Diabetes is a disorder of sugar metabolism which affects almost all organ systems of the human body. Neuropathies are the most common complication of uncontrolled diabetes or long standing diabetes. With inadequate glycemic control up to 75% of patients can evolve neuropathies in 2 years’ time as well in type 1 as in type 2 diabetes mellitus.
The occurrence or the medically pathophysiology of diabetic peripheral neuropathy is a complex process. There are many theories regarding the pathophysiology. Most of the scientists accept that it is a multifactorial or there are many contributing factors for the occurrence of diabetic peripheral neuropathy. The primary factor is existing, persistent and uncontrolled hyperglycemia.
As any other tissue in human body, nerves are also made of cells. The nerve cells are called neurons. Neurons also depend on oxygen and glucose for their survival. Glucose metabolism associated with oxygen gives energy for the functions and survival of neuron cells. If the neuron cells function properly then the as a whole unit the nerve functions well. Alteration of this function is the disease of nerves thus neuropathy.
Persistent hyperglycemia increases the sugar metabolism pathways in peripheral nerves which in return increases the sugar levels inside the neuron cells. Mainly sugars such as sorbitol and fructose accumulate inside the neuron and they damage the neuron cells. This damage results in reduced enzyme activities inside the neuron which results in accumulation of various ions inside neurons such as sodium. When sodium accumulates inside it draws water in to the cells and cause cell to swell. This swelling causes the cell damage which is usually irreversible. It causes nerve degeneration thus causing the neuropathy.
Immune Mechanisms which involves the various types of white blood cells and other chemicals released by the white blood cells and human immune system may be responsible for the diabetic peripheral neuropathy. In general our immune system makes various chemicals such as antibodies and cytokines to destroy harmful microbes and other harmful cells such as cancer cells. But in patients with diabetes mellitus it is a known factor that their nerve cells are covered with chemicals which signals the immune system to attack them. Then the white blood cells, antibodies and various other chemicals attack the neurons and destroy them. It results in nerve degeneration and results in diabetic peripheral neuropathy.
Chronic micro-vascular ischemia
Chronic micro vascular ischemia or Insufficiency or lack of blood supply to the nerves is another process of occurring diabetic peripheral neuropathy. Nerves have small blood vessels to supply blood. These blood vessels are called “vasa nervorum.” They run long with the nerves. They have very small caliber and can be blocked easily. Blocking of the blood vessels is mainly caused by the thickening of the vessel walls. When there is hyperglycemia the blood sugar levels are elevated beyond normal limits. It causes the sugar or the glucose to bind with various blood cells and other proteins in the blood. After binding, glucose makes various complexes with the bound products. These products are heavy and when they circulate through the vessels they tend to deposit along the wall and it makes the wall thickened. Thickening of the wall makes the blood vessel lumen to become narrow.
When the blood vessel lumen becomes narrowed the circulation of the blood is diminished and causes lack of nutrients and glucose to the nerves. It results in nerve damage and nerve degeneration which leads to diabetic peripheral neuropathy. It has been found that 95% of chronic diabetic patients have long standing ischemia to the nerves.
Growth Factor Deficiency
Growth Factor Deficiency is another proven cause of diabetic peripheral neuropathy. Growth factors are essential for the growth, maintenance, survival and regeneration of nerves. From various mechanism mentioned above the nerves get damaged in daily basis. For the repairing process growth factors are essential and lack of these may lead to irreversible damage and nerve degeneration.
Mechanism of pain in diabetic peripheral neuropathy
Pain is one of the most adverse outcomes of diabetic peripheral neuropathy. It significantly reduces the number of activities of daily living and reduces the quality of life. Pain is an unpleasant felling perceived by our brain for many harmful stimuli. Stimuli are transferred via the nerves and when the neuron circuit is malfunctioning it can lead to false stimuli and can cause various pain syndromes. Read for more information about The Neuropathy Solution or see our review.
The causes for many pain syndromes differ from each other and the pathology may be presented in various parts of the peripheral nervous system. It can include nerve branches, nerve terminals, Axons, Synapses, Spinal cord and associated nerve tracts and peripheral neuronal ganglions. These convey the messages to pain center and activate the pain. It is more pronounced in patients with uncontrolled, long term severe hyperglycemia. There are many treatments for the pain but the main stay remains as good glycemic control.