麻豆传媒

Adults with type 2 diabetes and end-stage renal disease requiring dialysis benefitted from an artificial pancreas in a small, randomized crossover trial.

Patients using a fully automated closed loop system spent a longer amount of time in target glucose range versus those using standard insulin therapy (52.8% vs 37.7%, respectively, P<0.001), reported Charlotte Boughton, MD, PhD, of University of Cambridge Metabolic Research Laboratories in England, and colleagues.

This equated to over 3.5 more hours every day spent in target glucose range -- 100 to 180 mg/dL (5.6 to 10 mmol/L) -- they explained in .

In addition to time spent in range, those using the closed loop system also had lower glucose levels, averaging about 27 mg/dL less (182 vs 209 mg/dL, P=0.003).

Another benefit that patients saw with the closed loop system was less time spent in hypoglycemia -- marked as a sensor glucose measure less than 70 mg/dL (median 0.12% vs 0.17%, P=0.04).

As previous studies of a closed loop system have also demonstrated, performance only improved with longer use of the system. Boughton's group suggested that "[i]t is reasonable to postulate that time in target range could improve further with a longer duration of use."

They also pointed out that these previous studies of closed loop systems have been in inpatient settings, whereas this trial managed patients in an outpatient setting in completely unrestricted, typical living conditions.

"This is the first study, which has used this fully automated system in an outpatient setting for people with type 2 diabetes, which is an important step and we anticipate this technology may also benefit the wider population with type 2 diabetes." Boughton told 麻豆传媒. "We did this study as our previous studies investigating closed loop technology in the inpatient setting showed that people who required dialysis in hospital benefited from using the system with improved glucose control during their admission."

"This was an ambitious study in a vulnerable population where diabetes management can be challenging due to the risks of high and low glucose associated with kidney failure and dialysis," she added. "We were surprised that not only did the closed loop system improve time spent with glucose in the target range, but it also reduced the time spent with low glucose levels, particularly in those who were more prone to low glucose levels."

The open-label, two-center study lasted 20 days, which was divided into the first 7-day phase and the second phase spanning days 8 through 20. A total of 26 adults with type 2 diabetes requiring dialysis were recruited from Addenbrooke's Hospital in Cambridge, and the University Hospital in Bern, Switzerland (n=17 men; nine women). The average age of the cohort was 68 and the duration of diabetes was about 20 years.

Those assigned to use the artificial pancreas used the Dexcom G6 transmitter connected to the Cambridge adaptive model predictive control algorithm to direct insulin delivery on a Dana Diabecare RS pump, automatically delivering faster-acting insulin aspart (Fiasp). The closed loop system was managed using the CamDiab's CamAPS HX closed-loop app on an unlocked Android phone, with a target glucose set at 126 mg/dL.

Roughly every 8 to 12 minutes and according to the G6 sensor's data, the algorithm would calculate an insulin infusion rate that was then wirelessly directed to the insulin pump with data automatically uploaded to the .

Those in the control group used standard insulin therapy and a masked continuous glucose monitor to measure glucose levels.

Looking just at the patients using the closed loop system, time spent in target range increased 8.1% from the first week of use to the later half of the study (47.6% vs 55.8%). Average glucose levels and time spent in hyperglycemia -- defined as a glucose reading above 180 mg/dL -- both decreased during days 8-20 of the study compared with the first week.

Of note, because all these patients were also on dialysis, there were no significant differences in glycemic outcomes on dialysis days versus non-dialysis days. However, insulin delivered by the closed loop system tended to be lower on days the patients received dialysis compared with non-dialysis days (0.29 vs 0.31 U/kg).

Comparing the closed loop patients with the standard insulin therapy patients, there was no significant difference seen in the average interdialytic weight gain (4.0 vs 3.7 lbs, P=0.55).

As for safety, only one episode of severe hypoglycemia occurred in the closed loop group, although the system wasn't operational for the 24 hours leading up to the event. Two serious adverse events occurred in the closed loop period: an event of reduced responsiveness on dialysis requiring hospital admission, as well as a COVID-19 infection requiring hospital admission.

One outcome of interest was that all participants say they were "happy to have their glucose levels controlled automatically by the closed-loop system and would recommend the closed-loop system to others," according to the authors. Also, 92% of those using the closed loop system said they spent less time having to manage their diabetes, and 87% said they were less worried about their glucose levels than when they were using standard insulin therapy. Half of these patients also reported improved sleep with the closed loop system.

The authors noted that study limitations included the small sample size because of "Brexit-related study sponsorship issues and the COVID-19 pandemic."

"We would like other clinicians to be aware that automated insulin delivery systems may be a safe and effective treatment option for people with type 2 diabetes and kidney failure in the future," Boughton concluded.

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