Although of short duration, this well designed study shows that semi-artificial pancreas helps in reducing A1c and preventing hypoglycemia more than the usual insulin pump. A group of 29 individuals with type 1 diabetes and A1c < 7.5% were randomized to receive hybrid closed-loop system or the traditional pump therapy. Participants were followed for 4 weeks and then crossed over for another 4 weeks.
The Lancet: Diabetes and Endocrinology
Randomized, Crossover Study
Background: Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA1c <7.5%
Methods: In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA1c <7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2–4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2–4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard.
The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9–10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat.
Findings: Between March 21 -June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10.5% higher (p<0·0001) during closed-loop delivery compared with usual pump therapy (65·6% when participants used usual pump therapy vs 76·2% when they used closed-loop). Compared with usual pump therapy, closed-loop delivery also reduced the proportion of time spent in hypoglycaemia: the proportion of time with glucose concentration below 3·5 mmol/L was reduced by 65% (p<0·0001) and below 2·8 mmol/L by 76% (p<0·0001). No episodes of serious hypoglycaemia or other serious adverse events occurred.
Interpretation: Use of day-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA1c <7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies are warranted.
Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study
Lia Bally, MD, Hood Thabit, PhD, Harald Kojzar, BSc, Julia K Mader, MD, Jehona Qerimi-Hyseni, BSc, Sara Hartnell, BSc, Martin Tauschmann, MD, Janet M Allen, RN, Malgorzata E Wilinska, PhD, Thomas R Pieber, MD, Mark L Evans, MD, DrRoman Hovorka, PhD
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Intensive insulin therapy is the standard of care in the management of type 1 diabetes. Although modern insulin therapy has led to a reduction in the frequency of severe hypoglycaemic events, tight glycaemic control remains a predisposing factor to hypoglycaemia and its effect is amplified by duration of the disease. Recurrent exposure to hypoglycaemia might lead to attenuated counter-regulatory response to subsequent hypoglycaemic events and, ultimately, impaired hypoglycaemia awareness. Frequent hypoglycaemic episodes might have a profound effect on behaviour and diabetes self-management, adversely affecting quality of life.
Closed-loop insulin delivery—also known as the artificial pancreas—is a therapeutic approach that is progressing quickly. Closed-loop delivery differs from conventional pump therapy and threshold suspend technology; it has a control algorithm that autonomously increases and decreases subcutaneous insulin delivery in response to real-time sensor glucose levels.
In this study, we aimed to investigate whether day-and-night hybrid closed-loop insulin delivery—in which manual administration of prandial bolus was implemented by the user—under free-living conditions in adults with HbA1c below 7·5% can improve glucose control while alleviating the risk of hypoglycaemia, thus informing whether the use and reimbursement of closed-loop systems is justified in this particular population.
Hypoglycaemia is associated with increased morbidity and mortality in patients with type 1 diabetes. A reduction of at least 30% in risk of hypoglycaemia, as observed in our study, is considered clinically relevant.
The additional benefit of closed-loop insulin delivery in individuals with well controlled type 1 diabetes (ie, HbA1c <7·5%) is the reduction of the residual risk of complications, hypoglycaemia, and glycaemic variability, as well as the burden of self-management. Reduction of hypoglycaemic burden has benefits such as improved quality of life and reduced societal cost.
Results from participants' feedback indicate a high level of trust in the closed-loop system autonomously modulating their glucose concentrations, with the majority agreeing that the time spent on management of diabetes was reduced during the closed-loop period. However, seven (24%) of 29 participants disagreed with this statement, reflecting that user input is still needed for a hybrid closed-loop system.
The strengths of this study include the randomised, two-centre, two-country, crossover design. So far, none of the home-based studies of closed-loop insulin delivery have focused specifically on patients with HbA1c below 7·5% who might be early adopters of closed-loop technologies striving to further improve control of their diabetes.
To conclude, day-and-night closed-loop insulin delivery in adults with type 1 diabetes and HbA1c <7·5% significantly improved glycaemic control while reducing the risk of hypoglycaemia. Thus, in adults who are actively engaged with self-management, closed-loop insulin delivery might provide additional benefits, justifying its use in this particular population. The overall positive feedback from participants reflected the acceptance of closed-loop technology during daily diabetes management, albeit with some limitations to its use, which might affect user adherence and experience. Larger and longer studies are needed to validate our findings.