COPENHAGEN, Denmark — Doctors may need to rethink everything they know about insulin and diabetes, a new study explains. Researchers in Denmark say it’s likely that a large portion of a diabetic’s insulin dose doesn’t work the way it should. Using highly advanced single molecule microscopy, a team at the University of Copenhagen is revealing for the first time that Type 1 diabetes patients may be taking medication that doesn’t absorb into the human body as fast as scientists have thought for years. This could be affecting millions of diabetics worldwide, the team warns.
Study authors explain that insulin is a hormone produced in the pancreas which regulates the amount of sugar in the blood. People with diabetes have immune systems which attack and destroy the organ’s insulin-producing cells. Many Type 1 diabetes patients know there are differences in how long and how rapidly various insulin dosages work within their bodies. Getting too much or too little can lead to dangerous health complications.
‘It is now apparent to us that we’ve gotten things wrong by 200 percent.’
The absorption of insulin depends on how insulin molecules assemble themselves into clusters. While a single molecule provides patients with rapid relief, clusters of six molecules (hexamers) provide more long-lasting help. For decades, the team says that scientists believed insulin assembles with a certain distribution of one, two, and six-molecule clusters. Pharmaceutical companies have been designing insulin doses based on the assumption that many of these clusters consist of single molecules. The new study finds that this assessment was very wrong.
“It is now apparent to us that we’ve gotten things wrong by 200 percent. There are only half as many single molecules in insulin compared to what we thought. Conversely, there are far more six-molecule clusters than we assumed. These experiments were not on animals but were performed on a microscope slide and one should be careful how to interpret their direct application to humans,” says lead study author Professor Nikos Hatzakis from Copenhagen’s Department of Chemistry in a university release.
“However, our results may mean that when we believe to be administering a certain dose, it may mean that insulin behaves in a different way than expected and that even better insulin therapeutics can be developed.”
Will this harm Type 1 diabetes patients?
Simply put, the study finds current insulin doses may not be absorbing into the bodies of diabetics as expected. While this isn’t necessarily a life-threatening problem for patients, the findings provide scientists with an opportunity to create new medications that precisely address a diabetic’s needs.
“Insulin preparations have only gotten better and better over the years, and a great many diabetics are well regulated. However, the development of insulin preparations has been based on a certain assumption about how the molecules assemble. With the crude standard model, this process was never been appreciated at a detailed level. That’s what we can do,” says co-lead author Professor Knud Jensen.
“This doesn’t mean that current insulin medications are bad or that patients have been medicated wrongly. But we now have a basic understanding of how insulin behaves and how much could be available to the body as rapid-acting medication. We now have the right method for providing us with accurate figures. We hope that the industry will use this or a similar tool – both to check current insulin preparations and to develop new ones,” adds Hatzakis.
The team used a mix of chemistry, machine learning, computer simulations, and advanced microscopy to make this discovery. Overall, they looked at roughly 50,000 clusters.
“The clustering of insulin is incredibly important for how preparations work. Because the difference between a rapid- and slow-acting insulin preparation is dependent upon how quickly the molecules assemble in clusters and how quickly they disassemble. Access to highly advanced equipment makes it relatively simple and fast to gain insight into exact concentrations, knowledge that at the same time, is also quite sophisticated,” says lead author Freja Bohr, a Ph.D. fellow in Nikos Hatzakis’ research group at the Department of Chemistry.
40 million children and adults take daily doses of insulin
The study authors also found that the molecular clusters can either grow or shrink “at far more different intervals than previously supposed.”
“Without being able to say exactly how just yet, this should make it possible to expand the number of ways in which preparations are designed. This could lead to an insulin with a different effect profile that reduces the fluctuations in patients’ blood sugar – which remains a major challenge,” says Bohr.
“I sometimes receive inquiries from parents who ask if there is something better for treating their young children. When a person has poorly regulated Type 1 diabetes, they can feel awful for long periods of time. Among other things, they can wake up with nightmares, feel unwell due to low or high blood sugar concentrations, risk losing consciousness due to low blood sugar and suffer consequential damage to their eyes and feet later on in life. So, if life can be made better for children by making better insulin, that’s fantastic!” Jensen concludes.
The study is published in the journal Communications Biology.