The realization that breakthroughs in biology-based therapies for diabetes are not imminent is spurring tech-based innovation in insulin delivery mechanisms
The days when ‘the only choice open to diabetes sufferers was that between death by coma and death by starvation’ passed unmourned into history in 1922, when insulin was first used therapeutically.
Even today, however, diabetes has lost none of its fearsomeness, because even today diabetics live in constant fear of overdosage or underdosage of their medicines, especially insulin, and of consequent hypoglycemic episodes and late complications that can result from inadequate treatment and prolonged elevation of blood glucose level.
Patients with diabetes whose blood glucose levels are kept close to normal by means of suitable therapeutic measures avoid the risk of dangerous hypoglycemic episodes and develop complications of diabetes considerably less frequently and later than their less successfully treated counterparts.
But there is realization that breakthroughs in biology-based therapies for diabetes are not imminent. Sure, there is hope that they’re going to happen, but more long-term research is needed.
In the meanwhile, technology that can meet this need is available and is spurring innovation in insulin delivery mechanisms. As a result, diabetes technology, and particularly the artificial pancreas, has become an area of very rapid academic and industrial development.
A precondition for this success is close monitoring of blood glucose levels. Therefore, a great deal of research activity has been directed towards the development of sensors that permit near-painless, continuous measurement of blood glucose level. The objective is to develop a system that pairs continuous blood glucose monitoring with an insulin pump and thus acts as an ‘artificial pancreas’.
Why Continuous Blood Glucose Monitoring Is Desirable
It is difficult to achieve good metabolic control in diabetics. Especially in patients on intensive insulin therapy, good metabolic control calls for frequent blood glucose determinations by patients themselves. The timing and dose of insulin injections have to be adapted to a variety of factors that influence blood glucose level, such as carbohydrate intake, physical exertion, sporting activities, stress (including operations, injuries and infections) and also rest periods such as periods spent asleep.
In addition to being painful and unpleasant, individual determinations of blood glucose by patients themselves using the conventional invasive techniques provide no more than a snapshot of the patient’s blood glucose level at the moment the blood sample was taken.
Continuous glucose monitoring (CGM), by contrast, would detect fluctuations in blood glucose level over a prolonged period and indicate when major deviations from the normal range occur. Every diabetic could benefit from continuous monitoring of their blood glucose level.
What Is An Artificial Pancreas?
An artificial pancreas is essentially a device that would both measure sugar levels and dispense appropriate amounts of insulin to keep blood sugar levels in optimal range. It would take much of the guesswork out of daily management of the disease and in the long-run, controlled sugar levels will help to lessen or avert the devastating complications from diabetes.
An artificial pancreas will integrate two currently available technologies ‒ continuous glucose monitors and insulin pumps ‒ with an algorithm that provides the right amount of insulin at the right time. It will enable people with diabetes to achieve tight blood glucose control avoiding both highs and dangerous lows, thereby significantly reducing the risk of the disease’s devastating complications.
Why Is An Artificial Pancreas Needed?
The current diabetes treatment market comprises three related but distinct submarkets that address different aspects of the condition. Products in the market are currently comprised of blood glucose monitors, lancets & test strips, continuous blood glucose monitors, insulin, insulin pumps, syringes, and other insulin delivery devices & anti-diabetic drugs. Right now, the most significant growth in the U.S. market is in continuous blood glucose meters, insulin pumps, and anti-diabetic drugs.
An artificial pancreas could potentially revolutionize diabetes care and management, significantly improving the ability of people with diabetes to maintain strict blood glucose control, and ‒ as a direct result ‒ helping reduce kidney disease, heart attacks and stroke, amputations, blindness, and death from severe hypoglycemia.
Extensive research shows that glucose control is the primary factor in avoiding the devastating complications of diabetes. The landmark Diabetes Control and Complications Trial (conducted 1983-1993) showed that intensive diabetes management and improved glycemic control reduces major long-term complications of diabetes.
A later study published in the New England Journal of Medicine found that intensive diabetes therapy aimed at achieving good control reduced the risk of any heart disease event by 42 percent, and the risk of nonfatal myocardial infarction, stroke, or death from heart disease by 57 percent.
However, clinical research shows that most people with diabetes are not controlling blood glucose levels nearly well enough. The risk of complications ‒ and the economic burden placed on our health care system ‒ could be significantly lowered with devices that improve blood glucose control. And good glucose control will probably enhance the effectiveness of promising new cure therapies such as beta cell regeneration and islet transplantation.
Diabetes Technology To The Rescue
There are several classes of technologies used for diabetes care at home. In general, the devices include monitoring of blood glucose levels and delivery of insulin. The monitoring can happen with finger sticks or with the newer generation of continuous glucose monitoring that permanently attach to the person.
Insulin delivery, the old-fashioned way, is through injections several times a day. The newer devices are insulin pumps. They attach to the person with little needles under the skin that deliver insulin at continuous rates.
But the current problem with even the most advanced treatment of diabetes is that these devices don’t talk to each other. Even the most sophisticated insulin pumps will keep delivering insulin regardless of the blood sugar level of the person because it doesn’t have any information coming from the monitors. That can cause severe reactions.
Boris Kovatchev, director of the Center for Diabetes Technology at the University of Virginia, has focused on diabetes technology for more than a decade.
His contribution to this area is to make these devices talk to each other in a smart fashion, to insert an algorithm that can take the reading from the monitoring device and tell the insulin pump to deliver insulin in a smart way.
The Artificial Pancreas Project is the most advanced application of the device. It connects the most advanced continuous monitoring device to the most advanced insulin pumps available in a continuous fashion — all the time. This is the top of the line integrated technology — and that means continuous monitoring of the person’s blood sugar levels and the reaction to changes.
The system’s “smart” algorithm, developed by Kovatchev’s team and collaborators from the University of Padova in Italy, uses existing continuous glucose monitoring and insulin pump technology to automatically regulate a patient’s insulin levels, with no action required on behalf of the user. The algorithm is currently being tested in clinical trials at the U-Va. Health System and 10 other centers spanning seven countries.
This project ‒ initiated by the Juvenile Diabetes Research Foundation (JDRF) ‒ has been going on since 2006. Kovatchev’s group was one of the first to join this project. Since then, it has grown significantly. Now, there are government initiatives in several countries and a lot of companies are interested in this technology.
The U-Va group has undertaken some extensive clinical trials on around 60 patients on that system for short periods of time for testing purposes. Besides, there are ongoing clinical trials in eight countries, all using Kovatchev’s patented technology or components of it.
The most challenging aspect of this technology is predicting the future. The reason that the future must be predicted accurately in this particular technology is that insulin delivery under the skin and glucose monitoring under the skin have delays.
“The monitoring of the blood sugar level generally works with a one-hour delay. Imagine you’re driving a car and you’re reacting to oncoming traffic with a one-minute delay. In situations like that, you have outdated data and delayed action. You have to anticipate what is going on in the next hour,” explains Kovatchev.
To make his device predict the near future for diabetes management, Kovatchev is developing a class of control strategies called model predictive control. Every human is assigned a mathematical model that mimics the functioning of the metabolic system of that person.
“Based on what that model says, we can predict the future. It’s similar to weather forecasts. But instead of weather models, we have models of a particular human,” he says with confidence.