In December 1921, a 14-year-old boy named Leonard Thompson was brought to Toronto General Hospital in Canada. He was diagnosed with type 1 diabetes, a disease in which the hormone insulin is no longer produced by the body. Leonard was on death row due to the lack of insulin, which is important for controlling glucose levels in the body and providing cells with energy. In 1921,
Leonard was chosen to receive a promising new treatment: a purified extract of the pancreas of an ox containing a protein that was later called insulin. Toronto scientists had tested the extract on dogs with diabetes and found it was able to lower glucose levels and keep the dogs alive. On January 11, 1922, Leonard was the first patient to be injected with the extract and it worked, lowering his glucose levels. This was a historic moment as it marked the discovery of insulin and the treatment of type 1 diabetes.
Insulin is a crucial hormone that controls the uptake of glucose by the cells of the body, providing energy and regulating glucose levels in the blood. Even if you eat a large amount of sugar in a short period of time, insulin prevents the glucose levels from rising too high. It also preserves muscle and healthy fat tissue in the body. In Leonard's case, he had type 1 diabetes, a condition in which the insulin-producing cells in the pancreas, called the islets of Langerhans, were destroyed by the body's own immune system. This leads to a lack of insulin production and in turn, causes the body to break down muscle and fat tissue. Leonard's parents were desperately awaiting a medical breakthrough in 1921, as there was no way to reconstruct the destroyed insulin-producing cells.
Imagine the relief and hope Leonard's parents must have felt when he was selected to receive a promising new treatment for his type 1 diabetes. The treatment was a purified extract of the pancreas of an ox, which contained a protein later named insulin. Toronto scientists had previously tested the extract on dogs with diabetes and found that it was able to lower glucose levels and keep the dogs alive. Leonard Thompson was the first human patient to receive the treatment on January 11, 1922 under the supervision of his Toronto doctor, Walter Campbell.
Several injections followed during that month, and the extract proved to be effective in lowering Leonard's glucose levels. It is difficult to imagine the thoughts of the doctor as he administered these life-saving injections for the first time to a young boy with type 1 diabetes. He must have been aware that this was a historic moment, not only for Leonard, but also for the treatment of other people with type 1 diabetes. This was the discovery of insulin.
That would soon follow was held on the front pages of newspapers. Toronto doctors on track of diabetes cure, but was it a cure? What will people with Taiwan diabetes say now that more than 100 Years of insulin treatment have passed? They will say that having type 1 diabetes is hard work. That insulin must still be administered several times a day, every day for the rest of their lives. They will say that glucose values need to be measured by finger Pricks or glucose answers every day for the rest of their lives.
They will say that almost all relevant daily activities have an effect on glucose levels, so they need to continuously think about glucose control and the right amount of insulin. They will say they can never take a break from their diabetes. That there is this continuous threat that glucose levels become too low due to excess insulin leading to loss of consciousness. That there is an increased risk of complications with damage to eyes, kidneys, and nerves, because with insulin treatment, glucose levels are still not optimal. People with type 1 diabetes will say that sometimes these potential consequences paid a bleak.
Type 1 Diabetes Research Progress
Picture of their lives in the back of their mind; they will say that one does not have diabetes alone. Also, parents, partners, loved ones feel the impact of the disease and experience the disease burden. Insulin treatment is no cure. Doctors, together with diabetes specialist nurses, nutritionists, and medical psychologists, can offer support and guidance so that people with type 1 diabetes can self-manage their disease at home. We can provide preventive treatment to reduce the risk of complications.
We can give positive feedback and participate in person-centered care. But do we offer a real solution in clinical practice? If we ask our patients, their answer would be no. Because a real solution to someone with type 1 diabetes means no more diabetes. What would a real solution look like? Well, the basic problem in type 1 diabetes is that the insulin-producing cells are destroyed, so new cells that completely take over glucose control are needed. Let's imagine someone with type 1.
Meet Jane, a 35-year-old woman who has been living with diabetes and taking insulin for most of her life. One day, Jane hears about a new treatment for diabetes on the news and attends her doctor's office to find out what the possibilities are for her. Her doctor writes out a prescription for one million islets and makes an appointment at the hospital so that the islets can be infused into her body. With this treatment, Jane can stop taking insulin injections and remove her glucose measurement device. Her brain can relax as she no longer has to worry about the daily efforts of self-management, losing consciousness due to low glucose levels, or long-term complications. Is this cell replacement utopia or is it clinical reality? On a small scale, this is what we already do. It's called islet transplantation.
In a special laboratory, we can isolate the islets of Langerhans from the pancreas of deceased organ donors and infuse these donor islets into the liver of a person with type 1 diabetes. The liver provides a new home for the insulin-producing cells to function. Every year at the Leiden University Medical Center, we perform islet transplantation to help people like Jane live a life free from the daily burden of diabetes management.
Center and has a limited number of centers around the world. Islet transplantations are carried out in a small number of people with complicated type 1 diabetes. Fantastic, isn't it? So, why do doctors not write out more prescriptions for these donor islets?
Well, several reasons. First, availability, there is a shortage of deceased organ donors, tens of thousands of organ donors will never be enough for the millions of people with type 1 diabetes. Second, rejection, your immune system will fiercely defend your body against cells that are not your own, so your immune system needs to be suppressed with medication leading to an increased risk of infections and other illnesses. But Island transplantation in type 1 diabetes.
Works, however, only few patients are eligible. So, how do we go from clinical reality for some to clinical reality for many? The answer is stem cells, human pluripotent stem cells to be precise. These types of cells have the capacity to turn into every cell of your body. In 1998, it was shown that special human stem cells could be cultured and expanded indefinitely, creating an unlimited source of these cells.
After many years, scientists were finally able to generate insulin-producing cells from these stem cells by mimicking the development of a pancreas in a tissue culture dish. This process takes about 30 days in Laboratories. 30 days to turn naive pluripotent stem cells into clusters of cells that can lower glucose. A novel stem cell islet archipelago that stretches beyond the reach of the eye. But can they also be used for treating people with type 1 diabetes in 2021?
The first scientific report showed that these cells can survive and secrete insulin for more than a year after transplantation in people with type 1 diabetes. Other data indicate that stem cell islets can lower glucose even to the extent that insulin is not necessary anymore. Does this mean we can repeat the headlines of 1922? Are we on track of a diabetes cure this time around, not for a few but potentially for all people who have diabetes? In my view, yes we are on track but we are not there yet.
The current stem cell islets are not recognized by our own immune system, so those drugs that suppress the immune system are still necessary.
Scientists are working on this problem, we have tools to make changes in these cells so that they may not be destroyed by the immune system. We may hide the cells in biomaterial scaffolds, kind of like a camouflage, so the immune system will not recognize them. It is an exciting time for diabetes research and we hope that soon we will have a real solution for all people with type 1 diabetes.
We can transform a patient's own cells into pluripotent stem cells and create custom stem cell eyelids. Despite these advancements, our main focus is reducing complications during the transplantation process and preventing the formation of tumor cells.
Despite the unknown risks, ongoing risk-benefit analysis is crucial. I am confident that researchers in academia and industry will eventually overcome these challenges, but it will take time. We are currently on an exciting journey in the field of islet replacement therapy for type 1 diabetes.
I understand the frustration of my patients who feel that progress is slow, but looking back, we have made significant progress in recent years. I am hopeful that one day, a patient like Jane, a 35-year-old woman with type 1 diabetes, will receive the news that her stem cell eyelids are ready for transplantation. Despite any challenges that may arise, scientists and healthcare providers are working towards a real solution and one day, people like Jane will be able to live a normal life without type 1 diabetes. The thought of this is truly sweet.
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