What is the history of the development of 'artificial pancreas' that sheds light on the treatment of diabetes?

For diabetics who cannot produce insulin in their bodies, administration of insulin by injection and regular measurement of blood glucose level have been essential for survival. However, in recent years, artificial pancreass that automatically measure blood glucose levels and administer insulin have been put into practical use, and the lifestyles of diabetic patients are changing. Boris Kovachev , the central figure in the artificial pancreas development project, explains the history of such artificial pancreas.

A Smart Artificial Pancreas Could Conquer Diabetes --IEEE Spectrum
https://spectrum.ieee.org/artificial-pancreas-could-conquer-diabetes

People who do not have diabetes secrete insulin in the pancreas in response to fluctuations in blood sugar levels to keep them in the proper range. However, in the case of diabetics, the pancreas may not be able to produce insulin or the amount of insulin produced may be low, so it is necessary to supplement insulin by artificial means.

According to Kovachev, insulin was given to diabetics in 1922, and for decades, 'injection' was the primary method of insulin administration. Also, at that time, there was no way to measure blood sugar levels, so diabetics could only know 'whether or not blood sugar levels have reached dangerous levels' by detecting the sugar content in urine.

A portable blood glucose test kit was developed in the 1970s and became widely used in the 1980s. In addition, in the 1970s, a refrigerator-sized artificial pancreas called 'Biostator' was developed, which made it possible to administer insulin according to the blood glucose level. However, Biostator has the problem that it can only be used in hospitals due to its oversized size and the administration method of injecting insulin intravenously.

Research on insulin administration methods has been actively conducted, and in the late 1970s, the relatively small infusion pump 'Auto Syringe' was developed by Dean Kamen , who is known as the developer of Segway. In addition, in 1999, medical device maker Medtronic developed a blood glucose level measuring device that is embedded in the skin, eliminating the need for the operation of 'collecting blood from the fingertips and measuring the blood glucose level on a regular basis'. .. Since then, the development of real-time blood glucose measurement equipment has continued, and its accuracy is improving year by year.

According to Kovachev, the ultimate goal of diabetes treatment is to 'reproduce a healthy pancreas.' However, the following factors made it difficult to develop an artificial pancreas.

・ Blood sugar level fluctuates in a complicated manner depending on factors such as diet, exercise, and physical condition.
・ When insulin is administered from the outside, it takes 40 to 60 minutes for the blood sugar level to drop.
・ The effect of insulin varies from person to person, and even the same person has different effects depending on the timing of insulin administration.
・ Even with the most advanced blood glucose meter, the measured value may deviate for several hours.
・ It is necessary to deal with people with a wide range of lifestyles, from young people who are actively exercising to elderly people who sit all day long.

To solve these problems, algorithms have been developed to accurately predict the effects of insulin and to use glucagon, a hormone that raises blood sugar levels in addition to insulin that lowers blood sugar levels. These developments were carried out mainly by evaluating the effects in animal experiments, but in 2007, a research team led by Mr. Kovachev conducted an experiment similar to the 'clinical trial in 300 type 1 diabetic patients'. A computer simulation that can be effective has been developed, and the research speed has been dramatically increased.

In the latter half of the 2000s, with the help of the above-mentioned computer simulation to speed up research, the 'artificial pancreas that keeps measuring blood glucose levels throughout the day and administers an appropriate amount of insulin' was developed. I did. Furthermore, in 2011, a small artificial pancreas capable of web-based remote management was developed by performing calculations on an Android smartphone, and in 2016, the first commercial small artificial pancreas system ' MiniMed 670G ' was developed. This Mini Med 670G has been confirmed in clinical trials to be able to adjust insulin doses throughout the day and to have high glycemic control ability.

According to Mr. Kovachev, at the time of writing the article, 'a system that supplies insulin directly to the bloodstream by implanting an artificial pancreas in the body' is under development.