The artificial pancreas is a technology in development to help people with diabetes, primarily type 1, automatically and continuously control their blood glucose level by providing the substitute endocrine functionality of a healthy pancreas.
The endocrine functionality of the pancreas is provided by islet cells which produce the hormones insulin and glucagon. Artificial pancreatic technology mimics the secretion of these hormones into the bloodstream in response to the body's changing blood glucose levels. Maintaining balanced blood sugar levels is crucial to the function of the brain, liver, and kidneys. Therefore, for type 1 patients, it is necessary that the levels be kept balanced when the body cannot produce insulin itself.
The artificial pancreas is a broad term for different bio-engineering strategies currently in development to achieve these requirements. Different bio-engineering approaches under consideration include:
The endocrine functionality of the pancreas is provided by islet cells which produce the hormones insulin and glucagon. Artificial pancreatic technology mimics the secretion of these hormones into the bloodstream in response to the body's changing blood glucose levels. Maintaining balanced blood sugar levels is crucial to the function of the brain, liver, and kidneys. Therefore, for type 1 patients, it is necessary that the levels be kept balanced when the body cannot produce insulin itself.
The artificial pancreas is a broad term for different bio-engineering strategies currently in development to achieve these requirements. Different bio-engineering approaches under consideration include:
- the medical equipment approach—using an insulin pump under closed loop control using real-time feedback data from a continuous blood glucose monitor.
- the physiological approach—the development of a treatment with engineered stem cells to be integrated into the body to provide functional blood glucose regulation.
Approaches
Medical equipment
The
medical equipment approach involves combining a continuous glucose
monitor and an implanted insulin pump that can function together with a
computer-controlled algorithm to replace the normal function of the
pancreas.
The development of continuous glucose monitors has led to the progress
in artificial pancreas technology using this integrated system.
Continuous glucose monitors
Artificial pancreas feedback system
The original devices for use in type 1 diabetes were blood glucose meters.
Continuous blood glucose monitors are one of the set of devices that
make up an artificial pancreas device system, the other being an insulin
pump, and a glucose meter to calibrate the device.
Continuous glucose monitors are a more recent breakthrough and have
begun to hit the markets for patient use after approval from the FDA.
Both the traditional and the continuous monitor require manual insulin
delivery or carbohydrate intake depending on the readings from the
devices. While the traditional blood glucose meters require the user to
prick their finger every few hours to obtain data, continuous monitors
use sensors placed just under the skin on the arm or abdomen to deliver
blood sugar level data to receivers or smartphone apps as often as every
few minutes. The sensors can be used for up to fourteen days. A number of different continuous monitors are currently approved by the FDA.
The first continuous glucose monitor (CGM) was approved in December 2016. Developed by Dexcom,
the G5 Mobile Continuous Monitoring System requires users to prick
their fingers twice a day (as opposed to the typical average 8 times
daily with the traditional meters) in order to calibrate the sensors.
The sensors last up to seven days. The device uses Bluetooth technology
to warn the user either through a handheld receiver or app on a
smartphone if blood glucose levels reach below a certain point. The cost
for this device excluding any co-insurance is an estimated $4,800 a
year.
Blood glucose meter FreeStyle Libre from Abbott.
Abbott Laboratories'
FreeStyle Libre CGM was approved in September 2017. Recently, the
technology was modified to support smartphone use through the LibreLink
app. This device does not require finger pricks at all and the sensor,
placed on the upper arm, lasts 14 days. The estimated cost for this
monitor is $1,300 a year.
Dexcom's next G6 model CGM was approved in March 2018, which can
last up to ten days and does not need finger prick calibration. Like
Medtronic's monitor, it can predict glucose level trends. It is
compatible for integration into insulin pumps.
Closed-loop systems
Unlike
the continuous sensor alone, the closed-loop system requires no user
input in response to reading from the monitor; the monitor and insulin
pump system automatically delivers the correct amount of hormone
calculated from the readings transmitted. The system is what makes up
the artificial pancreas device.
Inreda Diabetic
In collaboration with the Academic Medical Centre (AMC) in
Amsterdam Inreda is developing a closed loop system with insuline and
glucagon. The initiator, Robin Koops, started to develop the device in
2004 and ran the first tests on himself. After several highly successful
trails it received the European EC license in 2016. The product is
expected to market in the second half of 2020. A smaller improved
version is scheduled for 2023.
MiniMed 670G
In September 2016, the FDA approved the Medtronic MiniMed 670G, which was the first approved hybrid closed loop system. The device senses a diabetic person's basal insulin requirement and automatically adjusts its delivery to the body.
It is made up of a continuous glucose monitor, an insulin pump, and a
glucose meter for calibration. It automatically functions to modify the
level of insulin delivery based off the detection of blood glucose
levels by continuous monitor. It does this by sending the blood glucose
data through an algorithm that analyzes and makes the subsequent
adjustments.
The system has two modes. Manual mode lets the user choose the rate at
which basal insulin is delivered. Auto mode regulates basal insulin
levels from the continuous monitor's readings every five minutes.
The device was originally available only to those aged 14 or
older, and in June 2018 was approved by the FDA for use in children aged
7–14. Families have reported better sleep quality from use of the new
system, as they do not have to worry about manually checking blood
glucose levels during the night. The full cost of the system is $3700, but patients have the opportunity to get it for less.
Ilet Bionic Pancreas
A team at Boston University working in collaboration with Massachusetts General Hospital on a dual hormone artificial pancreas system began clinical trials on their device called the Bionic Pancreas in 2008. In 2016, the Public Benefit Corporation Beta Bionics
was formed. In conjunction with the formation of the company, Beta
Bionics changed the preliminary name for their device from the Bionic
Pancreas to the iLet.
The device uses a closed-loop system to deliver both insulin and
glucagon in response to sensed blood glucose levels. While not yet
approved for public use, the 4th generation iLet prototype, presented in
2017, is around the size of an iPhone, with a touchscreen interface. It
contain two chambers for both insulin and glucagon, and the device is
configurable for use with only one hormone, or both. While trials continue to be run, the iLet has a projected final approval for the insulin-only system in 2020.
Current studies
Four
studies on different artificial pancreas systems are being conducted
starting in 2017 and going into the near future. The projects are funded
by the National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK),
and are the final part of testing the devices before applying for
approval for use. Participants in the studies are able to live their
lives at home while using the devices and being monitored remotely for
safety, efficacy, and a number of other factors.
The International Diabetes Closed-Loop trial, led by researchers from the University of Virginia,
is testing a closed-loop system called inControl, which has a
smartphone user interface. 240 people of ages 14 and up are
participating for 6 months.
A full-year trial led by researchers from the University of Cambridge started in May 2017 and has enrolled an estimated 150 participants of ages 6 to 18 years. The artificial pancreas system being studied uses a smartphone and has a low glucose feature to improve glucose level control.
The International Diabetes Center in Minneapolis, Minnesota, in collaboration with Schneider Children's Medical Center
in Petah Tikva, Israel, are planning a 6-month study that will begin in
early 2019 and will involve 112 adolescents and young adults, ages 14
to 30.
The main object of the study is to compare the current Medtronic 670G
system to a new Medtronic-developed system. The new system has
programming that aims to improve glucose control around mealtime, which
is still a big challenge in the field.
The current 6-month study lead by the Bionic Pancreas team
started in mid-2018 and enrolled 312 participants of ages 18 and above.
Physiological
The Bio-artificial pancreas: this diagram shows a cross section of bio-engineered tissue with encapsulated islet cells which deliver endocrine hormones in response to glucose.
The biotechnical company Defymed, based in France, is developing an
implantable bio-artificial device called MailPan which features a
bio-compatible membrane with selective permeability to encapsulate different cells types, including pancreatic beta cells.
The implantation of the device does not require conjunctive
immuno-suppressive therapy because the membrane prevents antibodies of
the patient from entering the device and damaging the encapsulated
cells. After being surgically implanted, the membrane sheet will be
viable for years.The cells that the device holds can be produced from
stem cells rather than human donors, and may also be replaced over time
using input and output connections without surgery.
Defymed is partially funded by JDRF, formerly known as the Juvenile
Diabetes Research Foundation, but is now defined as an organization for
all ages and all stages of type 1 diabetes.
In November 2018, it was announced that Defymed would partner
with the Israel-based Kadimastem, a bio-pharmaceutical company
developing stem-cell based regenerative therapies, to receive a two-year
grant worth approximately $1.47 million for the development of a
bio-artificial pancreas that would treat type 1 diabetes.
Kadimastem's stem cell technology uses differentiation of human
embryonic stem cells to obtain pancreatic endocrine cells. These include
insulin-producing beta cells, as well as alpha cells, which produce
glucagon. Both cells arrange in islet-like clusters, mimicking the
structure of the pancreas.
The aim of the partnership is to combine both technologies in a
bio-artificial pancreas device, which releases insulin in response to
blood glucose levels, to bring to clinical trial stages.
The San Diego, California based biotech company ViaCyte has also
developed a product aiming to provide a solution for type 1 diabetes
which uses an encapsulation device made of a semi-permeable immune
reaction-protective membrane. The device contains pancreatic progenitor cells that have been differentiated from embryonic stem cells.
After surgical implantation in an outpatient procedure, the cells
mature into endocrine cells which arrange in islet-like clusters and
mimic the function of the pancreas, producing insulin and glucagon.
The technology advanced from pre-clinical studies to FDA approval for
phase 1 clinical trials in 2014, and presented two-year data from the
trial in June 2018.
They reported that their product, called PEC-Encap, has so far been
safe and well tolerated in patients at a dose below therapeutic levels.
The encapsulated cells were able to survive and mature after
implantation, and immune system rejection was decreased due to the
protective membrane. The second phase of the trial will evaluate the
efficacy of the product. ViaCyte has also been receiving financial support from JDRF on this project.
Initiatives around the globe
In
the United States in 2006, JDRF (formerly the Juvenile Diabetes
Research Foundation) launched a multi-year initiative to help accelerate
the development, regulatory approval, and acceptance of continuous
glucose monitoring and artificial pancreas technology.
Grassroots efforts to create and commercialize a fully automated
artificial pancreas system have also arisen directly from patient
advocates and the diabetes community. Bigfoot Biomedical,
a company founded by parents of children with T1D have created
algorithms and are developing a closed loop device that monitor blood
sugar and appropriately provide insulin.
