Introduction to Peripheral Neuropathy

Diabetic Peripheral Neuropathy

Diabetes mellitus (type 1 and type 2) is the most common cause of peripheral neuropathy in Western countries and accounts for more diabetes-related hospitalizations than any other complication. The cause of diabetic neuropathy is not completely understood but some researchers theorize that the metabolic consequences of insulin deficiency and hyperglycemia (higher than normal levels of sugar in the blood) are related to the initial damage to the nerve fibers and vascular insufficiency, which is common in diabetes, and which may accelerate the neuropathic injury. Additional factors related to the development of diabetic peripheral neuropathy include duration of diabetes and obesity.

It appears that hypertension, age, smoking, and dyslipidemia may also elevate the risk of developing diabetic peripheral neuropathy.

Peripheral neuropathy is one of the most common long-term complications of diabetes. Estimates of incidence vary widely and range from approximately 10% to 90% with the average reported as approximately 60%. It occurs equally among type 1 and type 2 diabetes and has more of an effect on the quality of life of diabetic patients than other aspects of the condition, such as dietary restriction. The number of people affected by diabetic neuropathy increases with age (approximately 50% of diabetics over the age of 60) since it can develop several years after the onset of diabetes. It is important to distinguish the origin of the symptoms of peripheral neuropathy in the diabetic patient since up to 10% of diabetics may have signs of peripheral neuropathy from nondiabetic causes. It is not clear whether progression of diabetic neuropathy is closely related to controlling the level of glucose in the blood (glycemic control).

The most serious complication associated with diabetic neuropathy is foot ulceration which is due to:

  • Loss of sensation in the feet (patient may not be aware of injury or pressure sores so it goes untreated)
  • Abnormalities of motor function
  • Autonomic involvement that causes dry, chapped skin because of reduced production of sweat
  • Poor circulation to the extremities

Diabetic foot ulcers can lead to the onset of gangrene and may require amputation. The presence of neuropathy significantly increases the risk of amputation. By some estimates, diabetic neuropathy is responsible for up to 75% of non-trauma related amputations among diabetics. This highlights the need for diabetic patients to be screened for any signs of neuropathy even if there is no clinical evidence of neuropathy since early symptoms may be subacute or mild.

The progression of diabetic neuropathy differs for type 1 and type 2 diabetes. In type 1 diabetes, there is typically a rapid deterioration of nerve function soon after onset and then it slows, whereas, in type 2 diabetes, the nerve damage and symptoms of neuropathy are present at diagnosis and progress thereafter at a steady rate.

Diabetic neuropathy is typically a sensory neuropathy but often affects the autonomic nervous system as well. Nearly 50% of diabetic patients with neuropathy may have symptoms of autonomic peripheral neuropathy which can be mild or subclinical but, nevertheless, potentially life threatening. Symptoms associated with cardiac disease, (e.g., silent cardiac ischemia, orthostatic hypotension) can be fatal or can cause significant morbidity. Cardiac disease accounts for up to 25% of deaths of diabetic patients over a 10-year period from the time of diagnosis and is an independent risk factor for stroke. Medical professionals involved in the care and treatment of diabetic neuropathy include an endocrinologist, neurologist, rehabilitation specialist, and physical and/or occupational therapist. Other professionals who may be involved include a social worker or vocational counselor.

Common forms of diabetic neuropathy include:

  • Focal neuropathy - This condition occurs in older adults with diabetes and is usually characterized by intense acute pain which usually resolves within 6-8 weeks. This category includes mononeuropathy, radiculopathy, and entrapment syndromes (e.g. carpal tunnel syndrome) which occur approximately three times as often in the diabetic population.
  • Distal symmetric polyneuropathy - This is the most commonly recognized form of diabetic neuropathy that affects the longer axons to the lower limbs. It often appears with the beginning of insulin therapy for diabetes or with stress. It may manifest as sensory and/or sensorimotor neuropathy.

Distal symmetric polyneuropathy can be further subdivided into the types of nerve fibers affected, namely small fibers or large fibers.

Small Fiber Neuropathy

Small fiber pain is not well understood. Small nerve fiber dysfunction often occurs quite early in diabetes with symptoms of pain of varying degrees of intensity and severity as well as exaggerated reactivity to touch (hyperalgesia). It is thought that hyperglycemia may play a role in the increased sensitivity to pain caused by damage to these fibers. Diabetic neuropathy seems to progress as these fibers (c-fibers) are damaged. As it progresses, there is a loss of sensory-related symptoms such as decreased sensitivity to:

  • Heat
  • Pinprick
  • Temperature recognition of warm and cold stimuli

When the situation becomes chronic, there is no longer need for a stimulus to cause the pain and it is always present. Eventually, the fibers may die at which time the patient may no longer experience pain and may experience numbness.

Large Fiber Neuropathy

Large nerve fibers are myelinated and injury to these nerve fibers results in varying degrees of severity of symptoms such as:

  • Impaired sense of vibration
  • Impaired sense of pressure or touch
  • Loss of 2-point discrimination - the ability to distinguish between being touched at 1 or 2 points close to each other with a sharp object such as a pin
  • Dull pain in the bones of the lower leg or foot
  • 'Hot foot' due to increased blood flow
  • Shortened Achilles tendon

Motor involvement is usually less severe than sensory involvement and is usually restricted to lower limbs. Symptoms include:

  • Muscle atrophy
  • Weakness in the toes and feet
  • Reduced or absent ankle reflexes

Most cases of diabetic neuropathy are a mixture of large and small fiber damage. Many patients experience the "stocking-glove" distribution of pain in the legs as an early sign of sensory loss. While symptoms from large fiber involvement (e.g., weakness, poor coordination) affect daily activities and may make a person more prone to falling, the effects of small fiber damage are more debilitating and significantly affect the overall wellbeing of the person since the pain may be very intense, frequent, and/or last a long time.

Pain in diabetic peripheral neuropathy can range from mild to excruciating. It is typically localized in the feet, is worse at night, and may improve while walking. Pain may consist of a deep ache and/or may also have a burning or stabbing-like (lancinating) quality. Although some pain in diabetic neuropathy may resolve on its own, if the pain persists for more than 3-6 months, it is less likely to disappear and is considered chronic. Resolution or remission of pain appears to be related to:

  • Short duration of diabetes
  • Change of metabolic status (e.g. glucose control)
  • Preceding weight loss
  • Sensory loss that is not severe

To read more about diabetic peripheral neuropathy, please click on the following link: http://www.medifocus.com/abstracts.php?gid=NR021&ID=18227494