Hypoglycaemia and diabetes technology
Advances in diabetes technology should help reduce the frequency of hypoglycaemia and the distress it can cause but does the clinical evidence for this stack up? And what about the psychological barriers to the successful use of diabetes technology? Both aspects were under discussion at the recent meeting of the International Hypoglycaemia Study Group. Dr Susan Aldridge reports.
There are many automated insulin delivery (AID) products, mostly using closed-loop with manual mealtime bolusing. All tend to show increased time in range of around 10%, reduced hyperglycaemia and hypoglycaemia, improved quality of life, decreased mean glucose values and decreased glucose variability. Professor Tim Jones, of the University of Western Australia, reviewed the clinical evidence on how AID impacts hypoglycaemia.
One of the early studies was the Diabetes Camp study, with 54 participants, where there were seven hypos in the AID group and 22 in the control group. Another hospital/clinic study involving afternoon exercise showed a significant reduction in overnight hypos on AID. More recently, there was a six-month, randomised controlled trial in Australia, involving 120 adults on either AID or manual insulin and fingerprick testing. This showed that AID does offer significant protection against hypoglycaemia exposure, as measured by time in range. “Clearly, there are still some limitations to prevention of hypoglycaemia by AID systems, as they reduce it, but do not eradicate it,” said Professor Jones.
Addressing hypos through improved technology
One of the limitations of AID – as far as hypoglycaemia is concerned – arises from insulin pharmacokinetics. It acts for ‘too long’ in an AID system because it continues to be absorbed from the subcutaneous site. There are also counter-regulatory hormone deficits in people with diabetes, and predisposing factors, such as exercise, alcohol, diet, missed insulin and sometimes a combination of all of these, which come into play and precipitate a hypo.
There are various strategies for reducing, or even eliminating, hypos with AID. A more physiological insulin delivery route, such as via the peritoneum, might help, as would faster-acting insulin or a dual-hormone system, although this would require a more complicated pump.
Then there is a prospect of automatic detection of sleep and exercise, with corresponding adjustment to insulin delivery. Finally, you can never have too much patient and clinician education when it comes to preventing or eliminating hypos.
There is one instance, though, where current AID technology has really hit the mark – it has had a big impact on nocturnal seizures. “These are very rare on closed-loop, whereas in the past they were much more common,” said Professor Jones. “With a sensor-augmented pump with low glucose suspend, the incidence of nocturnal seizures in people with impaired awareness of hypoglycaemia was reduced to zero.”
Addressing fear of hypoglycaemia
It is not just the number of hypos that AID can prevent that is important. It’s also about whether these systems can improve people’s confidence about hypoglycaemia. “We asked our patients what worries them about having a low,” said Professor Jones. “Some of the comments were disturbing – concern about passing out and dying, going so low that you go into a coma, being alone when you have a hypo. So we have to consider if closed-loop can decrease this fear of hypoglycaemia, as this is an important quality-of-life issue for people with diabetes.”
In a randomised clinical trial involving 120 adolescents, AID improved time in range compared with controls, although not as much as is seen in adults. Quality of life also improved, but there was no significant impact on fear of hypoglycaemia. “So this is more complex than just reducing hypoglycaemia exposure and needs to be dealt with appropriately,” said Professor Jones.
What about impaired awareness of hypoglycaemia? In a six-week trial of closed-loop, the time at glucose less than 3.9 mmol/l was reduced from 5.2% to 1.7%, and time at glucose less than 3 mmol/l went from 1.9% to 0.3%. However, there was no improvement in hypoglycaemia awareness, despite decreased exposure to it. So, again, as with fear of hypos, there is a need to think of effective strategies to address lack of awareness beyond just technology use, Professor Jones concluded.
Psychology, AID and hypoglycaemia
Some people with diabetes get more benefit from AID than others and some avoid it altogether. Dr Linda Gonder-Frederick, Associate Professor of Research in Psychiatric Medicine at the University of Virginia, looked at the psychological factors involved in the successful use of diabetes technology. “From a psychologist’s perspective, it’s a very complicated process,” she said. “It involves adoption, continuation of use and outcomes.”
According to the technology adoption theory, which was not developed with diabetes in mind but applies to it very well, adoption and continuation depend on ease of use, usefulness and trust, all of which are subjective and individual.
A study of readiness to use technology in people with type 2 diabetes showed five different profiles, from high to low readiness – this included medium-high readiness, but with high levels of diabetes distress, and also medium-high readiness, but with low health literacy. This suggests that support to start on AID, with the goal of reducing hypoglycaemia and associated distress, should be individualised with these profiles in mind.
There is also the issue of perceived benefit of technology vs the burden associated with its use. “This is an important concept in health-belief models,’ said Dr Gonder-Frederick. “Behaviour is an outcome of that benefit vs burden analysis. For example, for many adolescents, the perceived burden of wearing something on your body that others can see overcomes the perceived benefit of using it.”
One interesting study shows that perceived psychological benefit may sometimes be more important than actual clinical benefit. A group of 158 multiple daily injection users with less than optimal control started on CGM and, after 24 weeks, there was an improvement in diabetes distress and confidence about hypoglycaemia that was not related to glycaemia outcomes. This contrasts with the studies discussed above by Tim Jones, which suggest fewer hypos does not necessarily equate with less fear and greater awareness. These different findings maybe show how variable people’s experience of diabetes technology and hypoglycaemia can be.
Sometimes, people do not continue with CGM and insulin pumps. For instance, one study involving adolescents on closed-loop found that 30% of them discontinued its use within three to six months. The major reason given was that the system was too time-consuming to use. A survey showed that ease of use is very important going forward. Alarms and discomfort can both cause problems that might lead someone to give up on their technology. “This shows that people with diabetes need ongoing support, not just to get started on technology,” said Dr Gonder-Frederick. “Often, people have unrealistic expectations about AID. For instance, if it’s called an ‘artificial pancreas’, that gives the impression that if they use these devices they’re not going to have to think about their insulin very much. So it’s very important to have an alignment between expectations and experience.”
In another study, those with best outcomes from AID were the ones who gave themselves more meal and correction boluses. “This was a nice example of diabetes engagement,” said Dr Gonder-Frederick. “Putting in time and effort is still a requirement after starting to use the most sophisticated diabetes technology if you want to achieve the very best results.”
Finally, she looked at the A2A (Attitudes to Awareness) tool from Stephanie Amiel’s lab. “What they found with folks who were still having problems with severe hypoglycaemia was that they prioritised avoidance of hyperglycaemia and hypoglycaemia concerns were minimised,” she said. “This tells us that, even with use of the most sophisticated technology, those beliefs and psychological factors are still going to be in operation and may interfere with people achieving the goals they would like to achieve from using technology.”
Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy