Simon O’Neill’s quarterly round-up – by Simon O’Neill
In a new, regular series of blogs, Simon O’Neill, Diabetes UK’s Director of Health Intelligence and Professional Liaison, rounds up the latest diabetes technologies, medicines, treatments and research developments. Simon was diagnosed with Type 1 diabetes in 1992.
For people experiencing severe hypos, glucagon is often the answer. Glucagon is a naturally occurring hormone that, like insulin, is produced in the pancreas but which has the opposite effect to insulin, raising blood glucose levels quickly. Unfortunately, in people with Type 1 diabetes, the natural glucagon response is often blunted so glucagon may need to be given by a third party. Unlike an insulin injection, glucagon is a more complex procedure. It can be quite unstable in solution so, currently, the carer has to draw up sterile water in a syringe, mix that with powdered glucagon and then administer the mix through an intramuscular injection. However, various companies are in the trial stages of easier ways of getting glucagon in to the system.
Zosano Pharma is just starting a phase 2 trial with a patch-based glucagon delivery system. The idea is to deliver glucagon through a coin-sized patch that is applied to the skin. Early studies suggest this microneedle delivery method can raise glucose just as fast as injected glucagon (starting in about 5-10 minutes). The new trial will compare this, much simpler, delivery system to standard needle-based glucagon injections.
Locemia have already completed phase 3 clinical trials of their intranasal glucagon delivery system (similar to a nasal spray for a cold). The single dose device has a small plunger on the bottom that, when pressed, releases glucagon powder up a nostril. The glucagon is then absorbed in the nasal passages without the person with diabetes having to sniff it. In the trial it proved to be as effective as a standard glucagon injection in raising blood glucose although it took about five minutes longer to have the desired effect. The product is expected to launch in 2016/17 if they can get the necessary approvals.
Biodel are developing a simpler glucagon device that still requires the powdered glucagon to be mixed with sterile water, but does this automatically as the pen device is opened, making it simpler for carers to use. Phase 3 trials are expected to start later this year.
And finally Xeris are also developing a ready-to-inject form of glucagon for severe hypoglycaemia but, interestingly, are also developing a mini-dose pen for mild to moderate hypoglycemia. This would be used by the person with diabetes themselves to correct a hypo, without having to eat or drink any carbohydrates. Their assumption is that this would give a more accurate correction and help prevent the rollercoaster many people experience after a mild hypo. The development, which is already in phase 2 trials, is interesting as they appear to have been able to create a stable, pre-mixed form of glucagon which is ready to use. They are also developing a version of this for use in the artificial pancreas, to counter balance the delivery of insulin.
Dual Chamber Insulin/Glucagon Pump
The Bionic Pancreas group at Boston have revealed a prototype dual-hormone (insulin and glucagon) device called iLet. The prototype device features a touchscreen interface, chambers for both insulin and glucagon, built-in Dexcom CGM and an integrated control algorithm, and wireless CGM calibration via a paired blood glucose meter. This is a major improvement over the current device being used in research, which requires two pumps (one each for insulin and glucagon) and a Dexcom receiver connected to a phone which runs the algorithms. The algorithm is designed to learn about the individual’s insulin requirements to better manage diabetes control.
The plan is to use the new device in a human factors study with a custom-designed infusion set in 2016.
Visual impairment apps
Novartis have recently launched two apps which will work with the Apple Watch and other devices aimed at people with visual impairment. ViaOpta Nav is a ‘turn-by-turn’ app that provides spoken directions and guidance and vibration alerts for people walking with visual impairment. The app can also share the person’s exact location with their carers. The ViaOpta Daily app helps people identify objects in their field of vision, by pointing a device’s camera at an object. This includes things like currency and colours. The apps are available globally in at least 11 languages.
Nao is a 60cm tall robot, who is being used to help children with diabetes accept the condition and become more confident about their future with diabetes.
ALIZ-E – an €8.3M, 4.5 year research study, funded by the European Commission and led by Plymouth University – has shown young people are more inclined to perform tasks related to their condition if prompted to do so by a friendly interactive robot.
The robots are equipped with specially designed speech recognition software to enable them to interact with the child and deliver personalised responses. It appears to be the individualisation that helps children relate to the robot and interact with it. For example, the robot makes mistakes which the children can pick up on and realise that diabetes isn’t about perfection all the time.
The prototype robots were initially tested at a hospital in Milan, the Fondazione Centro San Raffaele, and following initial success trials were then carried out in 11 other centres across Europe on children between the ages of 7 and 11. The tasks performed by the robots include keeping a diary in which they record food intake, insulin injections and blood glucose levels, with the study showing youngsters provide more information if a robot has prompted them to do so. For those on return visits, the robot helps children – through a number of quizzes and games – to understand diabetes more in a way they can understand.
The next stage is to see whether the robots could assist children with other medical conditions, such as autism, or act as classroom assistants aiding pupils who may be in danger of falling behind their peers. In one school, the robot taught eight-year-olds about prime numbers – researchers were able to show that a robot teacher results in a noticeable improvement over teaching using only computers.
If you’d like to see a short video of the robots in action with young children with diabetes, go to the Plymouth University website.
Benefits of pumps
A Swedish study has concluded that the use of CSII (insulin pumps) has great benefit on cardiovascular disease and overall mortality. The study looked at outcomes of 2,441 people treated with insulin pump therapy and 15,727 treated with multiple daily injections for a follow-up period of 6.8 years. Insulin pump treatment was associated with a reduction of 45 per cent for fatal coronary heart disease, 42 per cent for fatal cardiovascular disease, and 27 per cent for all-cause mortality.
The authors admit that they do not know why these benefits are seen but have put forward various theories which require further exploration. It could be attributable to continuous infusion of insulin; the presumption that pump users will be undertaking more intensified glucose monitoring; that they will have increased motivation to control blood glucose; or that they have a better understanding of Type 1 diabetes.
Another possible explanation is that pump users tend to have fewer severe hypos, which could explain why insulin pump treatment is associated with a reduced cardiovascular mortality. Such episodes can trigger cardiac arrhythmias and lead to heart attacks. Administration of insulin by continuous infusion has been reported to reduce the frequency of severe hypos compared with administration of insulin by multiple daily injections. But it may also be the case that treatment with a pump might lead to a lower frequency and duration of hyperglycaemia, leading to a reduced long term occurrence of microvascular and cardiovascular complications.
Whatever the case, it would seem that this is further evidence of the benefits of pump use. In Sweden about 50 per cent of children and 20-25 per cent of adults use pumps. In the UK the latest figures were 19 per cent of children and only 6 per cent of adults.