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Auto-Immune Diseases

Auto-Immune Diseases: Type I Diabetes

Autoimmune diseases occur when the immune system attacks healthy cells in the body.

It seems counter-productive for our immune system to attack our own bodies, but scientists think that there is a naturally occurring level of autoimmunity that is going on all the time in humans and other higher animals. When this autoimmunity starts to harm the body it is called an autoimmune disease. Scientists still don’t completely understand why the immune system does this and why only certain individuals are affected while others are not, but they can draw many conclusions:  genetics, drugs, viruses, and certain chemicals all seem to be associated with autoimmune disease.

There are over 80 different types of immune disorders, but some of the most common are Lupus Erythematosus, thyroid disorder, Mutliple Sclerosis, arthritis, celiac disease, and Type I Diabetes, to name a few. Some of these diseases affect only a specific organ or tissue in the body, so they are localized; others can affect the whole body, and are termed systemic.  Localized diseases attack a specific area of the body, like tissues and joints, the nervous system, the blood, and the pancreas for example.  Metabolism, muscular movement, brain function—these are just some of the body’s major functions that can be de-regulated by autoimmune disorders.  The body is a highly interconnected system, so once one organ or individual system is attacked, the autoimmune disease can damage and de-regulate many other functions of the body. 

Type I Diabetes is an autoimmune disease where a rare error occurs and the immune cells attack some special cells in the pancreas.

Autoimmune diseases have a tendency to be more prevalent in women than in men.  About 75% of autoimmune diseases affect women. Some scientists believe that women have more complex immune systems than men, and so are more susceptible to complications, usually set off by pregnancy.

Biology of Pancreas and Insulin (Type I Diabetes)

Xray
Cells in the pancreas produce insulin, without which our cells can not get sugar from the blood stream.

All living things, and all the cells that compose them, need energy to survive. Metabolism refers to all the processes of the body that involve getting and/or spending energy. So, metabolism includes eating food, digesting it and breaking it down into nutrients, getting the nutrients to each cell of the body and each cell’s processes that utilizes this food energy.

The best sources of energy for our body are sugars (carbohydrates), fats and proteins in our food. But not all sugars and fats are equally healthy! For example, highly processed sugars like those found in most candy and soda are harder to digest by the body. 

Digestion is the process through which your body consumes food, and breaks it down to its basic components of sugars, fats proteins and other nutrients. The nutrients are absorbed into the body mostly while passing through your intestine.  The nutrients are taken by the blood vessels to all cells and in your body, that they may get all the energy they need. Digestion is a very complicated process that involves many cells, tissues and organs working together to ensure the most efficient harvesting of energy! Many special organs evolved to help this process become more efficient, like the liver which stores sugars in a special form, and the pancreas.

Diabetes is an auto-immune disease.
Inside the pancreas we find the islet cells (in yellow), surrounded by a capillary. In diabetes, white cells get confused and attack these cells.

The pancreas is an organ in your body located directly below the stomach and liver. It is a vital component of the digestive system, carrying out two main functions:  producing enzymes that digest food in your intestine and secreting hormones that regulate the sugar levels in your blood. 

The crucial step that falters in diabetes is one of the last: getting the ingested sugar from the blood to inside each cell!

Learn more about the difference between sugar and sugar and how it all relates to metabolism here >>

Anytime you eat foods that are high in sugar content, like breads, cereals, fruits, and candy, you increase the level of sugar—in the form of glucose— that is circulating in your blood. In non-diabetics, there are special cells (beta cells) in the pancreas that secrete a hormone called insulin. Insulin is very important because it regulates the transport of sugar from the blood into the individual cells, where it is converted into a form that can be used for energy.  Without insulin, no matter how much food you eat, your cells would still starve. 

But in Type I Diabetics, the insulin-making cells are destroyed by the immune system, leaving the body without insulin to regulate glucose levels in the blood. Too much blood sugar can cause hyperglycemia, and if left unregulated, hyperglycemia can lead to many other serious health problems.  That is why it is important for Type I Diabetics to supply the body with the insulin that it can’t produce by itself. 

What is Diabetes Type I

Type I Diabetes affects approximately 5% to 10% of the general population, and it usually sets in during childhood. No one can say for sure what triggers Type I Diabetes, but scientists believe genetics and environmental factors play a role.  Similar to many other autoimmune disorders, if someone has family members that are diabetic, they have a greater chance of developing Diabetes than someone who has no family history of Diabetes.

Environmental factors, like certain chemicals and viral infections, are believed to initiate or exacerbate Type I Diabetes. Also, there is evidence linking Type I Diabetes to other autoimmune diseases like anemia, thyroid disease, and Addison’s disease.

Pathogenesis: what actually happens?
In Type I Diabetes, the special insulin-producing cells of the pancreas—the beta Islet cells—are attacked and destroyed by the body’s T cells. The immune system becomes intolerant [link to page that discusses memory/tolerance/intolerance)to certain cells of its own body, the Islet cells, and begins to produce antibodies against it.  This then is an auto (against the self) immune (immune response) disease.

It is very unusual for the body to mistake healthy cells for infected ones. There are many steps taken to prevent this. T cells are the mediators and regulators of the immune system. They activate the antibody response and stimulate phagocytosis.  If they mistakenly recognize healthy body cells as infected, they activate other cells of the body to attack as well.  To prevent this, when T cells are maturing in the thymus, they are evaluated before they are released into the body. If they are designed to recognize and attack body cells, then they are automatically destroyed—nearly 90% of T cells are destroyed in the thymus before traveling to the body! 

Does the thymus release irregular T cells into the body? The next page outlines some major theories behind the origin of Type I Diabetes.

Diabetes Type I: Possible Causes

Diabetes Type I is not a new disease. There are records of Type I Diabetes existing in ancient Egypt. Today, there are several explanations being considered, including viruses, drugs, and chemicals. But there is significant evidence that Type I Diabetes usually results from a combination of both pre-disposed genetics and environmental factors.

Environmental Factors

Viruses
There is considerable evidence that viruses induce Type I Diabetes, as well as some other autoimmune disorders. Our immune system works by recognizing the shape of the proteins on the surface of cells and other particles. When viruses infect cells in the body, they cause the cells to produce abnormal proteins. Our immune system learns to recognize these abnormal proteins and uses them to target the infected cells and repress the infection. Scientists think that in the case of diabetes, a particular virus enters the body that causes cells to create abnormal proteins that are similar to the proteins of the insulin-making cells.  So as the immune system starts to respond, the immune cells also mistakenly recognize the healthy pancreas cells, and start to attack them.

This concept is called molecular mimicry, because healthy cells “mimic” the surface proteins of viruses, causing T cells to attack. Some of these viruses are relatively common: coxsackie and rota viruses which commonly cause intestinal infections in infants and children, and others like the viruses that cause rubella and mumps.

Chemicals and Drugs
Another theory is that some preservatives found in certain foods cause Type I Diabetes. Nitrosamines, a nitrite preservative that can be found in some meat and cheese products, as well as fish, fish byproducts, and pesticides are known carcinogens in both humans and animals, and they are currently being linked to Type I Diabetes.

Cow’s milk has also been associated with Type I Diabetes onset.

Researchers in Finland carried out studies that positively linked babies with Type I Diabetic parents and cow’s milk. They suggest that the immune system can attack the Insulin hormone found in cow’s milk, and can then turn mistakenly to attack human pancreatic insulin-making cells. Although there is not yet enough research to make substantial claims connecting cow’s milk and Type I Diabetes, this study does highlight the connection between genetic predisposition and environmental factors.

The drug Streptozotocin, derived from a soil bacteria, is a proven cause of Type I Diabetes. It directly destroys Islet cells, and so today is only used to treat pancreatic cancers. First introduced in antibiotic form in the 1950’s, it was not known as a cause of Diabetes until the 1960's. Animal studies indicate that drugs containing alloxan destroys Islet cells in the pancreas, and is used to induce Type I Diabetes in laboratory rodents. Thiazide diuretics are also linked to Type I Diabetes.

Genetics
Just because someone's parent has Type I Diabetes does not mean he or she is guaranteed to inherit the disease, but chances are much higher than children of non-Diabetic parents. Why is this? Researchers have a few ideas. Scientists have located the gene sequence that codes for the surface proteins on the insuling-making cells that T cells mistakenly read as signs of infected cells.

Current Research:
Read more about gene mutations that can lead to Diabetes Type I here.

Another cause could be mutations of genes that dictate certain cells in the immune system. One specific gene controls the reactivity of certain molecules of the immune system, the cytokines. The mutated gene increases the reactivity of the cytokines, and so causes the destruction of the Islet cells.  Scientists believe that gene mutations linked to Type I Diabetes are also responsible for the onset of additional autoimmune diseases, like lupus and arthritis.

Modern Treatments for Diabetes Type I

There is currently no cure for diabetes, but there are a few available treatments, and a lot of options being researched! Right now, there are two popular types of treatment for patients with Type I Diabetes. These are insulin replacement therapy and islet cell transplant.

Insulin Replacement Therapy

The majority of individuals that live with Type I Diabetes undergo insulin replacement therapy. This means that everyday, many times a day, they must inject a very specific amount of insulin into their blood streams. This insulin makes up for what their dead insulin-making cells cannot produce. 

Although many diabetic patients can lead healthy lives with insulin replacement therapy, it is a very painstaking method to treat the disease. Despite having to constantly monitor blood sugar levels and administer many shots daily, sometimes this treatment is not effective enough.  It is difficult to imitate the very delicate balance of the pancreas.  If the shot contains too little or too much insulin, or a shot is missed, the patient runs the risk of developing further health complications.

Islet Cell Transplant

Instead of constantly supplying the body with insulin, some doctors are bypassing insulin injection in favor of transplanting new islet cells or even a new pancreas into the diabetic patient. Doing so could potentially replace the insulin-producing islet cells and restore the body’s metabolism of glucose.  Islet cells can be transplanted into the liver, where they are able to produce insulin.  Recent studies show that one year after the operation, 58% of Islet cell transplant patients were insulin independent. But there are many problems with this method. But not only is this a very costly procedure, it often takes two or more donors for a successful transplant, so there is a long waiting list.  Also, the transplanted islet cells can fail to function after a few years. But the biggest risk is that the transplant can be attacked by the immune system—this is called rejection.

Rejection is a risk with all transplants. Any cells that are transplanted into one person’s body from another person’s are very likely to be attacked by the white blood cells of your immune system. They recognize the cells as foreign, and so will again destroy the islet cells! To counteract rejection, transplant patients must take immunosuppressant drugs for the rest of their lives to allow their new islet cells to function.  Immunosuppressant drugs usually weaken the whole immune system, and so the patient experiences fatigue and sickness, and is likely to develop other health problems.  Sometimes it is better for the diabetic patient to avoid transplants.

So current treatment methods like islet cell transplants and insulin injection both can help the diabetic patient, but they cannot cure the disease. Scientists are now looking to regenerative medicine for the answers!

Regenerative Medicine Treatments

Modern medicine offers a few options to help alleviate the symptoms of diabetes but as of now it doesn't offer a cure. So, researchers are looking for headway in the relatively new and promising field of regenerative medicine.   Instead of replacing cells and organs in sick individuals, the idea is to regenerate those cells or organs, or in other words, to re-grow the body’s own natural cells that were destroyed.  In patients with Type I Diabetes, scientists are studying how to regenerate the insulin-producing islet cells of the pancreas.

Stem Cells

The key to re-growing cells is to use stem cells. Stem cells are special self-renewing cells found in certain areas in the body that mature into different cells, organs, tissues, and muscles. 

Current Research:
Read more about the study that studies making islet cells from brain stem cells here.

Scientists are experimenting with harvesting and cultivating stem cells that could mature into islet cells, and then transplanting them into patients with Type I Diabetes - an islet cell transplant!  For example, some researchers at Stanford University believe that stem cells from the brain can mature into islet cells. 

But even with new insulin-producing cells derived from the individual’s own body, an auto immune reaction against them is still a problem.  The nature of autoimmune diabetes Type I is that the body already attacked its own cells, so its T cells and other white blood cells are still programmed to attack these new cells.  Instead of taking immunosuppressant drugs, which are damaging to the body, scientists are developing two methods to resolve this problem.  

One is to place the re-grown beta cells into special protective capsules that would not allow the immune system to detect the cells.  The capsules would be designed to let insulin out and allow blood sugar in. 

Another idea is to “shave” off the proteins on the surface of the insulin-making cells that seem to be activating the autoimmune reaction. Because cells use the proteins on their surfaces to read each other and take specific actions from these signals, the proteins on beta cells could be responsible for telling T cells to attack the insulin-producing cells. Getting rid of some of these proteins might prevent the immune system from attacking.

Hopefully, scientists will soon be able to create insulin-producing cells from stem cells as well as prevent an autoimmune reaction, and cure people with Type I Diabetes.

Diabetes Type II

It is estimated that over 200 million people in the world today are living with Type II Diabetes, significantly more than those with Type I Diabetes.  Although Type II Diabetes has some of the similar effects of Type I, its cause is very different from Type I Diabetes.  Type II is not an autoimmune disorder nor it is it connected to autoimmunity. In Type II Diabetes the body also can’t use insulin properly, but instead of being unable to produce it, the body seems to produce too much.

Learn more about Type II at the American Diabetes Association and at the Medical Encyclopedia.

Diabetes Type II is not well understood yet but doctors agree that a few things seem to be associated with it like hyperglycemia (too much sugar in the blood) and insulin resistance. The latter, insulin resistance, is when cells in certain tissues, like the muscle, liver and fat cells, stop responding to insulin in the body.  This can result in both insulin and sugar accumulating in the blood! Too much insulin and glucose in the blood can become toxic. Also, if the cells don’t take up enough sugar either, the cells starve. These problems over time can affect the health of whole organs and leave the individual very weakened.

Studies indicate Type II Diabetes is linked to genetics, environmental factors, diet and lifestyle, and is specifically linked to obesity.

Type II Diabetes develops over time, and seems to affect more older adults, the overweight, and some ethnic groups. Although there are more and more cases of Type II Diabetes affecting children, and even individuals who are not overweight. But doctors agree that this type of diabetes can be controlled and even prevented through diet, exercise, and regular medical check ups. 

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