STOCKHOLM – The artificial beta cell is moving from the lab bench to the bedside table.
These experimental closed-loop insulin systems, which deliver constantly adjusted pulses of insulin, continue to rack up research success. Tightly controlled studies have given way to more free-ranging trials conducted in diabetes camps and, now, even at home. The endpoints continue to align, providing a growing certainty that the systems regulate glucose much more efficiently than does a traditional insulin pump.
“We now have a large number of studies in patients of various types – adults, children, adolescents, and even pregnant women – and in various situations – at home, at camp, in clinics, and even in acute illness,” Dr. Lalantha Leelarathna said at the annual meeting of the European Association for the Study of Diabetes. “Compared with our current best therapy, these studies consistently show more time in target, lower mean glucose, less burden of hypoglycemia, less glucose variability, and an improvement in hemoglobin A1c.”
Dr. Lalantha Leelarathna
Not all the studies of the artificial beta-cell insulin system have been completely successful, he admitted. “We’ve had problems with sense accuracy, with device connectivity, and there is an urgent need to miniaturize these devices and integrate them so patients can use them easily. But there is no hiding the fact that there has been tremendous progress over the past 5-10 years in this field, and it’s becoming a realistic option for our patients to have these in the not-too-distant future.”
Dr. Leelarathna of the University of Manchester, England, discussed some of the newest data on the closed-loop systems, including two 12-week home-use trials, which were simultaneously published in the New England Journal of Medicine. They were conducted by the APCam Consortium and the AP@home Consortium. One examined the system’s 24-hour use in a population of adults; the other was an overnight study in children and teens. Both were randomized crossover trials that compared a closed-loop system with sensor-augmented pump therapy.
Both studies used the FlorenceD2A closed-loop system. The Florence system uses a smartphone or tablet to wirelessly communicate a model predictive algorithm to the pump. Every 12 minutes, the system calculates a new insulin infusion rate. The treat-to-target control algorithm aims to achieve glucose levels between 5.8 and 7.3 mmol/L and adjusts the actual level depending on fasting vs. postprandial status and the accuracy of model-based glucose predictions.
AP@home04
The study was conducted in the United Kingdom, Austria, and Germany; it comprised 33 adults with type 1 diabetes.
After a 4-week optimization period, the patients used either their control system or the closed-loop system day and night for 3 months. There was then a 4-week washout period, followed by 12 weeks’ use of the comparator system. The Florence system ran wirelessly off the patients’ smartphone, which was with them at all times.
The results consistently favored the closed-loop system, Dr. Leelarathna said. It significantly improved time spent in the target glucose range of 70-180 mg/dL (76% vs. 56% per 24 hours). It also reduced the time spent with glucose above 180 mg/dL (29% vs. 39%), as well as the time spent in the hypoglycemic range of less than 50 m/dL (0.3% vs. 0.4%). The mean glucose level was significantly lower (157 vs. 168 mg/dL). These improvements were achieved despite no increase in insulin (48.8 vs. 48.1 U/day).
HbA1cwas significantly improved from baseline on the closed-loop system, dropping from 7.6%-7.3%. While on the insulin pump, HbA1cwas unchanged (7.6% at both time points).
APCam08
The children’s study was conducted in three U.K. centers, and comprised 25 children and teens with type 1 diabetes. The mean HbA1c at baseline was 8.1%. The study protocol was the same, except that the children used the pumps only from midnight-8 a.m. The algorithm was transmitted to the unit via USB cable from a tablet on the bedside table.
The results were also quite similar. The closed-loop system significantly increased the time spent in the target range of 70-145 mg/dL (60% vs. 34% per 24 hours). Likewise, the time in hyperglycemia (above 145 mg/dL) was significantly reduced (37% vs. 61%). However, there was no difference in time spent in hypoglycemia.
Mean glucose level was significantly improved (146 vs. 176 mg/dL), and overnight insulin use slightly, but not significantly, reduced (7.6 vs. 7.7 U).
After the initial optimization period, the subjects’ mean HbA1c was 7.8%. This improved significantly on the closed loop system (7.6%), but rose slightly on the insulin pump (7.9%).
Although these two trials represent the longest free-living studies with the closed-loop system, they’re not the only ones, Dr. Leelarathna mentioned. A third was also presented at the meeting