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Researchers in Trondheim are developing a new drug for diabetics who must take daily insulin injections. The key is a hormone that relaxes the smallest blood vessels inside.
Norwegians lead in terms of the number of new cases of type 1 diabetes among children, young people and adults each year. This disease is caused when the pancreas does not produce enough insulin. There is no cure and patients must take insulin for the rest of their lives.
The Artificial Pancreas Trondheim (APT) research group has filed a patent for a new solution called MicroGlucagon. It can help people with type 1 diabetes tackle major challenges by reducing the rise in blood sugar levels after meals and better controlling blood sugar levels.
Insulin is required to lower blood sugar levels. Diabetics have a deficiency of this hormone because their pancreas has stopped making it. Therefore, the patient himself needs to take the exact dose at the right time, that is, several times a day.
This requires a fine balance. Too much or too little insulin can have fatal consequences.
In a new approach developed by researchers at the Norwegian University of Science and Technology (NTNU) and St. Olav's Hospital, small amounts of glucagon were added to a regular fast-acting insulin mixture. Glucagon is a hormone that significantly increases blood flow in the exact area of the dermis where insulin is administered. This solution provides the body with additional impetus to quickly absorb insulin that patients take with meals.
Microglucagon was found to be more effective and faster acting than the best and most effective fast-acting insulin preparations for dietary use currently on the market. ”
Professor Emeritus Sven Magnus Carlsen
Carlsen has led the APT Interdisciplinary Research Group since its inception in 2013, based at NTNU and St. Olav's Hospital.
Carlsen is an endocrinologist, an expert in the organs that produce hormones and the diseases that occur in those organs.
Studies conducted by researchers on pigs under general anesthesia showed that insulin spiked with trace amounts of glucagon reached full effect up to 10 minutes faster than the fastest currently available insulin. Additionally, using a microglucagon mixture appears to increase the amount of insulin absorbed by the body, perhaps by as much as 30 percent.
“But most importantly, the faster insulin is absorbed, the faster it is cleared from the body,” Carlsen says.
The researchers believe their solution may reduce the risk of hypoglycemia for up to 3 to 5 hours after meals. Postprandial hypoglycemia may be a problem for some patients.
Microglucagon can be used by all patients who self-inject insulin daily. It can also be used in insulin pumps and semi-automatic artificial pancreas systems.
These are so-called hybrid solutions and are already commercially available.
If researchers are successful in bringing this solution to market, it would pave the way to significantly improve blood sugar control for all type 1 diabetics, regardless of type of insulin treatment.
Much research and documentation remains. But researchers are already finding that the MicroGlucagon solution is helping them achieve their goals.
“We believe that using MicroGlucagon will significantly improve current semi-automated solutions, and we also believe that it will help in the development of new artificial fully automated pancreatic systems,” Carlsen says.
The goal is a fully automatic, closed system that constantly measures blood sugar levels. This system constantly calculates the amount of insulin your body needs and ensures that the correct dose is continuously administered.
This means patients do not need to constantly monitor their blood sugar levels throughout the day.
Insulin intake is essential for people with type 1 diabetes, but another hormone, glucagon, is playing a leading role in the APT Group's latest research. This hormone is also produced in the pancreas, but whereas insulin lowers blood sugar levels, glucagon works to raise them.
In this way, the two hormones help maintain balanced blood sugar levels in healthy people.
Glucagon has one very special property that researchers have discovered and exploited. In technical terms, this hormone causes vasodilation. This means relaxing the smooth muscles lining the smallest blood vessels. As a result, blood vessels dilate and local blood flow increases significantly.
“What we've done so far, and what could be a big advance, is we've added trace amounts of glucagon to our fast-acting insulin solutions. “We have researched insulin solutions. The important thing is that we can improve on the current best options,” says Sven Magnus Carlsen.
Glucagon raises blood sugar levels, but the new microdoses are so small that they don't affect the liver's release of glucose. Therefore, the risk of side effects is not an issue.
Additionally, adding glucagon costs little.
“We're talking about 5 nanograms per unit of insulin, which means the solution contains 1 glucagon molecule for every 420 insulin molecules. The dosage is so small that the cost is negligible.” says Carlsen.
He calculated that the additional annual cost of glucagon in Norway would be approximately NOK 100 for a patient taking an average of 60 units of insulin per day.
In total, it is estimated that approximately 500 million people worldwide have diabetes. About 9 million of them had type 1 diabetes in 2017, according to the World Health Organization's latest statistics.
Approximately 26,000 Norwegians are currently living with the disease, and more than 400 young people under the age of 18 are diagnosed with type 1 diabetes each year in Norway. According to the Norwegian Institute of Public Health, the number of new infections in this group has doubled every year since the 1970s.
While type 1 diabetes cannot be prevented or avoided, type 2 diabetes is largely preventable through a healthy and active lifestyle.
The artificial pancreas Trondheim is funded by the Norwegian Research Council and is also working on several other projects under the auspices of the Norwegian Center for Digital Life. These include DIAP (Double Intraperitoneal Artificial Pancreas) and listening to the patient's voice.
Researchers now need to document that the MicroGlucagon solution is stable and works equally well in humans. Professor Sven Magnus Carlsen and his colleagues are preparing a major clinical trial in his type 1 diabetic patients in the spring of 2024.
Carlsen is cautious in estimating how long it will take for microglucagon to reach the market. Just documenting that the solution is fully stable can take several years and require the involvement of pharmaceutical companies.
“So it might take three to four years at most, but that's only if everything that needs to be done goes perfectly smoothly,” Carlsen said, adding that three to four years is actually a very long time. He added that it was short. medical research.
“Developing new medicines is a long-term competition. We need to understand market and industry needs while also challenging existing solutions,” says Hilde Kjeldstad Berg from NTNU Technology Transfer.
Mr. Berg helped researchers obtain patents and develop businesses. The goal is to license the solution to established industry players during 2024.
“We have to work with the world's leading companies in this market. NTNU and St. Olav's Hospital can only take this kind of development to a certain level. Then the industry has to take over. ” she says.
Berg said it takes an average of 10 to 15 years for a new drug to come to market. She still believes she can get results faster with microglucagon because it is a natural hormone with little risk of side effects.
Type 1 diabetes is a complex and difficult disease that cannot be prevented or treated. Affected people must self-medicate with insulin for the rest of their lives.
“Thousands of patients walk around every day, using small computers to administer their own medicines that, in the worst case scenario, can actually kill them if they don't take them or take too much.” “The number of patients and the extent to which they treat themselves, advances in technology mean that type 1 diabetes is the most technologically advanced disease in the world,'' says hormone expert Sven Magnus.・Carlsen says.
Insulin needs to work as quickly and efficiently as possible, and the time it takes is the biggest challenge. All people with type 1 diabetes must take fast-acting insulin with meals.
But even the fastest-acting insulins on the market take an hour and a half to take full effect. That is, the patient must necessarily take insulin 15-20 minutes before meals.
“Everyone with diabetes forgets to take their insulin from time to time, and even when they do remember, they may delay eating. Of course, many people don't always know what or how much to eat. Some people wait until it's over, and then they have to eat to get their insulin, but that's obviously too late to get good blood sugar control,” Carlsen says.
So it would be a major advance if we could develop an insulin solution that would have the same effect on blood sugar levels whether taken with a meal or 15 minutes before a meal.
“The quantum leap will only occur if a fully automatic artificial pancreas is created that provides adequate blood sugar management. We are actively working on this problem,” says Sven Magnus Carlsen. .
Insulin was first administered 101 years ago to a 14-year-old boy in Canada. In the early stages of insulin, the hormone was produced from pig pancreases, and it took about 70 pig pancreases to treat one diabetic patient for his entire year.
Currently, this hormone is artificially produced and has little to do with pigs, but it is important in animal studies conducted by researchers at NTNU and St. Olav's Hospital.