Closed-Loop System Improves Glucose, Quality of Life for Youth With T1D

Adolescents and young adults using a hybrid closed-loop system not only had better glycemic control, but overall better quality of life, a new trial found.

Over 6 months, individuals ages 12 to 25 with type 1 diabetes who used a hybrid closed-loop system saw a significant jump in time in target glucose range of 70 to 180 mg/dL — from 53.1% at baseline to 62.5% at study end — reported Timothy W. Jones, MD, of Perth Children’s Hospital in Western Australia, and colleagues.

Meanwhile, those who remained on conventional therapy, which consisted of either a continuous subcutaneous insulin infusion or multiple daily insulin injections with or without continuous glucose monitoring, only saw an increase from 54.6% at baseline to 56.1% at study end, for a mean adjusted difference between the two groups at study end of 6.7% (95% CI 2.7-10.8, P=0.002), the authors wrote in JAMA Pediatrics.

This mean difference was equal to a gain of 1.6 hours more a day in target range on the hybrid closed-loop system.

“The improvement in [time in range] is reported to be proportional to the time spent in closed loop, as was the case in our trial,” Jones and team highlighted.

Improvements were noticeable at all times throughout the day, but even more so at night (a mean difference of 5.4% during the day and 9.3% at night).

The benefits didn’t end there, though, as the closed-loop system also significantly reduced the time participants spent in a hypoglycemic state — defined as a blood glucose level under 70 mg/dL (difference -1.9%, 95% CI -2.5% to -1.3%), and improved glycemic variability (coefficient of variation difference -5.7%, 95% CI -10.2% to -0.9%).

However, there were no differences in the time spent in hyperglycemia between the two groups.

Beyond glucose control, adolescents using the hybrid closed-loop system experienced an improvement in diabetes-specific quality of life, as measured by the Pediatric Quality of Life Inventory, version 3 scale (difference 4.4 points, 95% CI 0.4-8.4). And while those on the closed loop generally reported less fear of hypoglycemia and less diabetes-related distress versus those on conventional therapy, these differences weren’t statistically significant.

Overall, there were no reports of severe hypoglycemia or diabetic ketoacidosis in either group over the 6 months.

This phase III trial included a total of 135 patients ages 12 to 25 (mean age 15.3 years, with 82% under age 18) — 68 who were randomized to the control group of conventional therapy and 67 who were assigned to the hybrid closed-loop system. Recruitment occurred from April 2017 to October 2019 at five tertiary pediatric diabetes centers in Australia.

All patients had type 1 diabetes for at least a year with a fasting C-peptide level of less than 0.30 ng/mL and an HbA1c of 10.5% or less on standard therapy. Exclusion criteria included having used a non-insulin glucose-lowering agent or corticosteroid within the previous 3 months or current use with any closed-loop system. Patients who didn’t speak English were also excluded.

The hybrid closed-loop system used in the study was Medtronic’s MiniMed 670G pump with a Guardian Sensor 3 glucose sensor and a Guardian Link 3 transmitter.

“The recommended [time in range] of greater than 70% was achieved in fewer than 10% of the participants at baseline on conventional therapy, highlighting the complexities of diabetes management in this cohort. With the [hybrid closed-loop] system, 31% met this target,” Jones and colleagues pointed out. “Although there was an improvement, this study highlights the existing manual interface and the conservative algorithm of the 670G that was the first commercially available version, designed for safety.”

Of note, last week the FDA announced a Class I recall of Medtronic’s MiniMed 600 series of insulin pumps, including the model 670G that contains a clear retainer ring, which can become damaged and lead to incorrect dosing. In total, the recall affected 463,464 devices in the U.S. Medtronic told MedPage Today that since November 2019, the company has replaced nearly half of the clear retainer ring pumps in use in the U.S. — including fulfilling replacement requests associated with the initial recall for clear retainer rings that were loose, damaged, or missing.

Jones and team noted that the system was safe during their trial, with no device-related adverse events. However, sensor-related skin reactions were common.

“Most youth in the trial continued to wear the sensor despite these issues for the perceived benefits of the sensor and system, but the ability to wear and tolerate a sensor can be seen as a critical step in a wider adoption of closed-loop systems,” they explained. “Sensor-wear issues highlight the need for strategies in preserving skin integrity with long-term use of technological devices.”

That being said, the authors drew attention to the fact that the “landscape of technology use is constantly evolving,” as many new versions of closed-loop systems also now deliver auto-corrections and also allow for remote monitoring of glucose.