuropathy.23 Almost 70% of people with peripheral neuropathy report issues with sleeping, work productivity, anxiety, and depression.9 People with autonomic neuropathies also report a poor quality of life.10,11 So, it is not surprising that a standard part of neuropathy treatment is the assessment of the psychosocial functioning of a person experiencing these symptoms, especially depression. Research has found that it is important to address these social and emotional/psychological issues a person is having to improve treatment adherence for neuropathy, response to treatment of the neuropathy, and their quality of life.1,10,11

The American Diabetes Association (ADA) has recommended in the Standard of Medical Care in Diabetes that clinicians should assess for depression, anxiety, diabetes distress, as well as other psychosocial issues when a complication develops or progresses, when a new treatment is started and then at periodic intervals. Dealing with diabetes is overwhelming enough, but adding pain and possible impairment to a person’s normal functioning is devastating. You may want to get some extra support to help you cope. It is important to talk to your diabetes health care provider about how you are feeling and your worries. They can recommend some practical tips for adjusting to your new norm and also refer you to a mental health provider that has experience in helping patients cope with diabetes complications. Taking care of yourself both medically and psychologically can help improve your overall quality of life and long-term health.

 


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WRITTEN BY Alicia McAuliffe-Fogarty, PhD, CPsychol, POSTED 12/13/20, UPDATED 12/18/20

Dr. Alicia McAuliffe-Fogarty was diagnosed with Type 1 diabetes in 1987. She is a Clinical Health Psychologist specializing in diabetes, completing her fellowships at the Yale University School of Medicine. Dr. McAuliffe-Fogarty founded the Circle of Life Camp for children with diabetes, was Vice President of the Lifestyle Management Team at the American Diabetes Association and Vice President of Patient-Centered Research at the T1D Exchange. She is a clinical and scientific consultant to nonprofit and biotech/pharmaceutical companies leading research, strategy, content creation and program development.