User:Elenadob/sandbox

The artificial pancreas is a medical 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 in islet cells which produce the hormones insulin and glucagon. Artificial pancreatic technology must mimic 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.

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—an insulin pump in a closed loop control system using real-time feedback data from a continuous blood glucose monitor.
• the biological approach—the development of a treatment with engineered stem cells which potentially could be integrated into the body to increase functional beta cell count.

Medical equipment

Existing Technologies

The medical equipment approach involves combining a continuous glucose monitor with an implanted insulin pump that can function together to replace the normal function of the pancreas.

The original devices for use in type 1 diabetes were blood glucose meters. Continuous blood glucose monitors are a more recent breakthrough and have begun to hit the markets for patient use after approval from the FDA. Both of these types of monitors require manual insulin delivery or carbohydrate intake depending on the reading from these 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 ten days. Four different continuous monitors are currently approved by the FDA.

Continuous Glucose Monitors

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 device. 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 coinsurance is an estimated $4,800 a year.

Abbott Laboratories' FreeStyle Libre CGM was approved in September 2017. It does not support smartphone use. This device does not require finger pricks at all, and the sensor, placed on the upper arm, lasts 10 days. The estimated cost for this monitor is $1,300 a year.

In March 2018, the FDA approved the Guardian Connect, a CGM by Medtronic, their first monitor independent from any linked insulin pumps. The device requires two finger pricks per day to be calibrated, and sensors can be worn on the upper arm or abdomen for seven days. Their system can be accessed by smartphone, and is able to predict the future glucose levels of the patient and can warn the user anywhere from 10 minutes to an hour before the level becomes too high or low. The estimated total cost is $3355.50 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.

MiniMed 670G

In September 2016 the FDA approved the Medtronic MiniMed 670G, which was the first approved hybrid closed loop system which 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 chose 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 in during the night The full cost of the system is $3700, but patients have the opportunity to get it for less.

The Bionic Pancreas

A team at Boston University working in collaboration with Massachusetts General Hospital on a dual hormone artificial pancreas device began clinical trials on their device call the Bionic Pancreas in 2008.In 2016, the Public Benefit Corporation Beta Bionics was formed alongside the replacing of the preliminary name for the device from Bionic Pancreas to the iLet. The device uses a closed-loop system to delivery 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.

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 while 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.

The International Diabetes Center in Minneapolis, Minnesota, and Schneider Children's Medical Center in Petah Tikva, Israel are planning a 6-month study which will begin in early 2019 and 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.

Biological/Physiological?

The biotech 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-supressive 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 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.

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.

(I was thinking about deleting the Initiatives Around the Globe section--there is very little in it and I don't think it's really pertinent information. Let me know what you think)