The 6 Stages of an Artificial Pancreas

The JDRF’s Chief Mission Officer and scientist Aaron Kowalski wrote an article published in the ADA’s Diabetes Care journal detailing the six stages or steps required by technology to bring us to an artificial pancreas. Below is a summary of the six steps and which companies have achieved these steps.

Stage 1

This step involves the insulin pump shutting off when the user fails to respond to a low glucose alarm. If a person using this stage of technology has a low blood sugar, the sensor will communicate this information to the system device which will sound off an alarm to let the user know. If the user doesn’t respond to the alarm, the system will stop all insulin delivery. This safety mechanism would help the user to not receive any more insulin in the event of a low blood sugar, helping to prevent the worsening of the situation.

Stage 2

This stage of technology minimizes low blood sugar occurrences by using warning alarms when a low blood sugar is predicted by the system. The system will reduce or stop insulin delivery based on the information it is tracking and the user-inputed low blood sugar threshold. This means that the user can define when their system will alert them–beginning with a blood sugar of 70 or 60 or whatever they deem best for them.

Stage 3

This stage of technology is like stage 2 with the addition of the ability to reduce high blood sugar. In this case, when the sensor senses blood sugar above a pre-defined high blood sugar threshold (example: 200 mg/dL) it will notify the system to automatically dose a corrective amount of insulin that is an individualized calculation by the algorithm.

Stage 4

The first hybrid closed-loop system to pass the FDA in the United States is at this stage–Medtronic’s 670G device. This system is a basal/hybrid closed-loop at all times with a manual meal assist bolus. So for example, at meal times, the user inputs the carbohydrate count of their meal and the device will dose the necessary insulin using the blood sugar information it is getting and the individualized calculation made by the integrated algorithm. Bigfoot Biomedical is currently working on a device that would be similar to this stage of technology. According to a company spokesperson, their Bigfoot smartloop system will involve many different implementation elements so it is important to realize that within each stage there are companies working on unique devices that won’t neatly fit into the mold of any of these stages. In the case of Bigfoot’s smartloop system, users will still take mealtime boluses but they won’t have to count carbs the way they do at the moment. The company intends to provide a simple user interface that helps make a general estimate.

Stage 5

At this step of the technology a manual mealtime bolus won’t be necessary and the system would be considered a fully automated closed-loop system. A user would simply begin eating their meal and the device would dose insulin according to the sensor information. At this point a user would be able to go about their life without testing and doing any of the insulin or carbohydrate calculations that people with diabetes do at the present time.

Stage 6

At this stage we would finally have a true artificial pancreas system which would be a fully automated multi-hormone closed loop system. At this stage we would have all the previous technology but also a bihormonal approach used to treat and prevent low blood sugar episodes automatically. The only current device aiming to be at this stage is Edward Damiano’s iLet device.

The Challenge Involved in Stage 6 with a Bi-Hormonal Approach

Bihormonal treatments would treat high and low blood sugars, dose for any food and corrections–all without the user having to do anything. A properly functioning body does all these things automatically. This is why this level of technology would be considered an artificial pancreas. Nothing before this stage truly qualifies, although many see previous stages as huge milestones that help the journey to stage 6.There is a major hurdle involved at stage 6. The issue of a substance that can be used within a device to raise blood sugar levels as needed. Glucagon is normally what the body excretes to raise a low blood sugar and would be an ideal couple to insulin in an artificial pancreas system. Currently however, there is still a need for a soluble pumpable glucagon, as well as a dual-chambered pump, and cost is still a limiting factor.Researchers are currently exploring another multi-hormone approach in the use of insulin and amylin. Kowalski writes that “Amylin plays a important role physiologically by suppressing glucagon production, contributing to regulation of gastric emptying, and impacting satiety.” He adds that amylin can be given using the analog pramlintide and that “Pilot studies of multihormone AP systems using insulin and pramlintide have demonstrated impressive results,” Making this pumpable is also an issue as well as cost effectiveness.

Insulin Needs an Upgrade, Too

There are a few other things that need to be accomplished in order to realize an artificial pancreas.Currently, the volume of insulin is too great. In order to miniaturize the artificial pancreas system, insulin needs to become more concentrated so that less is needed for the same effect. Currently, Insulin glargine (Lantus) has managed to reduce volume in its new formulation, marketed as Toujeo.Insulin is also currently too slow. In an artificial pancreas, insulin needs to be released in a way that mimics the body’s release of insulin which means it needs to work very quickly so that blood sugar levels are handled as they begin to rise.Until insulin is enabled to become faster, there will still be a need to input carbohydrate amount into any automated insulin delivery device.

Better Health Outcome = Artificial Pancreas Accessibility

Lastly, for an artificial pancreas to be accessible, it needs to prove a better health outcome. Better outcomes include an improved A1c and a reduced burden at a cost that is consistent with the benefits it provides. In other words, if blood sugar management isn’t substantially improved and the cost of the system is substantially higher, it may be difficult for the healthcare system to justify.As Kowalski writes, “patients, health care professionals, and payers” all need to receive good value as key stakeholders in order for the adoption of new artificial pancreas technology.