Artificial Pancreas: What You Should Know

Artificial Pancreas: What You Should Know…
Written by Amy Tenderich | Published on May 10, 2016

If you pay attention to diabetes news at all, you’re surely hearing the term ‘Artificial Pancreas’ (or ‘closed loop system’ or ‘bionic pancreas’) a lot these days.

And if you live with diabetes yourself, well-meaning family and friends may even be asking if you have one of these yet. Make no mistake: this is a teaching moment for everyone involved.

{Editor's Note: This is mainly a primer for the uninitiated, but also a useful overview for anyone effected by diabetes.}

What Is an ‘Artificial Pancreas’ to Begin With?
Although ‘Artificial Pancreas’ sounds like a single appliance that you would just plug into your body, the fact is: we are not there yet.

It’s taken researchers decades to get to the point where they can connect various diabetes devices, using a combination of cables and wireless technology, to create a system that can mimic what a healthy pancreas does, by monitoring glucose levels and delivering insulin as needed.

So right now, a so-called ‘Artificial Pancreas’ is essentially an insulin pump connected to a continuous glucose monitor (CGM), controlled via some kind of receiver (usually a smartphone) using sophisticated software algorithms to make the whole thing work.

The idea is to automate blood glucose control as much as possible, so the wearer no longer has to take fingerstick blood sugar readings, and then do complex math to determine how much insulin to dose, or how much to reduce insulin delivery based on low readings. Some systems can even shut off insulin delivery automatically based on low blood sugar readings detected by the CGM. And some systems are experimenting with carrying glucagon in the pump alongside insulin, to bring blood sugar up when necessary.

These systems are still being studied, and as of this writing (April 2016), there is no commercial AP product on the market yet. But incredible strides are being made, and new groups seem to be emerging all the time to work on this exciting advancement.

Products included in current AP systems:

an insulin pump, which provides a continuous flow of insulin into the body via an “infusion site” or small cannula inserted in the skin
a continuous glucose monitor (CGM) that takes ongoing blood sugar readings via a little sensor worn on the skin, that has its own separate cannula from the pump. There are currently two CGMs on the market in the U.S., from Dexcom and Medtronic
a controller (usually an iPhone) that includes the display screen where users can see glucose data
algorithm software, the “brain” of the system, that crunches the numbers to predict where glucose levels are headed and then tells the pump what to do
sometimes glucagon, a hormone that rapidly increases blood glucose, used here as an antidote to hypoglycemia (low blood sugar)

Who’s Creating These AP Systems?
Here’s a list of companies involved in developing a market-ready AP system, in alphabetical order:

Beta Bionics - Born out of the University of Boston iLet Bionic Pancreas Project, Dr. Ed Damiano and team have recently formed a commercial company to take their system to market.

Bigfoot Biomedical - Established in 2014 by former JDRF CEO Jeffrey Brewer, Bigfoot has hired some of the most prominent AP entrepreneurs and even purchased the IP (intellectual property) and San Mateo, CA, office space from now-defunct insulin pump company Asante Solutions.

CellNovo & Diabeloop - a European pump company and French research consortium developing and testing new AP systems in the UK and France.

Dexcom - the leading CGM sensor technology from this San Diego-based company is at the heart of a large majority of AP systems under development, including some DIY (do-it-yourself) systems being cobbled together by citizen hackers. To enable further development, Dexcom integrated an AP algorithm into their G4 product in 2014, and has signed device integration agreements with insulin pump makers Insulet (OmniPod) and J&J Animas.

Dose Safety - a Seattle-based startup developing a sophisticated controller for use in AP systems.

DreaMed Diabetes - an Israel-based startup established in 2014 as a spin-off the DREAM International Consortium, in order to commercialize the Artificial Pancreas technology behind its Glucositter software.

Insulet Corp. and Mode ACG - the Boston-based manufacturers of the tubeless OmniPod insulin pump announced integration with the Dexcom CGM in 2014, and recently struck a deal with AP software firm Mode AGC (Automated Glucose Control LLC) to develop and incorporate their advanced AP algorithm in the system.

J&J Animas - the insulin pump maker launched its combo pump and Dexcom CGM system (the Animas Vibe) in 2014. There has been speculation that its much-awaited AP system could hit the market early than expected.

Medtronic Diabetes - the insulin pump market leader and only company that manufacturers both a pump and CGM device, it famously launched its combo system with low-glucose suspend (530G) in 2014, the first product approved through a new FDA designation intended to smooth the regulatory path for these devices. Medtronic also signed an exclusive agreement in 2015 to use artificial pancreas software Glucositter in its future systems. Medtronic’s next-gen “hybrid” AP system (670G) is expected to be first to market in 2017.

Pancreum - a visionary startup established by a former Insulet engineer who aims to create a three-part modular design to make the AP system more flexible and useful for patients.

Tandem Diabetes Care - makers of the innovative iPhone-ish t:slim insulin pump are developing an integrated pump-CGM system featuring both the predictive hypoglycemia algorithm and a predictive hyperglycemia (high blood sugar) algorithm. They have already completed in-house studies, and are working with the FDA to obtain IDE (Investigational Device Exemption) approval for further studies.

TypeZero Technologies - A Charlottesville, VA-based startup that spun off from years of closed loop research and development of an AP system at the University of Virginia (UVA). They are working to commercialize what the UVA originally called DiAs (short for Diabetes Assistant system).

Artificial Pancreas Lingo
Here’s the skinny on some of the key terminology involved:

Algorithms - in case you’re unfamiliar, an algorithm is a set of step-by-step mathematical instructions that solve a recurrent problem. In the AP world, there are a bunch of different approaches to this -- which is a shame actually, because standardizing the protocols and reporting metrics would be hugely beneficial to both physicians (for evaluating data) and patients (for getting access to systems that provide a choice of interchangeable components).

Closed-loop - per definition, an automatic control system in which an operation, process, or mechanism is regulated by feedback. In the diabetes world, a closed-loop system is essentially an Artificial Pancreas, where insulin delivery is regulated by feedback from an algorithm based on CGM data.

Dual Hormone - this refers to AP systems that contain both insulin and glucagon, the hormone that has the opposite effect on blood sugar levels.

UI (user interface) - a technology term that refers to everything designed into a device with which a human being may interact -- the display screen, colors, buttons, lights, icon characters, help messages, etc. Researchers have come to realize that a poorly designed UI could be the deal-breaker that could keep patients from using an AP system. Therefore, a great deal of effort is currently going into the design of the UI.

Low-Glucose Suspend (LGS) or Threshold Suspend - that feature allowing an AP system to automatically shut down insulin delivery in the case that a low blood sugar threshold is reached. This capability is key to creating an AP that can truly control glucose levels.

#WeAreNotWaiting - the hashtag that has become a rally cry among citizen hackers moving ahead with medical device innovation without waiting for doctors, pharma, or the FDA to give them the go-ahead. This grassroots initiative has been very influential in accelerating innovation, including AP development.

#OpenAPS - a homemade “do-it-yourself” Artificial Pancreas system created by citizen hackers Dana Lewis and Scott Leibrand. Their incredible work has spawned a movement, as more and more patient entrepreneurs begin to use and iterate on this system. The FDA has acknowledged OpenAPS, and is still grappling with how to respond.

Some Important Things to Know About AP Systems
Here are some important facts about AP development, in no particular order:

FDA and JDRF are Pushing Hard on AP Progress
Actually, they’ve been pushing on this for a full decade!

Back in 2006, JDRF established the Artificial Pancreas Project Consortium (APPC), a multi-year, multi-million dollar initiative to accelerate AP development. This got a big boost when that same year, FDA also named AP technology as one of its “Critical Path” initiatives to drive innovation in scientific processes.

Then in March 2011, JDRF proposed that the FDA issue guidance to help further accelerate development. JDRF worked with clinical experts to draft those initial recommendations, which were released in December 2011.

In March of 2012, the FDA gave the green light to the very first outpatient clinical trial of an AP system.

Clinical Trials for Artificial Pancreas AboundBionic Pancreas clinical trials
As it stands today, there are several hundred sites around the country and around the world conducting AP clinical trials -- many of them in “outpatient” settings, meaning study participants are not confined to a hospital or clinic.

Two of the newest trials, that kicked off in January of 2016, are expected to pave the way for FDA approval of a commercial product by proving the safety and efficacy of an AP system over the long-term (6 months to a year) “in the patient’s natural environment.”

There’s No Such Thing as “Non-Invasive”
Lots of folks unfamiliar with diabetes are surprised to hear that all this equipment still pierces our skin, because they keep hearing about breakthrough “non-invasive” diabetes technology.

While it is true that new inhalable insulin hit the market in the past year (MannKind’s Afrezza), so far that mealtime-only insulin has not been sufficient for use in an Artificial Pancreas system. Current AP systems use a pump that delivers insulin through a small “subcutaneous” (under the skin) cannula.

It’s also been a dream for many decades to create a way to measure glucose without poking the skin, but we are not there yet either. So far, attempts to measure BG through the skin itself, through sweat, and even through your eyes have not been successful. But the experts are still hard at work trying. Note that Google is investing in developing contact lenses for glucose measurement. Cross your fingers (or your eyes?) for that one!

User Involvement & Risk Are Key Issues
The FDA, whose role it is to worry about patient safety, is understandably concerned about the risks involved with an automated system that delivers insulin without human intervention. Or without much human intervention… It is unclear to what extent an AP user will have to “announce” upcoming meals or exercise. And most systems do include alarms to encourage user oversight and intervention when needed.

The FDA also took a very long time to approve the first step towards automation, an ‘‘insulin suspend” feature in the Medtronic system that shuts off insulin delivery for two hours overnight when a low blood sugar threshold is reached and the user does not respond to alarms.

While the FDA’s thinking was that stopping insulin delivery poses a risk to the patient, most people who take insulin see this differently.

Many patients’ thinking (including ours at the ‘Mine) goes like this:

Insulin is already a very risky drug. Patients make mistakes dosing it all the time! So having a smart software system that can make informed recommendations is a huge advantage. Also, if someone is experiencing nocturnal hypoglycemia, there is more risk involved in NOT shutting off insulin delivery than in allowing it to proceed.

As with almost all medical treatments, there are risks and trade-offs involved. But we patients whose lives depend on insulin feel that an AP system would actually REDUCE the day-to-day risks that we already face with severe hypoglycemia and suboptimal glucose control.