Synthetic pancreases may be the wave of the future for type 1 diabetics, but are they safe and effective in adolescents?
Adolescents with type 1 diabetes have a high rate of nonadherence, frequently miss bolus doses and have the highest discontinuation rate with insulin pumps. The artificial pancreas, or hybrid closed-loop insulin delivery device, has shown promising results in adult patients with regard to increased adherence, better glycemic control and fewer episodes of hypoglycemia. However, at-home overnight studies of the synthetic pancreas in adolescents have not been conducted until now.
The primary endpoint of this “free-living,” crossover, randomized clinical trial was to test whether a hybrid closed-loop insulin delivery device, used day and night without remote monitoring, is safe and effective in adolescents with type 1 diabetes compared to sensor-augmented insulin pump therapy. This was measured by analyzing the amount of time spent within the plasma glucose target range of 3.9-10 mmol/L. Secondary outcomes included lowering of mean plasma glucose, time spent above target glucose level, and hypoglycemic “burden” defined as an area under the curve of <3.5 mmol/L.
The 12 participants (8 males and 4 females) in this study were recruited from a pediatric diabetes clinic in Cambridge, UK. To be included in the study, they had to be between the ages of 10-18 years old, have type 1 diabetes, be a current user of an insulin pump for at least 3 months, and have an A1c of <11%. Baseline A1c levels and non-hypoglycemia C-peptide levels were taken once the participants were enrolled using ion exchange high performance liquid chromatography and chemiluminescence immunoassay respectively.
There was a two-week run-in phase in which participants were trained to use either the DANA Diabecare R insulin pump or the Florence D2A closed-loop system with insulin aspart or lispro. After the run-in, participants underwent two seven-day trial periods, separated by a four-week washout period in which they could use the study insulin pump, but continuous glucose monitoring was stopped. For both study groups, a prandial bolus calculator was utilized for mealtime and glucose levels were monitored with four daily finger sticks and continuous monitoring in the pump and closed-loop system respectively. The analysis was conducted according to an intention-to-treat protocol. The primary outcome utilized a least square regression model and outcomes were calculated using “GStat” software. P values were two-sided and results were considered significant for p<0.05.
The closed-loop system yielded results with plasma glucose in the target range 72% of the time compared to only 53% of the time with the sensor-augmented pump therapy (P<0.001). The mean plasma glucose was 8.7 mmol/L with the closed-loop compared to 10.1 mmol/L with the pump (P=0.028) and the time spent above the target plasma glucose level was likewise reduced in the closed-loop group (P=0.005). There was no statistical difference in hypoglycemic events between the two therapies.
While this study had a small patient population, short duration and little use of the closed-loop system during exercise, it confirms the data previously collected in studies with adult participants. Furthermore, it confirms that closed-loop insulin delivery systems are safe and efficacious for unsupervised day and night insulin delivery in adolescents. Closed-loop systems may be the answer to better adherence and tighter glycemic control in adolescents.
- The day and night hybrid closed-loop insulin delivery system increases plasma glucose control in comparison to sensor-augmented insulin pump therapy in adolescents.
- The closed-loop system does not increase hypoglycemic events when compared to sensor-augmented insulin pumps.
- Closed-loop therapy may significantly improve outcomes in poorly controlled adolescents.
Researched and prepared by Devon Brooks, Doctor of Pharmacy Candidate LECOM College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE
Tauschmann, Martin, Allen, Janet M., Wilinska, Malgorzata E., et al. “Day-and-night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes: a free-living, randomized clinical trial.” Diabetes Care. Web. 9 Feb. 2016.