The Nerve Damage of Diabetes Mellitus

Diabetes has become a very common part of our vocabulary nowadays. We know that it is a disease caused by the malfunctioning of the pancreas and also the malfunctioning of receptors in our cells. We know that there is a high chance of getting hyperglycemia (too much sugar in the blood) or hypoglycemia (too little blood sugar), and that the disease can sometimes lead to mood problems if not taken care of. However, there are many other side effects. One is the numbing of the hands and feet, along with diminished eyesight, or even blindness. Another is the increased risk of dementia. A lot of these side effects are neurological and vascular, and due to there being a lack of something occurring, we can assume nerve death or at least damage. So what is it about diabetes that causes this nerve damage? Is it the fluctuation of sugar in the blood, and thus amount of sugar in the cell? There are many theories on this
According to the National Diabetes Information Clearinghouse, about 8% of the population, nearly 24 million people, have diabetes in the United States. However, Diabetes is becoming a worldwide Pandemic, seen in almost every country. According to the World Health Organization (WHO), in 2000 there were 171 million people with diabetes, and it has been estimated that in the year 2030 to be 366 million, doubling in the next 2 decades. There are more women than men with diabetes, and majority of diabetic occurrence is in the age range of the population above the age of 65 (5). However, there are also many people born with the disease or becoming diagnosed with it early on. As such, these are the people that see the long term effects of diabetes.
A major long term effect of diabetes is a disease called diabetic neuropathy. There are several types of neuropathies, but they all fall under the category of either peripheral or autonomic. Peripheral neuropathies affect the peripheral nerves, such as in the arms and legs, while autonomic neuropathy affects organs such as the heart, liver, kidneys and sex organs (1). While both these categories of neuropathies indicate nerve damage, no one is exactly sure as to how diabetes causes the nerve damage. One hypothesis is that it is the lack of insulin in the blood is a cause (2). Another is that in pre-diabetics (people who may be obese and generally have a usual blood sugar range considered above normal, but not diabetic) and insulin-resistant diabetics, there is an overproduction and stimulation of insulin in the body that causes the nerve damage (2). Also, it could be that not enough glucose is going into the cells for the cell to function properly, and thus the nerve terminal dies and the cell body dies (3).
Diabetic neuropathy can range from unnoticeable to excruciatingly painful. In fact, some people may not even be aware that they have it and must be diagnosed by a doctor, while other experience a lot of pain in the muscles and have trouble moving. There are also many risks with neuropathies. For example, a person who has a type of autonomic neuropathy may not be able to realize that they have hypoglycemia, or low blood sugar. Usually, a person realizes that their sugar is low because their body shows symptoms of it, such as dizziness, shaking, nausea, and sweating. However, a neuropath with hypoglycemia unawareness would not realize it and thus they can pass out, and even go into shock or a coma if not tended to immediately. Another very major risk and prognosis of peripheral neuropathy can be ulcers in the legs, and eventual amputation of limbs. When this occurs, there is not enough nutrients and oxygen going to the limbs, and this leads to muscle atrophy and decomposition. However, a lot of these fairly frightening side effects of diabetes can be prevented.
There are many ways to treat neuropathies, but it all depends on controlling blood glucose levels and insulin support (some patients take oral medications such as Type II diabetics, while others take shots, like Type I diabetics). Neuropathies generally can be seen in long-term diabetics, such as those who had the disease for over 25 years. It generally does occur in all diabetics, but controlling blood sugar prolongs it. There are many therapies for peripheral neuropathy, such as giving pain medication, taking antidepressants or anticonvulsants. These usually dull the symptoms, and can help regulate the neuropathy a little. Also, some treatments can be applied to the skin, such as capsaicin cream, along with herbal remedies such as primrose oil. Acupuncture, biofeedback and physical therapy can also help with peripheral neuropathies. As with peripheral neuropathies, it again depends on the type of autonomic neuropathy the person has to deem a type of treatment. For example, medication can be used, such as with gastrointestinal, hepatic or cardiac problems. Also, simple lifestyle changes such as avoiding fatty foods and eating smaller meals more often can improve digestion, just like standing or sitting up slowly can prevent dizziness or fainting due to blood pressure changes (1). While diabetic neuropathy is a major side effect of diabetes, another side effect, generally seen in long term diabetics, is the increased prevalence of dementia.
As pointed out earlier, diabetes causes nerve damage. Nerves are generally associated with the brain so of course we can assume that diabetes has some effect on the brain. One thing seems to be a lot of cell death, with leads to cognitive decline (4). His cognitive decline can lead to dementia, where a person progressively loses social and cognitive abilities, until the person is eventually completely dependent on others for even the most basic care. Insulin is said to regulate the synaptic plasticity in the cortex and hippocampus, which are regions of the brain generally associated with learning and memory. However, for people with insulin resistant diabetes (Type II) insulin cannot really get into the neurons in these regions of the brain, and not play its part in the plasticity. Also, insulin also plays a role in neuronal cell survival, as seen in cultured cortical neurons where it protect the cells against serum-deprivation induced apoptosis, or cell suicide (2). And it has been shown that in diabetics with dementia, there is excessive neuronal cell death.
Insulin interacts with cells to help the cells receive glucose for proper cellular respiration, or functioning. However, if the insulin is not there, or the cells are resistant to the insulin, then it is very difficult for the cells to function well, and thus they may end up using up other resources such as fat and protein. This can lead to extreme weight loss and ketonuresis, where proteins are broken down by the body for energy. A possible side effect of the increased blood glucose levels in diabetics could be increased blood pressure. Constant pressure to vascular walls expands them, and this makes it very difficult for blood to circulate quickly around the body, especially regions far away from the core, such as the legs and feet. While insulin has many benefits aside from regulating sugar control, perhaps it is the increase in blood sugar and not quite the insulin deficiency or resistance that is leading to poor cell functioning, thus leading to cell death by not being properly oxygenated or nutrient enriched due to slower circulation of blood. The cells that usually die, either via neuropathy or dementia use a large amount of glucose in their metabolic activities, which can correlate with my own hypothesis.
Diabetes is becoming a fairly common problem, and as we do not have a cure for the disease yet, the best we can do is try to manage it. For that, there are many treatments. For Type I diabetes, also known as insulin dependent diabetes, there are many kinds of insulin that people can take through shots and through an insulin pump. For Type II diabetes, or insulin resistant diabetes, people can take oral medication, the most common known as Metformin, to control insulin functioning or help the insulin reach the cell receptors. Doctors also encourage diet control and exercise to control blood sugar levels, and continuously checking the blood glucose levels through a blood sugar checking machine.
There may not be a cure yet for the disease, but the scientific world is continuously working to find a cure. A possible treatment that has been performed in India is actually replacing the pancreas, which is the gland that plays a key role in glucose level control, by secreting insulin and glucagon (when the body's blood sugar is low in a normal person, the pancreas secretes glucagon, which works to bring out the sugar stored in organs, such as in the liver, to raise blood sugar levels). This seems like a reasonable cure but the body may end up rejecting the new pancreas, so I feel that more stem cell research may be needed to remove the mutation out the pancreas cells and recreate one based on the individual's own genes. This may work as a possible cure.

 

 

 

 

 

 

 

 

 

 

 

 

 

References

(1) NIH, Diabetic Neuropathies: The Nerve Damage of Diabetes, February 2009
(2) A.R Cole et al, Molecular connexions between dementia and diabetes, Neuroscience and Behavioral Reviews, vol 31, April 2007
(3) N. Ranji et al, Does Diabetes mellitus target motor neurons?, Neurobiology of Disease, vol 26, 310-311, November 2006
(4) D. Bruce et al, Predictors of Cognitive Decline in Older Individuals with Diabetes, Diabetes Care , volume 31, number 11, November 2008
(5) S. Wilde et al, Global Prevalence of Diabetes: Estimates for the year 2000 and projections for the year 2030, Diabetes Care, Volume 27, Number 5, May 2004.