Artificial pancreas for type 1 diabetics – Expert reaction

An artificial pancreas can help people with type 1 diabetes smooth out blood sugar peaks and troughs, according to a new study. 

Artificial pancreasArtificial pancreas systems which automatically control insulin levels in patients with type 1 diabetes work better than other insulin treatments, according to a new review of medical trials.

Type 1 diabetes accounts for around 10 percent of the 240,000 cases of diabetes in New Zealand and can only be treated with regular injections of insulin.

Most treatments rely on patients monitoring their own blood sugar and injecting themselves with insulin when levels are low. However, a number of clinical trials have now investigated the effectiveness of a new treatment, the artificial pancreas – a man-made device that is designed to release insulin in response to changing blood sugar levels in a similar way to a human pancreas.

A new review of these studies, covering over 1000 patients, was published today in BMJ. The authors found that artificial pancreas treatment provides almost two-and-a-half extra hours of normal blood glucose levels a day, and reduces the time spent in high and low blood glucose levels.

While further research is needed to verify the findings, the researchers say these results support the view that “artificial pancreas systems are a safe and effective treatment approach for people with type 1 diabetes.” They also recommend that future research should “explore artificial pancreas use in relevant groups of people with type 2 diabetes.”

Read more about the study on scimex.org.

The Science Media Centre has asked experts to comment on the new findings and what they mean for New Zealanders.

Professor Peter Shepherd, University of Auckland and Maurice Wilkins Centre, comments:

“It is nearly 100 years since insulin was discovered. This momentous discovery turned what was once an incurable disease into one that could be controlled long term by several daily injections of insulin. This greatly improved lifespan and quality of life for people with diabetes as it allowed them to achieve some level of control of the sugar called glucose in their blood.

“However, many problems remained because several injections of insulin a day is not only painful but fails to control glucose levels as well as a healthy body would. This is because the cells in the human pancreas that make insulin are continually measuring levels of glucose in the blood and releasing just the right amount of insulin.

“While transplants of insulin-producing cells from human donors are possible, they come with many disadvantages, donors are scarce and it is a very expensive process. Similarly, many groups (including our own) are investigating methods to produce human insulin-producing cells from stem cells but it will be some time before this approach is viable.

“In the meantime, many groups have been working on developing an artificial pancreas that uses the latest advances in sensor technology and micropumps in a device that can measure blood glucose and release appropriate amounts of insulin. Dramatic progress has been made in this technology in recent years and it is on the verge of going mainstream.

“Concerns remain, however, about the efficacy and safety of such devices. The review by Bekiari et. al. goes some way to allaying these fears by summarising the data from all the trials that have used such devices to date. This summary shows very clear safety and efficacy benefits of artificial pancreases compared to current standard of care.

“This means we are one step closer to seeing these in widespread use but costs will probably mean it will be some time before they are available through Pharmac in New Zealand as the device alone costs around $10,000 and the ongoing costs of the special insulin pumps and glucose sensors will cost thousands of dollars more each year. “

Dr Brandon Orr-Walker, Endocrinologist and Diabetologist, Counties Manukau Health, comments:

“It has been nearly a hundred years since exogenous insulin therapy was first developed and made available for use to treat Type 1 diabetes. There have been considerable advances in types of insulin and delivery devices in the time since to provide improved and more predictable and reproducible dosing intensity and duration, and to allow people with type one diabetes to better control their glucose levels with the help and assistance of experienced expert practitioners. The challenges though are considerable and include technical limitations, practical limitations and funding of these solutions.

“Glucose is an essential and time-critical fuel for brain, heart and kidney function, but it is also toxic in high concentrations leading to wide-spread vascular damage over time.

“These glucose fluxes are normally ‘automatically’ controlled on a minute by minute basis in the body through a number of regulatory mechanisms, including most notably insulin release directly into the portal circulation (but also glucagon secretion which may also diminish in type 1 diabetes).

“In real life management of type 1 diabetes, intermittent subcutaneous injections or even programmed continuous subcutaneous pumps and user selected boluses with multiple finger prick testing is onerous and often difficult to adhere to, let alone approximate to physiological minute-by-minute control.

“Alternatives to intermittent finger prick glucose monitoring with continuous glucose monitoring with sensor devices are not funded in New Zealand, and generally not integrated with the insulin delivery devices that are funded. Therefore hyperglycaemia and hypoglycaemia are ongoing challenges with the latter a greater risk the more tight control is attempted in general.

“The prospect of continuous glucose monitoring being linked by programmable (and ‘learning’ from feedback via artificial intelligence) algorithms to insulin delivery, has been keenly anticipated and trial results of these approaches awaited.

“This is a rapidly developing field and the current meta-analysis is significant in including new research not included in prior pooled analyses. The results are significant and show a considerable reduction in the time spent “out of range” per day of over two hours per day, consisting of two hours less hyperglycaemia and 20 minutes less hypoglycaemia each day on average — in particular at the risky timeframe overnight compared with the comparison treatments.

“Equally significant in the NZ context is that the comparison treatments in the majority of the trials included in this analysis represent current state of the art systems such as sensor-augmented pumping (where users can manually modify insulin rates based on continuous glucose monitoring, and in some cases automatically suspend insulin for low glucose readings) which are more advanced than those currently funded in NZ.

“The trials included in the analyses were largely conducted in supervised environments with only a minority in unsupervised normal living conditions. The prospect that these devices may be of even greater advantage in peoples’ normal living arrangements, and for a wider group of people who struggle with the ongoing “manual” practices and habitual discipline in daily life required to achieve such excellent control is very real.

“People with type 1 diabetes should be very excited indeed to see these advances enter routine clinical practice, and feel reassured that there is a great rate of progress in development.

“As we are increasingly trusting, familiar and reliant on computer power and clever applications on devices we carry on our person every day for other aspects of our lives, there may be a confluence of technologies soon and ability for people with type 1 diabetes to share information with their clinicians that will enhance glucose control and safety.”

Associate Professor Rinki Murphy, Diabetologist, Auckland Diabetes Centre, Greenlane Clinical Centre; Department of Medicine, University of Auckland, comments:

“This systematic review of studies comparing artificial pancreas systems with any other type of insulin based treatment found that artificial pancreas AP was associated with increased time in the normal glucose range (around 140 minutes per day).

“This improvement was more evident overnight than during the day. The superior performance of artificial pancreas overnight is known to be due to the absence of eating.

“With intensive insulin therapy for type 1 diabetes, people need to estimate the carbohydrate content of their meals and to determine the proper insulin bolus based on their insulin to carbohydrate ratio which is quite challenging. Controlling glucose effectively after a meal still remains a challenge with the closed loop strategy in artificial pancreas systems, and presently relies on some kind of meal alert involving at least a simplified meal bolus strategy based on the carbohydrate content of the meal. The types of meal support within the different artificial pancreas systems tested were not clarified in the review paper.

“It is important to remember that the researchers summarised the glucose results from comparisons of artificial pancreas with any type of insulin-based treatment, which could overestimate the superiority of the artificial pancreas system. The two most common insulin-based treatments are multiple daily insulin injections (most commonly used by adults with type 1 DM in NZ) or the insulin pump, which are each guided either by glucose results from several capillary tests per day (most commonly used by people in NZ) or continuous real-time glucose monitoring (unfunded in NZ).

“There are certain insulin pumps which have the capacity for automatic insulin dose suspension when a low glucose threshold is reached, which are also currently unfunded in NZ.

“This review did not report the results of artificial pancreas when compared to the most intensive non-artificial pancreas management i.e.: insulin pump with CGM informed low glucose suspend, which is likely to produce more modest differences than in those studies comparing artificial pancreas with less intensive insulin management such as multiple daily insulin injections with intermittent capillary glucose monitoring.

“Besides improvements in glucose levels, we also need to consider any impacts of this technology on quality of life and its real-world cost-effectiveness, particularly when this artificial pancreas technology is released for general use outside clinical trial settings with longer term follow up.”