The purpose of the so-called ‘artificial pancreas’ should be to imitate a healthy pancreas. Aaron Kowalski reports on the latest stand in the following DPJ interview. 

There have been vast developments in recent years in the treatment of type 1 diabetes in children and adolescents. Around 30 years ago, intensified insulin therapy was introduced. Since a decade now, insulin pump therapy has started to establish itself.

Pumps with Additional Uses
The latest pumps do not only simply administer insulin. They are able to, for example, automatically alter the basal rate as needed, and save the carbohydrate-to-insulin correction factors. Even small children are able to administer insulin themselves using the ‘bolus expert’. It has even become possible to transfer blood sugar readings from monitors to the pump. In combination with the glucose sensor, a system is created which measures blood sugar and transfers the values to the pump. You can enter the intended consumption of carbohydrate, and the pump will suggest the appropriate insulin dosage accordingly. In this way, the new-generation insulin pumps can regulate boluses to correct shortages of insulin almost as well as the body of a person without diabetes.

To really replace the functionality of a normal pancreas, however, this system not only should be able to register when the blood sugar levels are too high or too low, but also to administer the proper insulin dosage automatically.

What would Happen If ...
How would it be if the pump could automatically stop when the blood sugar is too low, or automatically administer extra insulin when the levels are too high? If this were the case, we would be a step closer to fully replacing the functionality of a real pancreas. An artificial pancreas? How far, in actual fact, are we from this?

Dr Aaron Kowalski, himself having had type 1 diabetes since childhood, is Strategic Director of the Juvenile Diabetes Research Foundation (JDRF). He also leads the organization responsible for the ‘Artificial Pancreas’ project. He lives with his family in New Jersey, USA. His aim is to improve therapy for type 1 diabetes, through the support of the JDRF.

We met him at the Karl-Stolte Seminar in Hannover. In this interview, he reports enthusiastically about his project, his goals, and his dreams.  

 

DPJ: Dr Kowalski, what exactly is the ‘Juvenile Diabetes Research Foundation’? What is its mission?

Dr Kowalski: The JDRF is a charitable funder that aims to improve treatment for diabetes and its complications by supporting research in this field. The foundation was established in 1970 by parents of children with type 1 diabetes. It is a worldwide organization, offering many events in order to award research programmes with its funds. The JDRF’s main areas of research are:

1. autoimmunity
2. beta-cell replacement
3. beta-cell regeneration
4. metabolic control
5. complications

 

DPJ: You are Director of the ‘Artificial Pancreas’ project, whose aim it is to develop and implement an artificial pancreas...

Dr Kowalski: The ‘Artificial Pancreas’ project falls within the category ‘metabolic control’. It is centred around the fact that studies have proven that maintaining good blood sugar values is a considerable factor in the prevention of complications. Good blood sugar values can be achieved with lots of discipline. However, even in patients with good HbA1c values of, say, under 7%, studies using glucose sensors have shown that the blood sugar values can oscillate widely for several hours during the day. In view of this, the fact that the average HbA1c value in the USA lies at around 8%, shows that the oscillations are even more extreme. Our aim is to find out how to avoid such swings. In order to reach this goal, we need more sophisticated technology. A recent JDRF study on the influence of glucose sensors on the metabolic control of patients with type 1 diabetes showed that the wearing of a continuous glucose sensor improves the HbA1c values. To achieve this, however, long-term use is necessary. 

With our project, we intend to achieve more than just the improvement of metabolic control. I believe that the wearing of such a device improves quality of life. As you well know, diabetes accompanies the person day in, day out. Decisions must constantly be made as to the amount of insulin one needs, when and how much to eat (once more before bed, or not), when and how often to measure blood sugar, and so on. The artificial pancreatic system can serve to simplify all that.

 

DPJ: What exactly does an artificial pancreas involve?

Dr Kowalski: The artificial pancreas is not – contrary to what many people believe—a system that has to be implanted into the body. It is a system that is worn externally. The two main parts of the system already exist, namely, the insulin pump and the glucose sensor that measures the blood sugar levels in the tissue and transmits these results to the pump. The biggest challenge for us at the present time is to get these devices working efficiently together. Extremely complicated mathematical algorithms are necessary for this. After all, the safety of the user is at stake.

DPJ: How can the JDRF help in getting the artificial pancreas ready for the market?

Dr Kowalski: Our task is to support those with innovative ideas from the realm of basic research, and to assist those who undertake clinical studies which will enable the best possible treatment modalities for the patients. Also, the larger randomized studies on the effectiveness of the continuous blood glucose monitoring system are of great significance to us. The results of these studies are also a key factor in the subsequent possibility for reimbursement by the medical insurance companies. Only if the effectiveness of these technologies is proven will the users be financed.

 

DPJ: When do you think such a system will be available?

Dr Kowalski: The advancement of this system focuses, in the most part, on the further development of the hardware and their algorithms. I think that, in five years, a completely closed system (closed loop) comprising all the parts will be available on the market. This process is most likely to take the form of a kind of evolution involving all the conventional devices that will gradually offer more and more possibilities over a period of time. The steps will probably be as follows:

1. Automatic STOP function
The next step will be the development of a STOP function, whereby the insulin pump will automatically stop insulin administration for a period of two hours as soon as a specific glucose value is exceeded. This will serve to prevent severe hypoglycaemia. This is, in fact, already possible in some devices.

2. Reduction of hypoglycaemia (‘hypo minimizer’)
The next possible advancement would be an alarm signal that will sound when the device predicts hypoglycaemia. If the user doesn’t react, the pump will reduce the insulin administration accordingly.

3. Reduction of hypo- and hyperglycaemia (‘hypo and hyper minimizer’)
This function would act in exactly the same way as the ‘hypo minimizer’, but with the addition of an alarm system for situations when the blood sugar levels begin to rise – in which case the device would automatically administer a higher insulin dosage.

4. Mixed system (‘hybrid closed loop’)
The pump can, with the assistance of a certain algorithm, calculate the required dosage for boluses.

5. Complete system (‘closed loop’)
The exact insulin requirement will be calculated by the pump using an algorithm. The insulin would then be administered accordingly, so that the user would be automatically set on the optimal glucose levels. 

6. Multi-hormone, fully automated closed system with insulin and glucagon
With the addition of a second hormone (e.g., glucagon, an insulin antagonist), the metabolic control of the user will become more and more like that of a person without diabetes. 

 

DPJ: What, in your opinion, are the biggest hurdles to attaining a closed system?

Dr Kowalski: As already mentioned, the safety of the patient is of highest priority. Only in the context of studies, or under close clinical supervision, is the use of a closed system possible today. The system, however, must work reliably around the clock. What would happen, for instance, if the sensor made a false reading and the wrong insulin dose was given? In order to avoid such cases, it may be necessary for the user to wear more than one sensor.

 

DPJ: For whom is the artificial pancreas most suited? Are there people with type 1 diabetes for whom this system is not suited?

Dr Kowalski: Certainly the artificial pancreas is not suitable for everyone, just as pump therapy is not suitable for everyone. Not all people like to wear devices on the body – especially if the user has to wear one or more sensors in addition to a pump.

 

DPJ: Dr Kowalski, we thank you for this discussion

 

Action Speaks Louder than Words ...
In fact, Dr Kowalski didn’t have to express his opinions on the development of insulin pump and glucose sensor technology at all! On being served a large schnitzel during our interview, he glanced at the reading on the glucose sensor he pulled out of his pocket and, in the next instant, was pressing a couple of keys on the insulin pump he wore on the other side.  

More on JDRF
For more information on the Juvenile Diabetes Research Foundation, see www.jdrf.org; the ‘Artificial Pancreas’ project can be found in the ‘Life with Diabetes’ section.

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Interview: Drs Nicolin Datz and Thorben Kracht, Hannover