A semi-automated insulin delivery system improved glycemic control in young children with type 1 diabetes aged 1 to 7 years without increasing hypoglycemia.
“Hybrid closed-loop” systems — comprised of an insulin pump, a continuous glucose monitor (CGM), and software enabling communication that semi-automates insulin delivery based on glucose levels — have been shown to improve glucose control in older children and adults.
The technology, also known as an artificial pancreas, has been less studied in very young children even though it may uniquely benefit them, say the authors of the new study, led by Julia Ware, MD, of the Wellcome Trust–Medical Research Council Institute of Metabolic Science and the University of Cambridge, UK. The findings were published online January 19 in the New England Journal of Medicine.
“Very young children are extremely vulnerable to changes in their blood sugar levels. High levels in particular can have potentially lasting consequences to their brain development. On top of that, diabetes is very challenging to manage in this age group, creating a huge burden for families,” she said in a University of Cambridge statement.
There is “high variability of insulin requirements, marked insulin sensitivity, and unpredictable eating and activity patterns,” Ware and colleagues note.
“Caregiver fear of hypoglycemia, particularly overnight, is common and, coupled with young children’s unawareness that hypoglycemia is occurring, contributes to children not meeting the recommended glycemic targets or having difficulty maintaining recommended glycemic control unless caregivers can provide constant monitoring. These issues often lead to…reduced quality of life for the whole family,” they add.
Except for Mealtimes, Device Is Fully Automated
The new multicenter, randomized, crossover trial was conducted at seven centers across Austria, Germany, Luxembourg, and the UK in 2019-2020.
The trial compared the safety and efficacy of hybrid closed-loop therapy with sensor-augmented pump therapy (that is, without the device communication, as a control). All 74 children used the CamAPS FX hybrid closed-loop system for 16 weeks, and then used the control treatment for 16 weeks. The children were a mean age of 5.6 years and had a baseline A1c of 7.3% (56.6 mmol/mol).
The hybrid closed-loop system consisted of components that are commercially available in Europe: the Sooil insulin pump (Dana Diabecare RS) and the Dexcom G6 CGM, along with an unlocked Samsung Galaxy 8 smartphone housing an app (CamAPS FX, CamDiab) that runs the Cambridge proprietary model predictive control algorithm.
The smartphone communicates wirelessly with both the pump and the CGM transmitter and automatically adjusts the pump’s insulin delivery based on real-time sensor glucose readings. It also issues alarms if glucose levels fall below or rise above user-specified thresholds. This functionality was disabled during the study control periods.
Senior investigator Roman Hovorka, PhD, who developed the CamAPS FX app, explains in the University of Cambridge statement that the app “makes predictions about what it thinks is likely to happen next based on past experience. It learns how much insulin the child needs per day and how this changes at different times of the day.”
“It then uses this [information] to adjust insulin levels to help achieve ideal blood sugar levels. Other than at mealtimes, it is fully automated, so parents do not need to continually monitor their child’s blood sugar levels.”
Indeed, the time spent in target glucose range (70-180 mg/dL) during the 16-week closed-loop period was 8.7 percentage points higher than during the control period (P < .001).
That difference translates to “a clinically meaningful 125 minutes per day,” and represented around three quarters of their day (71.6%) in the target range, the investigators point out.
The mean adjusted difference in time spent above 180 mg/dL was 8.5 percentage points lower with the closed-loop, also a significant difference (P < .001). Time spent below 70 mg/dL did not differ significantly between the two interventions (P = .74).
At the end of the study periods, the mean adjusted between-treatment difference in A1c was –0.4 percentage points, significantly lower following the closed-loop compared with the control period (P < .001).
That percentage point difference (equivalent to 3.9 mmol/mol) “is important in a population of patients who had tight glycemic control at baseline. This result was observed without an increase in the time spent in a hypoglycemic state,” Ware and colleagues note.
Median glucose sensor use was 99% during the closed-loop and 96% during the control periods. During the closed-loop periods, the system was in closed-loop mode 95% of the time.
This finding supports longer-term usability in this age group and compares well with use in older children, they say.
One serious hypoglycemic episode, attributed to parental error rather than system malfunction, occurred during the closed-loop period. There were no episodes of diabetic ketoacidosis. Rates of other adverse events didn’t differ between the two periods.
“CamAPS FX led to improvements in several measures, including hyperglycemia and average blood sugar levels, without increasing the risk of hypos. This is likely to have important benefits for those children who use it,” Ware summarized.
Sleep Quality Could Improve for Children and Caregivers
Reductions in time spent in hyperglycemia without increasing hypoglycemia could minimize the risk for neurocognitive deficits that have been reported among young children with type 1 diabetes, the authors speculate.
In addition, they note that because 80% of overnight sensor readings were within target range and less than 3% were below 70 mg/dL, sleep quality could improve for both the children and their parents. This, in turn, “would confer associated quality-of-life benefits.”
“Parents have described our artificial pancreas as ‘life-changing’ as it meant they were able to relax and spend less time worrying about their child’s blood sugar levels, particularly at nighttime. They tell us it gives them more time to do what any ‘normal’ family can do, to play and do fun things with their children,” observed Ware.
The CamAPS FX has been commercialized by CamDiab, a spin-out company set up by Hovorka. It is currently available through several NHS trusts across the UK, including Cambridge University Hospitals NHS Foundation Trust, and is expected to be more widely available soon.
The study was supported by the European Commission within the Horizon 2020 Framework Program, the NIHR Cambridge Biomedical Research Centre, and JDRF. Ware had no further disclosures. Hovorka has reported acting as consultant for Abbott Diabetes Care, BD, Dexcom, being a speaker for Novo Nordisk and Eli Lilly, and receiving royalty payments from B. Braun for software. He is director of CamDiab.
N Engl J Med. Published online January 19, 2022. Abstract
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.
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