Looking at the future of diabetes care? Dual-hormone pump therapy at ATTD 2017

I recently travelled to Paris to present at the 10th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD). While the conference is primarily focused on biomedical science and new technologies and treatments, there is also a significant focus on psychosocial aspects of patient interaction with new diabetes technologies such as ‘artificial pancreas’ systems for people with type 1 diabetes. Artificial pancreas systems link wearable glucose sensors with a smartphone-mounted algorithm that tells a wearable insulin pump how much insulin to deliver to maintain glycaemic control at any given time. My presentation focused on the psychosocial experiences of women using artificial pancreas systems during pregnancy, a particularly challenging time but also one in which women are especially motivated to maintain tight control of their glucose levels. In a recent mixed-methods study (interviews, questionnaires and biomedical data) embedded within an artificial pancreas trial, we found that women experienced both benefits and burdens from artificial pancreas usage. We also found that women slightly overestimated the benefit they received from the system, and in particular that those who ended the study with more positive attitudes to technology also overestimated their benefit by a larger amount. As such, our findings reveal a need to manage expectations and ensure that patients do not have unrealistic expectations about how much the system will do (or about how little they will need to do).

To date, the majority of biomedical and psychosocial research has focused on single-hormone (insulin) systems like the one described above. Systems like this have achieved impressive levels of control in comparison with user-controlled pump therapy, even when such therapy is combined with continuous glucose monitoring. Some of our participants described their experience of using the system as being like having a functioning pancreas.

Physiologically, however, glycaemic control is maintained in people with healthy pancreases not just by secretion of insulin by pancreatic beta cells, which serves to lower blood sugar levels, but also by secretion of hormones such as glucagon, which serves to raise blood sugar levels. Glucagon is released by pancreatic alpha cells in response to low blood glucose concentrations, and causes the liver to release glucose into the bloodstream by converting stored glycogen into glucose. Glucagon’s glucose-raising effect leads naturally to the idea of a dual-hormone artificial pancreas system, in which insulin is administered to lower blood glucose levels and glucagon (or amylin analogues such as pramlintide) is administered to raise them.

For some researchers, the dual-hormone approach is the future of diabetes care and the best hope for a fully-automated system that reduces the need for user input. (Most artificial pancreas systems in development currently require users to announce meals and exercise in order to avoid hyper- and hypoglycaemic excursions, and are therefore described as ‘hybrid’ systems.) Teams in Boston (Ed Damiano, Steven Russell and colleagues) and Montreal (Ahmad Haidar and colleagues) are currently developing and testing dual-hormone systems using insulin and glucagon. Early results presented at ATTD by Russell and Haidar show promising levels of control, although these have generally been achieved in controlled conditions over short time-scales and with relatively wide target glucose levels. The Boston team have recently been awarded significant funding, and a pivotal trial of the iLet dual-hormone system (and single-hormone system) is due to start in 2018. (Pramlintide also shows promise, as discussed by Stuart Weinzimer at ATTD, but as pramlintide is currently only available in injection form and requires a dose nine times that of insulin, it is not a viable solution at present.)

Not everyone is convinced by dual-hormone systems, however. Presenting soon after Damiano and Haidar was Remi Rabasa-Lhoret of the Montreal Diabetes Research Center, who introduced a well-received sceptical note into proceedings by outlining a number of significant issues relating to glucagon or amylin analogues in dual-hormone contexts. Putting aside the fact that at present glucagon is not obtainable in a stable liquid formulation, some of the most immediate concerns relate to patient safety. Since dual-hormone studies have been short-duration, we presently lack reliable data on the long-term physiological impact of using dual-hormone diabetes therapy, both in terms of the general diabetes population and in terms of particularly at-risk subgroups such as pregnant women, young children, and individuals with other concurrent conditions. Side-effects may include nausea and other gastro-intestinal complaints in addition to unknown impacts on multiple organs including the heart, the brain and the liver. These effects may be differentially experienced by users of different systems, since the systems currently in development use a wide range of glucagon dosage levels.

Safety concerns also arise from the additional complexity of dual-hormone systems and particularly from the risk, absent in single-hormone systems, of patients mixing up insulin and glucagon with potentially disastrous consequences. From an economic point of view, designing and manufacturing more complex dual-chamber pumps and providing two kinds of hormone are likely to incur significant new costs for health providers – costs which may be impossible to recoup from resulting health benefits. And from a user point of view, many patients (and especially those with a long experience of self-care) may not wish to use entirely automated systems, preferring to retain the higher degree of user input present in single-hormone systems. As such, there is a variety of reasons for thinking that dual-hormone systems may not be the best option for automated diabetes therapy in routine care. They may prove to be useful for particular sub-populations, such as people with persistent problematic hypoglycaemia. On the whole, however, sticking with single-hormone systems may turn out to be simpler, safer, more economical, and more user-friendly.

Photo credit: Simon Callaghan Photography

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