Rina Sheynin, Samantha Fuzailov, Tiffany Huynh, and Julia Zebak explore the root causes, mechanisms, and treatments regarding diabetic neuropathy.
Rina Sheynin, Samantha Fuzailov, Tiffany Huynh, and Julia Zebak
Introduction
About 34.2 million people are living with diabetes today, and of those people, about 6% to 51% have diabetic neuropathy, a debilitating condition characterized by damage to peripheral sensory and motor neurons (U.S. Department of Health and Human Services, 2022; Hicks & Selvin 2019).
The combination of high blood glucose and high levels of triglycerides due to diabetes ultimately results in diabetic neuropathy causing damage to the nerves (Feldman, 2021). There are four main types of diabetic neuropathy that are based on the type of nerves being affected as well as their functions. Their symptoms vary depending on the type and severity of the illness. In peripheral neuropathy, the most common form of diabetic neuropathy, patients commonly suffer nerve damage in the extremities resulting in pain and numbness. In autonomic neuropathy, neurons are damaged, which impacts blood pressure and the digestive system, as well as urinary tract and sympathetic arousal issues (Silva, 2021). In proximal neuropathy (also known as diabetic polyradiculopathy), nerves in the thighs, hips, buttocks, or legs are affected. In some cases, the abdominal and chest area can also be impacted. Other symptoms include weak or shrinking thigh muscles, difficulty rising from a sitting position, and pain in the buttocks, hip or thigh. Mononeuropathy (also known as focal neuropathy) is the type of diabetic neuropathy that occurs when a specific singular nerve is damaged. It can be recognized through a variety of symptoms depending on which nerve is affected (“Mayo Foundation for Medical Education and Research”, 2022).
Main Clinical Manifestations
Diabetic neuropathy can manifest in a variety of ways that affect both the physical and mental quality of life of those affected. First signs of disease include numbness and tingling of the extremities, starting in the feet and spreading to the legs. This numbness can prove to be debilitating leading to falls that can cause more injuries (Callaghan et al, 2012). People with diabetic neuropathy can lose the ability to feel temperature, pressure, vibration, and joint or body positioning(proprioception). These losses can also be followed by a loss of reflexes, especially in the ankles (Feldman et al, 2019). People affected by diabetic neuropathy can develop intense sharp, burning, or freezing pain sensations resulting in the amputation of limbs that are affected by it (Callaghan et al, 2012).
Causes
Diabetic neuropathy has numerous different reasons for occurring in the body and results in damage to the nerves of the peripheral nervous system. The timeline for the onset of diabetic neuropathy varies. Some patients have a more rapid onset, while others may not recognize symptoms for years. Research shows that about 50% of people who have type II diabetes and about 28% of those with diabetes type I will have neuropathy (Cristian and Remus, 2018). When a patient has hyperglycemia, cells including Schwann cells and neurons of the peripheral nervous system cannot function efficiently and can impair the Na+/K+ ATPase pump function. This could result in neurons not being able to communicate and send messages to effectors. Additionally, neuropathy can cause overactive microglia which causes further inflammation and pain for the patient (Krishnan, 2008).
Neuropathy can be classified into three groups based on how the nerves are affected: mononeuropathy (a single nerve), multifocal neuropathy (multiple nerves in a specific area), and polyneuropathy (multiple nerves throughout the body) (Hammi, 2022). Diabetic Neuropathy can also be divided into four types: peripheral, proximal, autonomic, and focal neuropathy.
Peripheral neuropathy affects the nerves extending to the upper and lower extremities. This is the most common type of diabetic neuropathy due to the sheer length of the nerves, which makes them more susceptible to damage. Proximal neuropathy affects the muscles of the hips and upper legs. Autonomic neuropathy affects both the autonomic nervous system, due to nerve damage, and the different body systems such as the cardiac and respiratory systems (Silva, 2021). Lastly, focal neuropathy affects the nerves in the head, most often the optic nerve (cranial nerve II). There are also other causes of diabetic neuropathy such as traumatic incidents, infections, and autoimmune disorders.
Treatments
While there is no known cure for diabetic neuropathy at this time, a number of treatments are available to improve the impact of symptoms on patients’ lives. Treatments for diabetic neuropathy include close monitoring of blood sugar levels through administration of insulin or oral medication, changes to diet, exercise, pain control, and foot care to prevent further complications due to the condition. Symptoms of pain and burning from diabetic neuropathy may subside when blood glucose levels improve. Currently, several FDA approved medications for the treatment of diabetic neuropathy do exist. (Feldman, 2021).
Discussion
Diabetic neuropathy can cause different mechanisms of injury to peripheral nerves. One type of reaction is segmental demyelination, which is the degradation of the outer covering of the neuron called the myelin sheath, but not of the axon itself (Hammi & Yeung, 2022). The myelin sheath allows for fast conduction of action potentials because it is an insulator and the sodium/potassium channels would only need to open in the space between the myelin sheath (called Nodes of Ranvier) (Williamson & Lyons, 2018). Therefore, degradation of myelin will slow down the conduction of nerve impulses and cause impairment to the normal functioning of the body. Diabetic neuropathy can also cause axonal degradation, starting distally (Hammi & Yeung, 2022). Axon degradation occurs because of the dysfunction of Schwann cells and neurons as mentioned earlier. Schwann cells also play a role in the development, maintenance, function, and regeneration of axons (Jessen, 2016). Damage to the axon means that no signals can be sent to the effectors. Wallerian degeneration can also occur in patients with diabetic neuropathy. Wallerian degeneration is when the distal axons waste away because of the degradation of nerve cells (Hammi & Yeung, 2022). All of these mechanisms of injury can affect the signaling of the peripheral nervous system.
The disruption of signaling in the peripheral nervous system can negatively impact everyday functioning. As mentioned previously, nerve damage can cause tingling and pain, as well as a loss of sensation in feet. Since signals can’t reach nociceptors, which are sensory receptors for pain, patients are more prone to blisters and cuts (U.S. Department of Health and Human Services, 2018). In addition, the feet are less likely to heal from sores and infections because there is decreased blood flow, which can lead to gangrene (the death of tissues) (U.S. Department of Health and Human Services, 2017). Diabetic neuropathy can also cause problems with the autonomic nervous system. Nerves may respond more slowly to changes in the body’s position, stress, physical activity, sleep, and breathing patterns if the nerves that control heart rate and blood pressure are damaged. Damage to nerves in organs can also impair their functioning. For example, it can cause vomiting (digestive system), the inability of the bladder to know when it is full or empty (urinary system), and weaker stimulation in sex organs. Diabetic neuropathy can also cause damage to the nerves of the eyes, as well as the nerves of the sweat glands, making it much harder for the body to thermoregulate (U.S. Department of Health and Human Services, 2018). Diabetic neuropathy can cause a variety of problems with the normal functioning of the body. Therefore diabetes, the root cause of diabetic neuropathy, should be treated promptly.
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