Diabetic neuropathy disease

Definition

Diabetic neuropathy (DN) is a neurological disorder caused by consequences of a primary disease—diabetes mellitus. The diabetic neuropathy may be diffuse, affecting multiple parts of the body, or focal, targeting a specific nerve or body part.

Description

Neurological damage is the result of chronically elevated blood sugar. Among all complications of diabetes, DN can be one of the most frustrating and debilitating conditions, because of the pain , discomfort, and disability it may cause, and because available treatments are limited and not always successful.

There are three main types of DN:

• Sensory neuropathy (or peripheral neuropathy , usually just referred to as neuropathy)—affects the nerves that carry sensation information to the brain, from various parts of the body, i.e.: how hot or cold something is, what the texture of something feels like, or the pain caused by a sharp object. This is the most common form of diabetic neuropathy.
• Autonomic neuropathy—affects the nerves that control involuntary activities of the body, such as the action of the stomach, intestine, bladder, and even the heart.
• Motor neuropathy—affects the nerves that carry signals from the brain to muscles, allowing all motions to occur, i.e. walking, moving the fingers, chewing. This form of neuropathy is very rare in diabetes.

The longer a person has diabetes, the more likely the development of one or more forms of neuropathy. Approximately 60–70% of patients with diabetes show signs of neuropathy, but only about five percent experience painful symptoms.

According to the categories described above, DN can lead to muscular weakness, loss of feeling or sensation, and loss of autonomic functions such as digestion, erection, bladder control, sweating, and so forth.

Demographics

In the United States, DN occurs in 10–20% of patients newly diagnosed with diabetes mellitus (DM), and its prevalence is up to 50% in elderly patients with DM. Most studies agree that the overall prevalence of symptomatic DN is approximately 30% of all patients with DM. The incidence of DN in the general population is approximately two percent.

Internationally, DN is found in 20–30% of individuals with type-2 diabetes. This number depends on the fiber type being tested and the sensitivity of the exam. Individuals with type-1 diabetes usually develop neuropathy after more than ten years of living with the disease.

It affects men and women equally, but neuropathic pain appears more frequently in females. Minority group members have more secondary complications, such as lower extremity amputations. These individuals tend to also have more hospitalizations due to neuropathic complications.

Causes and symptoms

Causes of diabetic neuropathy are likely to be different for different types of the disorder. Nerve damage is probably due to a combination of factors, such as:

• Metabolic factors: high blood glucose, long disease duration, low levels of insulin and abnormal blood fat levels
• Neurovascular factors, leading to blood vessel damage and consequent insufficient delivery of oxygen and nutrients to the nerves
• Autoimmune factors, causing nerve inflammation
• Mechanical nerve injury, such as carpal tunnel syndrome
• Inherited traits that increase susceptibility to nerve disease
• Lifestyle factors, such as smoking or alcohol use

Symptoms depend on the neuropathy type and affected nerves. Some people show no symptoms at all. Often, symptoms are minor at first, and because most nerve damage occurs over several years, mild cases may go unnoticed for a long time. Symptoms may include:

• Numbness, tingling, or pain in the toes, feet, legs, hands, arms, and fingers
• Wasting of feet or hands muscles
• Indigestion, nausea, or vomiting
• Diarrhea or constipation
• Dizziness or faintness due to a drop in postural blood pressure
• Problems with urination
• Erectile dysfunction (impotence) or vaginal dryness
• Weakness

In addition, weight loss and depression are not a direct consequence of the neuropathy but, nevertheless, often accompany it.

Diagnosis

Diabetic neuropathy is diagnosed on the basis of a clinical evaluation, analyzing the patient's history, symptoms and the physical exam. During the exam, the doctor may check blood pressure and heart rate, muscle strength, reflexes, and sensitivity to position, vibration, temperature, or a light touch.

The physician may also do other tests to help determine the type and extent of nerve damage:

• A comprehensive foot exam assesses skin, circulation, and sensation. Other tests include checking reflexes and assessing vibration perception.
• Nerve conduction studies check the transmission of an electrical current through a nerve. This test allows the doctor to assess the condition of all the nerves in the arms and legs.
• Electromyography (EMG) shows how well muscles respond to electrical signals transmitted by nearby nerves. This test is often done at the same time as nerve conduction studies.
• Quantitative sensory testing (QST) uses the response to stimuli, such as pressure, vibration, and temperature, to check for overt neuropathy. QST is increasingly used to recognize sensation loss and excessive irritability of nerves
• Heart rate variability shows how the heart responds to deep breathing and to changes in blood pressure and posture.
• Nerve or skin biopsies are used in research settings

Treatment team

Proper management of diabetic patients requires a skilled team including collaborating specialists. Depending on the qualifications of the patient's primary physician, other professionals are recruited as needed, such as an ophthalmologist, podiatrist, cardiologist, nutritionist, nurse educator, neurologist , vascular surgeon, endocrinologist, gastroenterologist and urologist. A nurse educator can ease the interface between otherwise independent specialists. Without such a team mentality, the diabetic patient is often set adrift, forced to cope with conflicting instructions and unneeded repetition of tests.

Treatment

The first step is to bring blood glucose levels down to the normal range to prevent further nerve damage. Blood glucose monitoring, meal planning, exercise , and oral drugs or insulin injections are needed to control blood glucose levels. Although, symptoms may get temporarily worse when blood sugar is first brought under control, over time, maintaining normal glucose levels helps lessen neuropathic symptoms. Importantly, good blood glucose control may also help prevent or delay the onset of further complications.

Additional treatments depend on the type of nerve problem in consideration, and are include:

• Foot care—Clean the feet daily, using warm water and a mild soap. Inspect the feet and toes every day for cuts, blisters, redness, swelling, calluses, or other problems. Always wear shoes or slippers to protect feet from injuries, and prevent skin irritation by wearing thick, soft, seamless socks. Schedule regular visits with a podiatrist.
• Pain relief—To relieve pain, burning, tingling, or numbness, the physician may suggest aspirin, acetaminophen, or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. People with renal disease should use NSAIDs only under a doctor's supervision. A topical cream called capsaicin is another option. Tricyclic anti-depressant medications such as amitriptyline, imipramine, and nortriptyline, or anticonvulsant medications such as carbamazepine or gabapentin may relieve pain in some people. Codeine may be prescribed for a short time to relieve severe pain. Also, mexiletine, used to regulate heartbeat, has been effective in reducing pain in several clinical trials .
• Gastrointestinal problems—To relieve mild symptoms of stomach discomfort, doctors suggest eating small, frequent meals, avoiding fats, and eating less fiber. When symptoms are severe, the physician may prescribe erythromycin to speed digestion, metoclopramide for the same reason and to help relieve nausea, or other drugs to help regulate digestion or reduce stomach acid secretion.
• Urinary and sexual problems—To treat urinary tract infections, physicians can prescribe antibiotics and suggest drinking plenty of fluids. Several methods are available to treat erectile dysfunction caused by neuropathy, including taking oral drugs, using a mechanical vacuum device, or injecting a vasodilating drug into the penis before intercourse. In women, vaginal lubricants may be useful when neuropathy causes vaginal dryness.

Recovery and rehabilitation

Physical therapy may be a useful adjunct to other therapies, especially when muscular pain and weakness are a manifestation of the patient's neuropathy. The physical therapist can instruct the patient in a general exercise program to maintain his/her mobility and strength.

Occupational therapy may be necessary in cases where a person loses a limb due to secondary complications and needs functional training to regain his/her independence.

Clinical trials

There are numerous open clinical trials for diabetic neuropathy disease:

• Gene Therapy to Improve Wound Healing in Patients With Diabetes, at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Long-Term Treatment and Re-Treatment of Lower Extremity Diabetic Ulcers with Regranex or Placebo, sponsored by Johnson & Johnson Pharmaceutical Research and Development RhVEGF (Telbermin) for Induction of Healing of Chronic, Diabetic Foot Ulcers, sponsored by Genentech
• Study of Three Fixed Doses of EAA-090 in Adult Outpatients with Neuropathic Pain Associated with Diabetic Neuropathy, sponsored by Wyeth-Ayerst Research
• Treatment for Symptomatic Peripheral Neuropathy in Patients with Diabetes, LY333531 Treatment for Symptomatic Peripheral Neuropathy in Patients with Diabetes and Treatment of Peripheral Neuropathy in Patients with Diabetes, sponsored by Eli Lilly and Company
• VEGF for Diabetic Neuropathy, at the Caritas St. Elizabeth's Medical Center of Boston.

For updated information on clinical trials, visit the website www.clinicaltrials.org, sponsored by the United States government.

Prognosis

The mechanisms of diabetic neuropathy are poorly understood. At present, treatment alleviates pain and can control some associated symptoms, but the process is generally progressive.

Complications of diabetic neuropathy may include:

• Progression to cardiovascular autonomic neuropathy, a relatively rare occurrence which can eventually cause death
• Peripheral neuropathy that leads to foot ulcers and leg amputations
• Injuries associated with automonic neuropathy, including those from dizziness and falling
• gastric distress leading to nausea and vomiting, diarrhea and dehydration, which could impair the ability to regulate blood sugar.

Special concerns

Prevention of diabetic neuropathy can be achieved by establishing good control over blood sugar levels at the onset of diabetes. Even when symptoms of neuropathy are already present, maintaining normal blood sugar levels reduces pain significantly. Drugs such as some over-thecounter anti-inflamatories may aid in prevention, as well as deterrence, of neuropathy by keeping inflammation to a minimum.

Resources

BOOKS

Parker, James N., Phillip M. Parker. The Official Patient's Sourcebook on Diabetic Neuropathy: A Revised and Updated Directory for the Internet Age. Icon Group, International, 2002.

U.S. Dept of Health and Human Services. Diabetic Neuropathies: The Nerve Damage of Diabetes. NIDDK, National Diabetes Information Clearinghouse, 2002.

PERIODICALS

Podwall D., and C. Gooch. "Diabetic neuropathy: clinical features, etiology, and therapy." Curr Neurol Neurosci Rep 4. (January 2004): 55–61.

Hughes, R. A. C. "Peripheral neuropathy." BMJ 324 (February 2002): 466–469.

Vinik, A. I., R. Maser, B. Mitchell, and R. Freeman. "Diabetic Autonomic Neuropathy." Diabetes Care 26 (2003): 1553–1579.

OTHER

Diabetic Neuropathies: The Nerve Damage of Diabetes. National Institute of Diabetes and Digestive and Kidney Diseases. (January 4, 2004). <http://diabetes.niddk.nih.gov/>.

ORGANIZATIONS

American Diabetes Association (National Service Center). 1701 North Beauregard Street, Alexandria, VA 22311. (703) 549-6995 or (800) 232-3472 or (800) DIA-BETES. customerservice@diabetes.org. <http://www.diabetes.org>.

Centers for Disease Control and Prevention (National Center for Chronic Disease, Prevention and Health Promotion, Division of Diabetes Translation). Mail Stop K-10, 4770 Buford Highway, NE., Atlanta, GA 30341-3717. (301) 562-1050 or (800) CDC-DIAB (800-232-3422). diabetes@cdc.gov. <http://www.cdc.gov/diabetes>.

Juvenile Diabetes Research Foundation International. 120 Wall Street, 19th floor, New York, NY 10005. (212) 785-9500 or (800) 533-2873; Fax: (212) 785-9595. info@jdrf.org. <http://www.jdrf.org>.

National Diabetes Education Program. 1 Diabetes Way, Bethesda, MD 20892-3600. (800) 438-5383. <http://ndep.nih.gov>.

National Institute of Neurological Disorders and Stroke. P.O. Box 5801, Bethesda, MD 20824. (800) 352-9424. <http://www.ninds.nih.gov>.

Greiciane Gaburro Paneto

Francisco de Paula Careta

Iuri Drumond Louro