Diabetic Neuropathy: The Latest Facts

Damage to the nerves is a common complication of diabetes, known as “diabetic neuropathy” or “neuritis. It is often diagnosed late because the onset is silent or even without apparent signs. The most feared symptom is the onset of chronic nerve pain.

Diabetes

Diabetes

High blood sugar, or “hyperglycemia,” affects nerve function which can lead to neuropathy.

This neuropathy can affect either the “peripheral nerves” or the nerves of the “autonomic nervous system”.

Damage to the peripheral nerves may be limited to one nerve (“mononeuropathy” or “mononeuritis”) or may affect all the nerves in one limb or the body (“polyneuritis” or “polyneuropathy”).

What is diabetic neuropathy?

During diabetes, high blood sugar, or “hyperglycemia,” affects several tissues in the body, especially the nerves. This high blood sugar can have a direct effect on the nerves (nerve fibers) or the walls of the small vessels that supply them with blood (“microangiopathy”). The damage can range from functional impairment (slowing down of electrical conduction) to damage to the nerve structure itself, which in this case is difficult to reverse.

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Diabetes can affect all the nerves in the body. It affects two types of nerves: “peripheral nerves” and “nerves of the autonomic nervous system”. Peripheral nerves control the voluntary movement of muscles and allow us to feel pain, heat, cold in the skin, and the position of limbs in space. The nerves of the autonomic nervous system regulate the functioning of the various organs of the body that cannot be voluntarily controlled (heart rate, blood pressure, digestion or perspiration).

Diabetic neuropathy is a fairly late complication, at least clinically, and rarely precedes damage to the eye (“retinopathy”). However, in type 2 diabetes, as in most complications, it can be discovered soon after diagnosis, due to the long silent phase of hyperglycemia, but also due to exposure to other frequently associated neurological toxins, such as tobacco or alcohol.

Diabetic neuropathies are a group of disorders that can cause pain, accompanied by numbness, weakness or strange sensations (“paresthesia”). Up to 70% of people with type 1 and type 2 diabetes have some form of neuropathy, which can affect the hands, feet, arms, or legs. Sometimes it can also affect the digestive tract, the heart, or the sexual organs.

What are the signs of diabetic neuropathy?

Some people with diabetic neuropathy have no signs at all. Depending on the type of peripheral or autonomic involvement, the presentations and signs will vary widely.

Damage to the peripheral nerves can take many forms: “polyneuropathy” (damage to all the nerves in a limb) or “mononeuropathy” (damage to a single nerve).

– Diabetic polyneuropathy (“polyneuritis”) usually affects the nerves of the lower extremities. It affects the legs quite symmetrically, starting at the distal end of the longest nerves, i.e. in the feet, and going up the legs.

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This symmetrical diabetic polyneuropathy can manifest itself by a tingling and unpleasant sensation (paresthesia) or numbness in the feet, sometimes by a burning pain or a sensation of electric current and without an obvious cause.

These signs appear gradually, over several months or even years.

Finally, polyneuropathy can lead to a decrease or loss of sensation in the feet, which favors the appearance of ulcers. The motor functions are affected much later because the nerves responsible are better protected and more resistant.

Diabetic mononeuropathy is a condition in which only one peripheral nerve is affected. If several peripheral nerves in different parts of the body are affected, it is called multiple mononeuropathies.

In most cases of a mononeuropathy, it is the nervus cruralis in the thigh (cruralgia) or the nervus medianus in the wrist (carpal tunnel syndrome) that are concerned.

This mononeuropathy usually leads to extreme skin sensitivity (allodynia) and intense burning pain or current sensation with weakness and difficulties in motor control in the affected extremity. Most of the time these signs are sudden.

Autonomic diabetic neuropathy may involve various automatic bodily functions, which may lead to the coexistence of signs that are normally unrelated:

  • dizziness, vertigo or malaise that can lead to a fall, especially when patients suddenly get up from a bed or chair. These are signs of blood pressure that do not adapt quickly enough to get up (orthostatic hypotension).
  • An accelerated heartbeat (tachycardia).
  • A heavy stomach or bloating after meals, with nausea and vomiting associated with reduced stomach motility (gastroparesis).
  • Alternating nocturnal motor diarrhea and constipation associated with a disturbance in the coordination of peristaltic bowel movements.
  • Too much or too little sweating, with skin changes.
  • Difficulties urinating, such as a delayed urge to urinate (loss of sensation in the bladder) or a bladder that does not empty properly (insufficient wall contraction).
  • Erectile dysfunction or vaginal dryness.

What causes diabetic neuropathy?

High blood sugar levels are toxic to nerves and reduce their ability to heal and recover from injuries. Diabetes also damages blood vessels, especially small vessels (microangiopathy). This means that the nerves cannot receive enough oxygen and nutrients to survive. Some people with diabetes will not develop neuropathy even after 20 years. On the other hand, some people with diabetes will develop immediate damage.

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These results suggest that there are independent factors of chronic hyperglycemia in the development of neuropathy. These factors may be genetic and/or related to the environment, especially diet. This would explain a higher prevalence of neuropathy in certain population groups: in India and North Africa, which are more susceptible to nerve damage than others.

What are the factors that could lead to diabetic neuropathy?

Smoking and alcohol consumption can damage small nerves in the hands and feet and exacerbate diabetic peripheral neuropathy.

The same applies to kidney damage, which can occur in diabetes. Some medications can aggravate the neuropathic damage of diabetes.

Age is also a risk factor, and diabetic neuropathy is more common after the age of 65.

The presence of arthritis of the lower limbs is a risk factor, as is vitamin deficiency.

High stature, which is due to longer nerve fibers, is also a risk factor.

What are the complications of diabetic neuropathy?

When nerves are attacked by high blood glucose levels, nerve information circulates poorly and sensitivity decreases. Decreased sensitivity is the most common sign of diabetic neuropathy. It starts at the feet and gradually progresses through the legs.

Because of this decrease in sensitivity, small wounds may go unnoticed and become infected. The skin of the feet also tends to become more fragile, leading to the development of sometimes very deep wounds (plantar puncture wounds).

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At the same time, hyperglycemia weakens the artery walls of the lower limbs, promotes the deposition of cholesterol in the artery walls and contributes to the formation of atheromatous plaque. The accumulation of cholesterol deposits reduces the diameter of the arteries, obstructs the flow of blood and sometimes stops it. The legs and feet are no longer sufficiently supplied with blood, which can lead to pain, but also to wounds such as ulcers that take a long time to heal.

The end result is what doctors call “Charcot foot” a condition that causes weakening of the foot bones which can lead to severe deformities.

How is diabetic neuropathy diagnosed?

The diagnosis is based on the examination taking into account the context (diabetes in development for more than 5 years and poorly controlled). During the examination, the doctor may look for certain signs such as a sudden drop in blood pressure while sitting or standing (orthostatic hypotension) by measuring the pressure while sitting or lying down and then while standing. The following tests can help diagnose diabetic neuropathy and guide treatment:

  • The monofilament test is the simplest sensation test. It involves touching the skin with a small thread: The device exerts constant pressure so that the doctor can compare the sensitivity of the skin in an affected area with the sensitivity in an area without neuropathy (stomach, thigh, etc.). This is often the only test that will be required.
  • Nerve conduction studies using electromyography (EMG) examine whether the electrical signal passes through a nerve and whether the muscles respond well to the nerve signal. In most cases, these tests are not necessary, but they can help to rule out other causes of nerve pain if necessary. It is important to note that in some cases electromyographic changes occur quite late.
  • Quantitative sensitivity analysis can be used in research to quantify changes in neurological impairment over time: sensitivity to light, touch, bite, pressure, vibration, and temperature.

When should diabetic neuropathy be considered?

Nerve damage can be painful at first, but it can also develop silently. It is therefore important to see a doctor regularly so that he or she can detect nerve pain associated with hyperglycemia at an early stage. This way it can be managed quickly to prevent the risk of worsening until it reaches a stage where nothing can be reversed.

Damage to the peripheral nerves can cause strange sensations such as burning, electrical shocks or tingling in the extremities of the hands and feet.

Damage to the autonomic nervous system should be considered in diabetics if blood pressure and heart rate change over time or if there is erectile dysfunction.

What can diabetic neuropathy be confused with?

A neuropathy that occurs in a diabetic can be confused with neuropathy that is related to another cause (10% of cases), which should therefore also be systematically investigated.

When should a doctor be consulted?

A doctor should be consulted if there are strange sensations in the extremities or if there are problems with blood pressure or heart rate, but also with digestive or sexual problems.

What is the treatment for diabetic neuropathy?

The best way to prevent and treat diabetic neuropathy is to strictly control blood sugar levels, which can also prevent other “microvascular” (retinopathy, nephropathy) or “macrovascular” (heart attack, stroke) complications of diabetes.

In most cases, this will mean intensifying antidiabetic treatment with insulin for type 1 diabetes, drugs or even insulin therapy for type 2 diabetes.

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When blood glucose levels are better controlled, some patients find that the pain worsens over time and then decreases.

How is pain treated in diabetic neuropathy?

Conventional analgesics are not usually effective for neurogenic pain, except for morphine in moderate doses, bearing in mind that the aim is to avoid prescribing these drugs for too long because of the risk of addiction and dependency. Tramadol is an interesting molecule because of its double action: action on mu-brain receptors and monoaminergic action at the level of the spinal cord.

Several drugs are being diverted from their original indication because studies have also shown that they are equally effective in controlling pain associated with nerve damage (“neuropathic pain”).

These include tricyclic antidepressants (like amitriptyline or nortriptyline), antidepressants that inhibit the reuptake of serotonin and norepinephrine (like venlafaxine or duloxetine), and gabapentin or pregabalin. The most serious studies have been conducted with these last molecules.

The antidepressants used for neurogenic pain are usually old tricyclic molecules (amitriptyline, clomipramine, imipramine), which have a proven effect on peripheral neurogenic pain. Their side effects are dose-dependent (dry mouth, constipation, sweating, visual disturbances, palpitations, urinary retention, cognitive disorders, confusion, orthostatic hypotension with the risk of falling, especially in the elderly). The effectiveness of selective serotonin and norepinephrine inhibitors (venlafaxine, duloxetine) has been demonstrated in the treatment of diabetes-related peripheral neuropathies (especially duloxetine). The most common side effects of duloxetine include nausea, constipation or diarrhea, loss of appetite, sometimes dry mouth and drowsiness. Some cases of elevated liver enzymes elevated blood pressure, and glycated hemoglobin has been reported.

Among antiepileptic drugs, the efficacy of pregabalin and gabapentin in peripheral and central neurogenic pain in adults is well established. These treatments probably work by reducing central sensitization. The most common side effects include dizziness, drowsiness, fatigue, weight gain, peripheral edema, headache, and dry mouth.

In some cases gels, creams or patches containing a local anesthetic such as lidocaine have been shown to be effective.

Transcutaneous neurostimulation has been shown to be effective in some cases.

Some patients find alternative treatments such as acupuncture or relaxation useful.

To some extent, with blood sugar levels under control, it is possible to stabilize or reverse the complications of diabetes, especially diabetic neuropathy.

What to do in case of complications related to the autonomic nervous system?

There are non-medical measures that can alleviate the most problematic signs of autonomic neuropathy in diabetes:

The slowing of gastric emptying (“gastroparesis”) can be controlled by eating smaller, more frequent, low-fiber and low-fat meals.

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On the other hand, a high-fiber diet and regular water intake can be used to relieve constipation.

In orthostatic hypotension, it is recommended to get up slowly and gradually. Your doctor may advise you to lift your head while lying down or wearing Compression stockings.

If the patient does not feel the need to urinate or empty the bladder, regular toilet visits should be recommended.

If there is a wound or injury to the feet, it is necessary to consult a doctor quickly. Until the consultation, it is recommended to wash the wounds with clean water and to use a colorless disinfectant that allows the appearance of the wound to be seen. Due to the fragility of the skin, a slightly adhesive bandage is preferred (sterile dry bandage, paper bandage, non-elastic tissue dressing).

If the feet are deformed, the doctor may prescribe orthopedic insoles or shoes (or any other type of device) to facilitate the placement of the shoes and to prevent these deformities from worsening.

In some cases, revascularization treatment may be prescribed to restore blood circulation to the lower limbs.

References

https://www.mayoclinic.org/diseases-conditions/diabetic-neuropathy/symptoms-causes/syc-20371580

https://www.ninds.nih.gov/Disorders/All-Disorders/Diabetic-Neuropathy-Information-Page

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