A history of closed loop systems in type 1 diabetes
Replacing the lost function of the pancreas is the “holy grail” of treatments for type 1 diabetes, where the body becomes unable to produce the insulin it needs to regulate blood sugar levels.
But the technology to do this has actually been around since the 1960s – it’s just been impractical to use on a day-to-day basis.
Systems that respond to glucose measurements and provide intravenous infusions of insulin and dextrose have actually been possible for several decades, but it’s only in recent years that miniaturisation has created systems that patients can carry around with them.
The first instance of a closed-loop insulin delivery system was developed as long ago as 1963 by Dr Arnold Kadish, of Los Angeles, and was about the size of a marine’s backpack.
The device measured venous blood glucose levels every 15 seconds and delivered either insulin or glucagon to maintain the blood glucose level within a target range.
Problems with the size of the device and its accuracy meant it was not a success, although work continued on other systems in the 1970s.
This led to groups from Canada and Germany to separately develop the first systems to be described as an “artificial pancreas”, with Albisser and colleagues and Pfeiffer and colleagues both publishing findings in 1974.
The findings from Pfeiffer’s German team led to the commercial launch of the Biostator, which consisted of a pump controlling continual blood withdrawal, a glucose analyser for continuous measurement of blood glucose concentration, a computer to calculate the amount of insulin or dextrose needed and an infusion pump for insulin and dextrose delivery.
This was backed by a printer for minute-by-minute glucose recording – and because of its bulk and requirement for the patient to be continually connected to lab equipment, was largely used as a research tool.
However, the Biostator was useful as a way to measure blood glucose levels over time and was used extensively in research until the nineties.
A team from Japan led by Motoaki Shichiri developed a wearable system with a subcutaneous glucose sensor, microcomputer, and intravenous pumps for insulin and glucagon infusions that weighed 400 grams and was storable in a pocket thanks to its small size of around 15cm.
However, it took until the mid-2000s before serious progress towards a commercial system began, starting with a definition of six levels of artificial pancreas technology from the Juvenile Diabetes Research Foundation (JDRF) in 2005.
This categorised the technology based on the level of automation and at the time all the systems were in development but not commercially available.
The first level shuts off when the user is not responding to a low-glucose alarm, whereas the top tier is a fully automated closed loop system involving several hormones.
Following the JDRF’s project there was a period where progress seemed to slow down as manufacturers struggled to meet the exacting demands of regulators, such as the FDA.
Unwilling to wait for official approval, people with type 1 diabetes and their families began to experiment with the technology available to create their own closed-loop systems. The emergence of Bluetooth technology and open-source algorithms allowed this “DIY” movement to develop ahead of approval of the first FDA-approved closed loop system.
FDA rules prevented inventors from sharing instructions on how to make these “DIY” pancreases, but there was enough information available online for other people to replicate the systems.
It took until 2016 before the FDA approved Medtronic’s MiniMed 670G hybrid closed loop system, initially in patients aged 14 years or older, which continuously delivers basal insulin or insulin boluses for management of the condition.
The system contains similar components to early attempts, except much smaller and more convenient – an insulin pump, a transmitter, a sensor, insertion device and glucose meter.
Since then, the technology has gained traction with other regulators and then with payers – in late 2023 draft guidance from England’s NICE recommended hybrid closed loop systems for patients unable to control their condition using a pump or glucose monitoring system.
Final guidance that will legally oblige the NHS to fund the technology is due to be published in December and Prof. Jonathan Benger, chief medical officer at NICE described the technology as a “game changer for people with type 1 diabetes”.
He pointed out that by keeping glucose levels within range, people are less likely to have complications such as disabling hypoglycaemia, strokes and heart attacks, which are costly to the NHS.
NICE has agreed with NHS England that all children and young people, women who are pregnant or planning a pregnancy, and those people who already have an insulin pump will be first to be offered a hybrid closed loop system as part of a five-year roll-out plan.
Building on the pioneering work outlined above, people with type 1 diabetes are able to manage their condition using technology such as that of our client, ViCentra.
As highlighted in a press release announcing the launch of its hybrid closed loop system based around its Kaleido pump, patients are beginning to feel the benefits of increasingly portable and practical systems based on miniaturised technology, that is proven in the clinic.
These systems are a huge boost psychologically to patients with type 1 diabetes, who can now focus on their lives instead of constant worrying about blood sugar levels.
As Nienke Rutgers, a person with type 1 diabetes pointed out: “Being even less preoccupied with diabetes is great, I do not have to focus on the condition, and I can get on with daily activities.”
