This November, we celebrate 100 years since the discovery of insulin, the hormone that provides the key to understanding and treating diabetes. In this Special Feature and podcast, we look at how far insulin research has come, and we consider what its future may hold.
Insulin is the hormone that helps regulate blood sugar levels, keeping them at healthy concentrations. The pancreas is the organ that produces this hormone, which is normally released in quantities dependent on the levels of blood sugar present in the system at any one time.
People whose bodies are unable to regulate blood sugar levels have diabetes mellitus, which can be of two types, depending on why this regulation does not occur.
In type 1 diabetes, the body does not produce insulin, while in type 2 diabetes, it does not respond to the insulin produced and released by the pancreas.
Around the world, hundreds of millions of people live with a form of this chronic condition, and insulin treatments are key to its management, particularly to the extent that type 1 diabetes is concerned.
People with type 1 diabetes must take insulin, as their bodies do not produce it. Individuals with type 2 diabetes control their blood sugar levels typically through special medication and dietary and lifestyle interventions.
However, some may also require insulin treatment if the cells that produce insulin — called pancreatic beta cells — deteriorate in time and stop producing sufficient insulin.
In this Special Feature and associated “In Conversation” podcast, we offer an overview of the importance of insulin, its history, and what future research likely holds for insulin therapy and the management of diabetes.
To find out more about the impact of type 1 diabetes and the challenges of using insulin, we spoke to Virginie, a woman who received a diagnosis for this condition in her 30s.
For insights into current insulin research and potential future developments, we interviewed Dr. Thomas Barber, honorary consultant endocrinologist and assistant professor at the Warwick Medical School in the United Kingdom.
Diabetes was known — as a collection of symptoms — over 3,500 years ago, as a papyrus dating from 1550 before the common era (BCE) was already describing a condition consistent with the symptoms of diabetes.
Even though physicians have encountered and treated diabetes throughout history, researchers only discovered the reason behind it around 100 years ago: insulin, the hormone that regulates blood sugar levels.
In 1889, Joseph von Mering and Oskar Minkowski, two researchers at the University of Strasbourg in France, removed the pancreases of dogs and found that the animals would then go on to develop diabetes.
As we now know, the pancreas is the organ that produces insulin. However, von Mering and Minkowski were not able to establish this connection at the time.
It was a little over 30 years later, in 1921, that Sir Frederick Banting and Charles Best — working in the laboratory of John Macleod — from the University of Toronto in Canada extracted insulin from the hormone-producing cells found in the pancreases of healthy dogs.
They then injected dogs with diabetes with this “extract” and thereby made the discovery that changed the face of type 1 diabetes treatment forever.
In 1922, Banting and Best treated a young boy with type 1 diabetes by injecting him with insulin. This saved his life — at the time, type 1 diabetes became a terminal illness more often than not — and cemented the importance of the researchers’ discovery.
Banting and Macleod won the Nobel prize in medicine “for the discovery of insulin” in 1923.
In 1946, researchers discovered intermediate-acting insulin, also known as Neutral Protamine Hagedorn (NPH) insulin, which persists in the body for 14–24 hours, which means that people who take it require fewer injections. This is still one of the most widely used types of insulin to this day.
At present, however, NPH insulin is no longer extracted from animal sources. Instead, researchers synthesize artificial human NPH insulin in the lab.
At present, there are several different types of therapeutic insulin, and people may have taken one or several of these, depending on their individual needs.
These types are:
Depending on their needs and what is accessible to them, people may receive therapeutic insulin through:
While the subcutaneous delivery of insulin may make it harder for some people to adhere to the correct treatment regimen, other delivery methods have so far proved unsuccessful.
For example, in the 1990s, some companies have also developed and attempted to commercialize insulin inhalers, which would deliver the hormone in aerosolized form.
However, these never took off, most likely because they are less effective than delivering insulin subcutaneously, as some of the insulin gets lost in the process.
So what does the future hold for insulin research and therapy? In some ways, we could say, the future is now, as people are already using smartphone technology to assist them in adhering to their treatments and determining how much insulin they need to use.
Today, individuals use mHealth technology — referring to the practice of healthcare supported by mobile smart devices — to help them monitor their blood sugar levels, so they know how much insulin to take. Glucose monitors are currently available — these are small sensors placed under the skin that pick up on variations in blood sugar levels.
These connect to a smart device and allow the person to read their blood sugar levels at any time and share them with a doctor in real-time.
Some fully automated insulin delivery systems are also available. These are called “closed-loop insulin systems,” also known as “artificial pancreases.” They work by transmitting real-time blood sugar level data to a smart device that then communicates with a person’s insulin pump, regulating how much insulin enters the system at any one time.
However, some challenges remain that future developments need to address. These include insufficiently accurate glucose monitoring devices, as well as concerns regarding user data collection. Current closed-loop systems also rely on user control, while researchers are yet to develop fully independently running artificial pancreases.
Dr. Barber noted that independently functioning artificial pancreases are akin to the “Holy Grail” of diabetes therapy.
“There is some fascinating research to suggest that [the independent artificial pancreas] can be done,” Dr. Barber told us.
“It’s been shown that can actually reduce hypoglycemic rates by having that kind of technology in place. But we’re some way away from actually being able to have an artificial pancreas, which doesn’t rely on the patient at all. And really, […] I think it will come, but we’re not quite there yet.”
– Dr. Thomas Barber
Another pathway for future research is gene therapy that would trigger the expression of insulin-producing cells, thereby tackling the cause of type 1 diabetes at the root. The research so far, while it has garnered some interest, has been in animal models, and scientists are yet to take this to the next step: clinical trials in humans.
Finally, scientists are also looking at ways of developing better insulin, and several areas of investigation appear to hold promise.
One option is developing glucose-responsive or “smart” insulin. One of the main challenges in treating type 1 diabetes and severe type 2 diabetes remains administering insulin doses that accurately “match” blood sugar levels.
If blood sugar levels become or remain too high, a person can experience hyperglycemia. This, in turn, can lead to various complications in the long term, such as eye problems or diabetic ketoacidosis.
Yet if a person takes too much insulin, they can develop hypoglycemia, where their blood sugar levels are too low. Its symptoms can include heart palpitations, dizziness, and blurred vision. It can also lead to further complications, such as seizures and loss of consciousness.
Smart insulin would help address the risk of hyperglycemia and hypoglycemia by responding to changes in a person’s blood sugar levels in a way that would mimic healthy insulin function.
Eliminating or attenuating insulin fibrillation and aggregation — a process that renders insulin manufacturing more difficult — would make it easier to produce and store insulin.
Another area of development looks at ultrarapid insulin, which starts acting sooner after delivery. It helps improve the management of fast changes in blood sugar from before to after a meal — a process known as “postprandial glucose excursions.”
Another issue that needs addressing in the near future is the lack of accurate and consistent information regarding both insulin therapy and the unexpected factors that can influence a person’s blood sugar levels, besides diet.
Virginie, for instance, wondered how much researchers and clinicians know about the relationship between anxiety and blood sugar levels and how this might affect people with diabetes who require insulin therapy.
In answer to her question, Dr. Barber explained that “glucose control is far more complex than simply what [a person’s] levels of insulin are, and indeed how much insulin you inject.”
“There’s actually 101 things [that] can influence blood sugar levels. And in fact, one of those is mental and emotional status at the time. And if you’re worried, or stressed, or anxious, that in itself can actually push your blood sugar levels up, because it’s associated with the release of the stress hormone cortisol and also the sympathetic response as well, which is the fight or flight adrenaline release, both of which act to raise your blood sugar levels.”
– Dr. Thomas Barber
This is one of the many reasons why it is so important for doctors to listen closely to the experiences of people living with diabetes.
“[W]hen I’m seeing patients in clinic, I’m acutely aware of the fact that they have far more insight into their own diabetes than I do,” Dr. Barber noted. “They’ve been living with this [condition] day after day, hour after hour, week, months, years, sometimes even decades. And I think it’s really important that as healthcare professionals, we’re aware of this and we respect that.”
Virginie further noted that anxiety regarding insulin treatments can also affect those living with diabetes in another way. Often, those around her are anxious about how the condition affects her and whether she has been able to take the correct insulin dose at the correct time.
Diabetes can also take a heavy toll on the friends and families of those with this condition, she pointed out.
Dr. Barber acknowledged the real human impact of a diabetes diagnosis and the serious lifestyle adjustments that come with having to undergo insulin therapy.
One of these is the necessity of self-injecting insulin, which, he said, causes anxiety in many patients. “And understandably, because of all of these factors, there’s often quite a lot of resistance to the idea of going on to [insulin] therapy,” he admitted.
The solution? Empathetic sensitive, and mental health-aware care, according to Dr. Barber:
“There is a relative lack of proper psychology and talking-based therapies for patients with diabetes, and one almost feels as if there’s a need for these patients not just to have the standard education on diabetes, but to have the focused psychological support, which is really a separate thing from education. I think they should have, obviously, the two together, but the psychological support is often lacking. And I think that really is an unmet need. And I think it’s something we could certainly do a lot more on in the future.”
Perhaps the greatest challenge going forward, however, is ensuring equitable access to appropriate care and education for the management of diabetes.
While this condition is common worldwide, it does not affect everyone in the same way, and not everyone has timely access to diagnosis and care.
Black, Hispanic, and American Indian individuals have a higher likelihood of developing diabetes compared with people of other races and ethnicities.
Yet, people from these groups face the highest rate of disparities in access to appropriate healthcare, often due to systemic racism and socioeconomic factors.
To this day, Dr. Barber told us, lack of access to insulin remains the number one cause of death among children with type 1 diabetes worldwide:
“Did you know that globally, the most common cause of death for a child living with type 1 diabetes is actually [the] lack of access to insulin? That’s an incredible fact. It’s a tragic fact. And it’s actually quite shameful that after 100 years of having insulin, [which the World Health Organization (WHO) classes] as an essential medication, that children around the world with type 1 diabetes are dying because they don’t have access to this therapy. Something needs to be done.”
However, solving the issue of inequitable access to insulin therapy, glucose monitoring systems, and even basic education about diabetes is going to be no mean feat, according to Dr. Barber.
“[I]t’s a hugely complex issue,” he pointed out. “It’s not just the case of providing insulin, […] there [are the] huge complexities of […] infrastructure, data collection, [taking] cultural differences [into account] and so on.”
Some initiatives do exist to address these disparities. One example is the 100 Campaign, “which is aiming to improve the situation for patients around the world to have access to insulin,” Dr. Barber told us. However, we are still a long way away from solving this problem.
Virginie emphatically expressed a hope that going forward, healthcare decision-makers will work to improve access to care, health education, and diagnosis for people living with diabetes.
“I think it’s very important that […] we make sure we provide the access for all […] not just […] to insulin, but access to the diagnosis, and to actually think about our own assumptions [about diabetes],” she told us.
“Certainly, I didn’t know that thrush could be a symptom of diabetes. I also had a foot drop, which I didn’t know could be a symptom. I was thirsty all the time. [Before my diagnosis,] I was drinking more than 6 liters [of liquid] per day and only stopping because I knew 6 liters — that’s a lot. […] So my hope is that […] any sort of worry and concern is taken seriously. […] It has taken a while for me to get the diagnosis, and we’re only talking months. So I’m thinking about people who have to wait for years for [a] diagnosis. And I think it’s really important that […] we consider that as well.”