Immunotherapy: A Potential Treatment for Type 1 Diabetes
An Autoimmune Problem
Type 1 diabetes is a major autoimmune disorder that can be managed but not cured. The patient’s immune system attacks the pancreas and stops it from making insulin, a vital hormone. Insulin from another source must be given to the patient in order for them to survive. Although the substitution often works well, it's not a perfect solution for the problem. In an exciting development, researchers have been able to stop the attack of the immune system in test subjects newly diagnosed with type 1 diabetes. The process that they’ve discovered may prevent further damage to the pancreas.
The term “immunotherapy” means modifying the action of the immune system is order to treat disease. It’s often used in reference to cancer treatment, which is another exciting application of the therapy. Researchers from King’s College London and Cardiff University have published the results of a clinical trial which shows that the therapy also has potential in the treatment of Type 1 diabetes.
Having one or more of the symptoms listed above doesn't necessarily mean that a person has diabetes. A doctor should be consulted for a diagnosis and treatment recommendations. Polydipsia is excessive thirst; polyphagia is excessive hunger; polyuria is excessive urine production; and glycosuria is an excessive amount of sugar in the urine.
The Pancreas and Insulin
The pancreas is located in the abdomen behind the stomach. It's a narrow and elongated organ that produces both hormones and digestive enzymes. The hormones are produced in areas called pancreatic islets or islets of Langerhans. Once they're made, they are secreted into the bloodstream. Insulin is produced by the beta cells in the islets. The acini produce the digestive enzymes. These are secreted into ducts that lead to the small intestine.
The function of insulin is to control the blood sugar level. Blood "sugar" is actually glucose, a chemical that our cells use for energy production. It's important that the blood sugar level stays relatively constant in order to keep the cells of the body healthy. Both a high and a low blood sugar can be harmful.
A Description of Type 1 Diabetes
The incidence of type 1 diabetes in Europe has been rising by about 4 per cent each year, particularly in children and teenagers.— Rachel Baxter, New Scientist
Autoimmunity and Type 1 Diabetes
Our immune system is normally very helpful in our lives. When it's weakened, we have a high risk of getting sick. The system attacks and destroys pathogens (microbes that cause disease), such as bacteria, fungi, and viruses.
In some people the immune system misbehaves and attacks the body's own cells. This mistake can cause an autoimmune disease—one produced by the person's own immune system instead of by a pathogen. In type 1 diabetes, the immune system attacks the beta cells in the pancreas and destroys them.
The leader of the recent clinical trial says that the immune system doesn't destroy all of the beta cells at the same time. People just diagnosed with type 1 diabetes and in the early stage of the disease "typically" have as many as 15% to 20% of their beta cells left. This is a key point in the success of the trial.
Researchers have noticed that the incidence of type 1 diabetes is increasing in several areas. The explanation for this observation is unknown. The disease is most common in children but can occur in people of any age.
A Day in the Life of One Person With Type 1 Diabetes
In a healthy pancreas, the amount of insulin that's secreted varies throughout the day (and night). It depends on a variety of factors, including the amount, type, and frequency of food that's eaten and the vigour, length, and frequency of exercise. It's hard to be as precise as the body's natural mechanism for regulating blood sugar when supplemental insulin is used.
A person with diabetes measures their blood sugar level and sends insulin into their body multiple times during a day. Injections, an insulin pen, or an insulin pump are used to deliver the hormone. Even with treatment, a patient may experience periods when their blood sugar is higher or lower than it should be. Both of these conditions can be harmful to the body if they are extreme or if they are milder but occur frequently or continuously over time. Night time can be especially problematic for a patient.
Improved devices for measuring a patient's blood sugar and injecting insulin are being created. The goal is to create a device that automatically and frequently measures the blood sugar level and then injects the correct amount of insulin or of glucagon, another hormone that influences the amount of glucose in the blood.
Even though insulin treatment may be successful for many years, the patient may eventually develop serious and sometimes life threatening complications. These complications include eye, nerve, cardiovascular, and kidney problems.
One of my acquaintances developed type 1 diabetes as a child. Sadly, she recently died in middle age from complications of the disorder. People with the disease have an average lifespan of about ten to twelve years shorter than a healthy person. This is an average value, which means that some people live for a longer time and others for a shorter one. We need improved treatments for the disease, or better still, a cure and a way to prevent it.
The Clinical Trial and Its Results
The results of the recent clinical trial are impressive. The trial involved a relatively small number of people, however. The subjects were adults and had been diagnosed with type 1 diabetes in the last 100 days. 21 people were periodically injected with a proinsulin peptide. A peptide consists of a short chain of amino acids. The peptide was given its name because it supports the production of insulin. 8 people in the trial were periodically injected with a saline solution without the peptide. This solution acted as a placebo. A placebo is an inactive and harmless substance.
The injections continued for six months but data was collected from the patients for twelve months. Over the course of the year, the patients given the peptide had no need to increase the amount of insulin that they received. The patients in the placebo group needed to increase the amount of their supplementary insulin by 50%. In addition, the group given the peptide contained roughly the same level of C-peptide in their bloodstream throughout the year. This chemical is used in the production of insulin by the pancreas. In the patients given the placebo, the level of C-protein declined significantly during the year, suggesting that their pancreas was becoming less active.
The administration of the peptide seems to have reset the immune system, stopping its abnormal behaviour and preventing further beta cell destruction. It would be interesting to see the results of an experiment performed with a larger number of people. It would also be interesting to see if the beneficial effects of the peptide last for longer than a year.
Type 1 diabetes arises due to misbehaving T cells, or T lymphocytes. The cells are a very important and normally very helpful component of the immune system. In type 1 diabetes, however, T cells attack and destroy the beta cells in the pancreas. The proinsulin peptide interferes with the action of the misbehaving T cells.
Good T Cells Go Bad in Type 1 Diabetes
Double Blind Experiments and Placebo Use in Clinical Trials
The peptide experiment was double blind. In this type of experiment, neither the person administering the treatment nor the subject knows whether the treatment is the one being tested or a placebo. In order for this to work, the test treatment and the placebo must appear to be identical.
A double blind experiment prevents any unconscious influence of the administrator on the results of the experiment. It also prevents any bias in their interpretation of the results. A blind experiment is also important for the subject. A person may feel better if they know that they are being given a treatment because they believe that the treatment will help them. If they don't know whether they are being given the treatment or the placebo, the chance of this effect is reduced.
Placebos are used in experiments even when it's unlikely that simply believing that they will be helped will be beneficial for the patient. A patient may improve during a clinical trial for an unexpected reason, such as the body's natural healing process over time or a factor that the researcher hasn't considered. Comparing the results of a test group and a placebo group can show whether a treatment is helpful or whether an improvement is due solely to another factor. If the subjects in the group that received the treatment show a significantly better result than those in the placebo group, the experiment indicates that the treatment has value.
Clinical Trials Explained
A Potential Problem With Placebos
Clinical trials must be performed before health agencies give permission for a treatment to be prescribed for the general public. Animal tests and tests on isolated human cells are generally performed first to demonstrate the likely effectiveness and safety of the test substance. These tests aren't enough for the regulatory agencies, however. The agencies want to see the results of well-designed clinical trials.
Using a placebo group in a clinical trial is good for demonstrating the effectiveness of a treatment, but it may not be good for the people within the group. If the disease experienced by the subjects is progressive and the test treatment is helpful, those people given the placebo may be at a disadvantage.
The results of the proinsulin peptide experiment are wonderful for the people given the peptide, since their beta cell destruction was halted. The results aren't good for the people who were given the saline solution, since their beta cell destruction continued.
If a researcher decides to use a placebo in a clinical trial, the people who volunteer for the trial know that they may be given the placebo instead of the test treatment. In addition, the researchers don't know for certain whether the test treatment will be effective in humans or exactly how it will affect the body, so there might be a disadvantage to receiving it. Nevertheless, some people consider the use of placebos in certain types of trials to be unethical because the placebo group misses any chance for their disease to be treated.
The Future for People With Type 1 Diabetes
The peptide research could be very useful for diabetics who still have a significant number of beta cells left. Unfortunately, it may not be applicable to patients who are in this situation today. The researchers think that the new treatment will be ready for general use in five to ten years. In many countries, there are a lot of steps that must be performed before a new medication is approved. Understanding how to reset the immune system in an autoimmune disease could prove to be very important, however.
Stem cell research offers hope for people who have had type 1 diabetes for a long time. Stem cells are unspecialized cells. They have the wonderful ability to produce specific specialized cells under the right conditions. Researchers have been able to produce pancreatic beta cells from stem cells in the lab. It's hoped that eventually it will be possible to produce a large number of beta cells for transplantation into diabetics. Another area of research that could be helpful is the transplant of beta cells from a donor's pancreas into the pancreas of a person with diabetes.
If either of the processes described above happen, it will be important to stop the patient's immune system from attacking the transplanted cells. The results of the peptide research could be very helpful in this respect.
- Baxter, Rachel. "Type 1 diabetes may be halted by experimental immunotherapy." New Scientist. https://www.newscientist.com/article/2143414-type-1-diabetes-may-be-halted-by-experimental-immunotherapy/ (accessed August 9, 2017).
- "Pioneering immunotherapy shows promise in type 1 diabetes." Medicalxpress. https://medicalxpress.com/news/2017-08-immunotherapy-diabetes.html (accessed August 10, 2017).
- Ali, Mohammad Alhadj et al. "Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes." Science Translational Medicine. http://stm.sciencemag.org/content/9/402/eaaf7779 (accessed August 10, 2017).
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© 2017 Linda Crampton