Twelve-week, at-home use of a closed-loop system, also referred to as “the artificial beta cell,” appears to improve glucose control and reduce hypoglycemia in adults and in children with type 1 diabetes, as compared with sensor-augmented pump therapy, according to new data presented at EASD 2015, the annual meeting of the European Association for the Study of Diabetes.
The findings from two studies were simultaneously published in the New England Journal of Medicine.
“These two studies have a number of strengths,” said study investigator Lalantha Leelarathna, PhD, who is a consultant diabetologist and honorary senior lecturer at Manchester Royal Infirmary and the University of Manchester in the United Kingdom. “These are the longest closed-loop studies to date by some margin.”
For these multicenter, crossover, randomized, controlled studies, the Leelarathna and colleagues compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes under free-living home conditions.
The closed-loop system differs from conventional pump therapy and threshold-suspend approaches in that it employs a control algorithm that allows for continual increases and decreases in the subcutaneous delivery of insulin, based on real-time sensor glucose levels.
As part of the investigation, the closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. All the patients in these studies had type 1 diabetes, as defined by the World Health Organization (WHO), and all had received insulin-pump therapy for at least 6 months.
In the two studies, the patients used the closed-loop system for a 12-week period followed by sensor-augmented pump therapy (control) for a 12-week period. The two treatment interventions were separated by a washout period that lasted 4 to 6 weeks in adults and 3 to 4 weeks in children and adolescents.
The primary endpoint for the investigation in the adult study was the proportion of time that the glucose levels were between 70 mg/dL and 180 mg/ dL. For children and adolescents, the primary endpoint was the proportion of time that glucose levels were between 70 mg/dL and 145 mg/ dL.
Results showed that the proportion of time in which glucose levels were in the target range was 11.0 percentage points (95% CI, 8.1-13.8) greater with the use of the closed-loop system day and night than with sensor-augmented pump therapy in adults. Additionally, mean glucose level was lower (difference, –11.3 mg/dL; 95% CI, –17 to –6) lower during the closed-loop phase than during the sensor-augmented pump therapy phase.
The area under the curve for the period when the glucose level was less than 63 mg/dL (39% lower; 95% CI, 24-51) and the mean glycated hemoglobin level (difference, –0.3%; 95% CI, –0.5 to –0.1) were also lower during the closed-loop phase, according to the data.
Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the sensor-augmented pump therapy by 24.7 percentage points (95% CI, 20.6-28.7).
In addition, the mean nighttime glucose level was lower (difference, −29 mg/dL; 95% CI, –39 to –20), as was the area under the curve for the period in which the day-and-night glucose levels were less than 63 mg/dL was lower by 42% (95% CI, 4-65).
During the closed-loop phase, three severe hypoglycemic events occurred when the closed-loop system was not in use.
“There is generalizability of the results,” said Leelarathna, who presented the findings at the meeting. “There was no remote close monitoring or supervision. There were no restrictions on participants’ dietary intake, physical activity or geographical movement.”
The researchers concluded that there are several advantages of a closed-loop system due to its responsive, graduated modulation of insulin delivery, both below and above the preset pump regimen. They report that this allows for improvements in the proportion of time spent in target glucose range and the lowering of the mean glucose level without increasing the risk for hypoglycemia.
These new data extend and confirm findings from previous, shorter trials during free daily living in adults and adolescents, the researchers noted.
- Leelarathna L et al. The artificial beta cell: European research. Presented at: EASD 2015; Sept. 14-18, 2015; Stockholm.
- Thabit H et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1509351.