New closed-loop insulin systems Boughton, Charlotte K.; Hovorka, Roman
Diabetologia,
05/2021, Letnik:
64, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Advances in diabetes technologies have enabled the development of automated closed-loop insulin delivery systems. Several hybrid closed-loop systems have been commercialised, reflecting rapid ...transition of this evolving technology from research into clinical practice, where it is gradually transforming the management of type 1 diabetes in children and adults. In this review we consider the supporting evidence in terms of glucose control and quality of life for presently available closed-loop systems and those in development, including dual-hormone closed-loop systems. We also comment on alternative ‘do-it-yourself’ closed-loop systems. We remark on issues associated with clinical adoption of these approaches, including training provision, and consider limitations of presently available closed-loop systems and areas for future enhancements to further improve outcomes and reduce the burden of diabetes management.
Graphical abstract
The role of automated insulin delivery systems in diabetes is expanding. Hybrid closed-loop systems are being used in routine clinical practice for treating people with type 1 diabetes. ...Encouragingly, real-world data reflects the performance and usability observed in clinical trials. We review the commercially available hybrid closed-loop systems, their distinctive features and the associated real-world data. We also consider emerging indications for closed-loop systems, including the treatment of type 2 diabetes where variability of day-to-day insulin requirements is high, and other challenging applications for this technology. We discuss issues around access and implementation of closed-loop technology, and consider the limitations of present closed-loop systems, as well as innovative approaches that are being evaluated to improve their performance.
In adults with type 2 diabetes, the benefits of fully closed-loop insulin delivery, which does not require meal bolusing, are unclear. In an open-label, single-center, randomized crossover study, 26 ...adults with type 2 diabetes (7 women and 19 men; (mean ± s.d.) age, 59 ± 11 years; baseline glycated hemoglobin (HbA1c), 75 ± 15 mmol mol
(9.0% ± 1.4%)) underwent two 8-week periods to compare the CamAPS HX fully closed-loop app with standard insulin therapy and a masked glucose sensor (control) in random order, with a 2-week to 4-week washout between periods. The primary endpoint was proportion of time in target glucose range (3.9-10.0 mmol l
). Analysis was by intention to treat. Thirty participants were recruited between 16 December 2020 and 24 November 2021, of whom 28 were randomized to two groups (14 to closed-loop therapy first and 14 to control therapy first). Proportion of time in target glucose range (mean ± s.d.) was 66.3% ± 14.9% with closed-loop therapy versus 32.3% ± 24.7% with control therapy (mean difference, 35.3 percentage points; 95% confidence interval (CI), 28.0-42.6 percentage points; P < 0.001). Time > 10.0 mmol l
was 33.2% ± 14.8% with closed-loop therapy versus 67.0% ± 25.2% with control therapy (mean difference, -35.2 percentage points; 95% CI, -42.8 to -27.5 percentage points; P < 0.001). Mean glucose was lower during the closed-loop therapy period than during the control therapy period (9.2 ± 1.2 mmol l
versus 12.6 ± 3.0 mmol l
, respectively; mean difference, -3.6 mmol l
; 95% CI, -4.6 to -2.5 mmol l
; P < 0.001). HbA1c was lower following closed-loop therapy (57 ± 9 mmol mol
(7.3% ± 0.8%)) than following control therapy (72 ± 13 mmol mol
(8.7% ± 1.2%); mean difference, -15 mmol mol
; 95% CI, -11 to -20 mmol l
(mean difference, -1.4%; 95% CI, -1.0 to -1.8%); P < 0.001). Time < 3.9 mmol l
was similar between treatments (a median of 0.44% (interquartile range, 0.19-0.81%) during the closed-loop therapy period versus a median of 0.08% (interquartile range, 0.00-1.05%) during the control therapy period; P = 0.43). No severe hypoglycemia events occurred in either period. One treatment-related serious adverse event occurred during the closed-loop therapy period. Fully closed-loop insulin delivery improved glucose control without increasing hypoglycemia compared with standard insulin therapy and may represent a safe and efficacious method to improve outcomes in adults with type 2 diabetes. This study is registered with ClinicalTrials.gov (NCT04701424).
The possible advantage of hybrid closed-loop therapy (i.e., artificial pancreas) over sensor-augmented pump therapy in very young children with type 1 diabetes is unclear.
In this multicenter, ...randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy at seven centers across Austria, Germany, Luxembourg, and the United Kingdom. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). The primary end point was the between-treatment difference in the percentage of time that the sensor glucose measurement was in the target range (70 to 180 mg per deciliter) during each 16-week period. The analysis was conducted according to the intention-to-treat principle. Key secondary end points included the percentage of time spent in a hyperglycemic state (glucose level, >180 mg per deciliter), the glycated hemoglobin level, the mean sensor glucose level, and the percentage of time spent in a hypoglycemic state (glucose level, <70 mg per deciliter). Safety was assessed.
A total of 74 participants underwent randomization. The mean (±SD) age of the participants was 5.6±1.6 years, and the baseline glycated hemoglobin level was 7.3±0.7%. The percentage of time with the glucose level in the target range was 8.7 percentage points (95% confidence interval CI, 7.4 to 9.9) higher during the closed-loop period than during the control period (P<0.001). The mean adjusted difference (closed-loop minus control) in the percentage of time spent in a hyperglycemic state was -8.5 percentage points (95% CI, -9.9 to -7.1), the difference in the glycated hemoglobin level was -0.4 percentage points (95% CI, -0.5 to -0.3), and the difference in the mean sensor glucose level was -12.3 mg per deciliter (95% CI, -14.8 to -9.8) (P<0.001 for all comparisons). The time spent in a hypoglycemic state was similar with the two treatments (P = 0.74). The median time spent in the closed-loop mode was 95% (interquartile range, 92 to 97) over the 16-week closed-loop period. One serious adverse event of severe hypoglycemia occurred during the closed-loop period. One serious adverse event that was deemed to be unrelated to treatment occurred.
A hybrid closed-loop system significantly improved glycemic control in very young children with type 1 diabetes, without increasing the time spent in hypoglycemia. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT03784027.).
Automated Insulin Delivery in Adults Boughton, Charlotte K; Hovorka, Roman
Endocrinology and metabolism clinics of North America,
03/2020, Letnik:
49, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Hybrid closed-loop (artificial pancreas) systems have recently been introduced into clinical practice for adults with type 1 diabetes. This reflects successful translation from research studies in ...highly supervised settings to evaluation of the technology in free-living home settings. We review the different closed-loop approaches and the key clinical evidence supporting adoption of hybrid closed-loop systems for adults with type 1 diabetes. We also discuss the growing evidence for automated insulin delivery in pregnant women and in hospitalized patients with hyperglycemia. We consider the psychosocial impact of closed-loop systems and the challenges and potential future advancements for automated insulin delivery.
The artificial pancreas Boughton, Charlotte K; Hovorka, Roman
Current opinion in organ transplantation,
08/2020, Letnik:
25, Številka:
4
Journal Article
Advances in diabetes technologies have enabled the development of artificial pancreas (closed-loop) systems for people with diabetes. We review the key studies which have led to the adoption of the ...artificial pancreas in clinical practice and consider ongoing challenges and areas for future enhancements.
Studies have demonstrated safety and efficacy of closed-loop insulin delivery systems in free-living settings over periods of up to 6 months for children and adults with type 1 diabetes. Since 2017, four hybrid closed-loop systems have been approved by regulatory bodies worldwide, but these systems are not entirely automated, requiring user interaction to deliver mealtime insulin boluses. Improving usability of these devices in the real-world setting is an important challenge.
The artificial pancreas has become the gold standard for the treatment of type 1 diabetes. First-generation systems are increasingly being adopted in clinical practice, however further work is required, developing advanced systems and faster acting insulin analogues to allow complete automation and further reduce the burden of type 1 diabetes.
We evaluated the safety and efficacy of fully closed-loop insulin therapy compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis. In an open-label, multinational, ...two-center, randomized crossover trial, 26 adults with type 2 diabetes requiring dialysis (17 men, 9 women, average age 68 ± 11 years (mean ± s.d.), diabetes duration of 20 ± 10 years) underwent two 20-day periods of unrestricted living, comparing the Cambridge fully closed-loop system using faster insulin aspart ('closed-loop') with standard insulin therapy and a masked continuous glucose monitor ('control') in random order. The primary endpoint was time in target glucose range (5.6-10.0 mmol l
). Thirteen participants received closed-loop first and thirteen received control therapy first. The proportion of time in target glucose range (5.6-10.0 mmol l
; primary endpoint) was 52.8 ± 12.5% with closed-loop versus 37.7 ± 20.5% with control; mean difference, 15.1 percentage points (95% CI 8.0-22.2; P < 0.001). Mean glucose was lower with closed-loop than control (10.1 ± 1.3 versus 11.6 ± 2.8 mmol l
; P = 0.003). Time in hypoglycemia (<3.9 mmol l
) was reduced with closed-loop versus control (median (IQR) 0.1 (0.0-0.4%) versus 0.2 (0.0-0.9%); P = 0.040). No severe hypoglycemia events occurred during the control period, whereas one severe hypoglycemic event occurred during the closed-loop period, but not during closed-loop operation. Fully closed-loop improved glucose control and reduced hypoglycemia compared with standard insulin therapy in adult outpatients with type 2 diabetes requiring dialysis. The trial registration number is NCT04025775.
Aim
To evaluate the use of hybrid closed‐loop glucose control with faster‐acting insulin aspart (Fiasp) in adults with type 1 diabetes (T1D).
Research Design and Methods
In a double‐blind, ...multinational, randomized, crossover study, 25 adults with T1D using insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4% ± 0.8% 57 ± 8 mmol/mol) underwent two 8‐week periods of unrestricted living comparing hybrid closed‐loop with Fiasp and hybrid closed‐loop with standard insulin aspart in random order. During both interventions the CamAPS FX closed‐loop system incorporating the Cambridge model predictive control algorithm was used.
Results
In an intention‐to‐treat analysis, the proportion of time sensor glucose was in the target range (3.9–10.0 mmol/L; primary endpoint) was not different between interventions (75% ± 8% vs. 75% ± 8% for hybrid closed‐loop with Fiasp vs. hybrid closed‐loop with standard insulin aspart; mean‐adjusted difference −0.6% 95% CI −1.8% to 0.7%; p < .001 for non‐inferiority non‐inferiority margin 5%). The proportion of time with sensor glucose less than 3.9 mmol/L (median IQR 2.4% 1.2%–3.2% vs. 2.9% 1.7%–4.0%; p = .01) and less than 3.0 mmol/L (median IQR 0.4% 0.2%–0.7% vs. 0.7% 0.2%–0.9%; p = .03) was reduced with Fiasp versus standard insulin aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. 8.0 ± 0.8 mmol/L; p = .13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; p = .90). Total daily insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; p = .45). No severe hypoglycaemia or ketoacidosis occurred.
Conclusions
The use of Fiasp in the CamAPS FX closed‐loop system may reduce hypoglycaemia without compromising glucose control compared with standard insulin aspart in adults with T1D.
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