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To hell with the hypo

8th November 2023

The latest research into hypoglycaemia was under discussion at the 59th Annual Meeting of the EASD. The ‘To hell with the hypo’ session covered topics ranging from a tool to predict nocturnal hypos and new forms of glucagon to the impact of food insecurity and how people with diabetes manage their hypo risk. Dr Susan Aldridge reports.

First, there is new hope when it comes to avoiding those dreaded nocturnal hypos. Dr Thomas Kronborg of the Steno Diabetes Center in Nordjylland explained: “I sat down with my colleagues at Steno and we discussed whether it would be useful to have some kind of alarm system based on continuous glucose monitoring (CGM) data, so that every night you could pull out your phone and see if you’re at risk of night-time hypo, rather than being woken up in middle of night with an alarm. Could we use data on what happened in the day with respect to food, insulin and exercise to predict the possibility of a hypo later on?”.

They were able to build such a predictive model and then test it in the DIAMONT study. In this randomised clinical trial involving 400 participants, the model could predict 68% of nocturnal hypos. Dr Kronborg believes that the accuracy of the model could now be improved upon by getting rid of the false positives. This new tool promises to be a useful add-on to CGM technology that could help people with diabetes take preventive action if it looks like a nocturnal hypo is on the way.   

Meanwhile, Professor Stewart Harris who is Diabetes Canada Chair in Diabetes Management at Western University, Canada, noted that little is known about how people with diabetes actually manage their risk of hypoglycaemia. So he and his team used data from the iNPHORM study to address this knowledge gap with 1,687 participants with type 1 and type 2 diabetes. The findings may explain why there is still so much hypoglycaemia, much of which is not reported to healthcare professionals – there were surprisingly low numbers taking obvious precautions against hypos. For instance, only 28% took measures to avoid hypos during exercise while 14% practised due vigilance regarding their food intake and 22% checked their blood glucose after treating a hypo. These figures were derived from the always/often response on a Likert scale.  

“There are clearly gaps in self-management of hypo risk, especially in type 2 diabetes,” Professor Harris concluded. “The results of our study can hopefully guide tailored clinical efforts and infrastructure to support positive self-management behaviour among people with diabetes who are at risk of hypoglycaemia.” 

Meanwhile, many people with diabetes will be looking forward to weekly insulins, which are currently under intense clinical development. But will a weekly dose of insulin increase the risk of hypoglycaemia? Professor Tadej Battelino from the University of Ljubljana stepped forward to reassure, with findings from a post-hoc analysis of the ONWARDS 2 and ONWARDS 4 trials of the weekly insulin icodec in people with type 2 diabetes. In ONWARDS 2, participants switched from a basal insulin to icodec, which was compared with daily insulin degludec, while ONWARDS 4 was a basal-bolus switch to icodec plus insulin aspart compared with insulin glargine and insulin aspart. 

The mean hypo duration with icodec proved to be similar to that of the comparator insulins, with median times in hypoglycaemia being 40 minutes or less. Furthermore, most episodes did not develop into level 2 hypoglycaemia. “The most important message is that, despite the long half-life of icodec, its use did not lead to prolonged duration of level 1 and 2 hypos compared with a daily insulin,” Professor Battelino concluded.

Glucagon to the rescue

Various new formulations and applications of glucagon are under development, which will be of interest to those wanting a fast and effective way of treating a hypo. One example is glucagon packaged in a nasal spray. Dr Andreas Holstein from Klinikum Lippe Detmold in Germany presented findings from the SIMPLEST study, which looked at the impact of nasal glucagon on real-life experiences of severe hypoglycaemia. 

This was a web-based survey of people treated with insulin and owning glucagon, and healthcare professionals who had prescribed it. Of the 153 people with diabetes in the study, 75% had high fear of hypoglycaemia, 49% had impaired awareness of hypoglycaemia and 64% had experienced severe hypoglycaemia, which they treated with either sugars or glucagon, mainly in the form of the nasal spray. 

The findings of SIMPLEST have been very encouraging, with participants reporting less worry when driving, less need to attend hospital with a hypo and less concern about being a burden to others, for instance. “Nasal glucagon positively affected quality of life for people with diabetes,” said Dr Holstein. “It helped them avoid fear and promoted confidence and ease.” Meanwhile, 90% of healthcare professionals in the SIMPLEST survey said that they preferred the nasal spray to reconstituted glucagon as it requires less teaching time for their patients than the traditional powder form, which has to be reconstituted with water before use.   

Then there is dasiglucagon, a ready-to-use glucagon analogue in a liquid formulation packaged in a pen, which corrects a hypo in six to eight minutes. Dr Casper Nielsen, from Gentofte Hospital in Denmark, presented findings from a trial of dasiglucagon in post-bariatric hypoglycaemia (PBH), a serious complication affecting up to 50% of those who have had bariatric surgery. 

The randomised crossover clinical trial of 120 micrograms of dasiglucagon involved 24 patients who had had Roux-en-Y gastric bypass and had PBH more than three times a week. They were treated with dasiglucagon for four weeks and the time spent in level 1 hypoglycaemia was reduced by 33% (17 minutes a day) and in level 2 hypoglycaemia by 54% (6 minutes a day). “There was no increase in time above range but a small increase in time in range, which was reassuring, and less need for rescue therapy after a hypo,” added Dr Neilsen. “In conclusion, dasiglucagon is a potentially effective new therapeutic option for treatment of PBH, although larger confirmatory studies are warranted.” 

Hypos in hospital

Severe hypoglycaemia (SH) sometimes requires hospital admission, particularly when it leads to coma, which is more likely among children as it is harder for them to communicate hypo symptoms. Dr Beata Mianowska from the Medical University of Lodz, Poland, presented her study on how the frequency of hypoglycaemic coma in children has changed over the years. 

The current rate is three to seven episodes per 100 patient-years, according to the International Society for Pediatric and Adolescent Diabetes. She measured the rate of coma per 100 patient-years for 303 participants for the period 2018-2021, using the same methodology as for previous studies for the periods 1996-1999 and 2011-2014. Rates for those periods were 8.5% and 5.3%, compared with 2.2% for the new survey. She noted that age and HbA1c did not influence the rate of coma, but longer duration of diabetes did increase the risk. Looking at time of day when the coma occurred, there has been a striking decrease in night-time hypoglycaemic coma. “The decrease in rate of childhood hypoglycaemia coma over time may be because of improvement in diabetes pharmacotherapy and advances in diabetes technology,” she concluded.

Diabetic ketoacidosis (DKA) is the other reason why people with diabetes may require hospital admission. Dr Soon Song, from Sheffield Teaching Hospitals, discussed the comorbidities, clinical characteristics and mortality outcomes among people with type 1 and type 2 diabetes who were admitted for SH or DKA emergencies between January 2019 and June 2023. He noted that most of those with SH had type 2 diabetes while those with DKA and recurrent admissions were more likely to have type 1 diabetes. And of those with type 2 diabetes admitted with DKA, 30% were on SGLT-2 inhibitors.

When it came to comorbidities, the type 2 diabetes patients tended to be older and have a higher Charlson Index score, which indicates a greater burden of comorbid conditions. These included cardiorenal disease, cognitive impairment, cancer and liver and respiratory disease. Those with type 2 diabetes were also more likely to die after the diabetic emergency and time to death was shorter. Thus, concluded Dr Song, SH and DKA can be indicators of poor long-term survival. “There is a common misconception that severe hypoglycaemia can only occur when someone is on a sulphonylurea or insulin,” he said. “However, hypoglycaemia may also be a manifestation of the comorbidity and a sign of organs shutting down, particularly the liver.” 

Food insecurity and hypos

Finally, Professor Alexandria Ratski-Leewing, a colleague of Professor Harris at Western University, returned to the iNPHORM study to examine the link between food insecurity and SH, an issue that has been poorly addressed until now. Food insecurity is defined as a consistent lack of food because of an individual’s economic situation and can be seen as a marker of low socioeconomic status. It may lead to difficulty in managing diabetes which, in turn, may increase the risk of hypoglycaemia. Professor Ratski-Leewing and her team asked the question, “In the last 12 months, did you cut the size of, or cut out, meals because of lack of money?” and found that this was so for 20% of the iNPHORM cohort.

Clinical data from iNPHORM revealed that those with food insecurity were more than twice as likely to experience SH. “This is the first study to quantify the impact of food insecurity on level 3 hypoglycaemia in the US-wide population with type 1 or type 2 diabetes who are on insulin or secretagogues,” she said. “It highlights the need for improved clinical and public health strategies to mitigate the impact of food insecurity on the health of people with diabetes.”

To learn more, enrol on the EASD e-Learning course ‘Hypoglycaemia’.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.