The artificial pancreas (closed-loop system) addresses the unmet clinical need for improved glucose control whilst reducing the burden of diabetes self-care in type 1 diabetes. Glucose-responsive ...insulin delivery above and below a preset insulin amount informed by sensor glucose readings differentiates closed-loop systems from conventional, threshold-suspend and predictive-suspend insulin pump therapy. Insulin requirements in type 1 diabetes can vary between one-third–threefold on a daily basis. Closed-loop systems accommodate these variations and mitigate the risk of hypoglycaemia associated with tight glucose control. In this review we focus on the progress being made in the development and evaluation of closed-loop systems in outpatient settings. Randomised transitional studies have shown feasibility and efficacy of closed-loop systems under supervision or remote monitoring. Closed-loop application during free-living, unsupervised conditions by children, adolescents and adults compared with sensor-augmented pumps have shown improved glucose outcomes, reduced hypoglycaemia and positive user acceptance. Innovative approaches to enhance closed-loop performance are discussed and we also present the outlook and strategies used to ease clinical adoption of closed-loop systems.
Type 1 diabetes mellitus (T1DM) represents 5-10% of diabetes cases worldwide. The incidence of T1DM is increasing, and there is no immediate prospect of a cure. As such, lifelong management is ...required, the burden of which is being eased by novel treatment modalities, particularly from the field of diabetes technologies. Continuous glucose monitoring has become the standard of care and includes factory-calibrated subcutaneous glucose monitoring and long-term implantable glucose sensing. In addition, considerable progress has been made in technology-enabled glucose-responsive insulin delivery. The first hybrid insulin-only closed-loop system has been commercialized, and other closed-loop systems are under development, including dual-hormone glucose control systems. This Review focuses on well-established diabetes technologies, including glucose sensing, pen-based insulin delivery, data management and data analytics. We also cover insulin pump therapy, threshold-based suspend, predictive low-glucose suspend and single-hormone and dual-hormone closed-loop systems. Clinical practice recommendations for insulin pump therapy and continuous glucose monitoring are presented, and ongoing research and future prospects are highlighted. We conclude that the management of T1DM is improved by diabetes technology for the benefit of the majority of people with T1DM, their caregivers and guardians and health-care professionals treating patients with T1DM.
Type 1 diabetes is a lifelong disease with high management burden. The majority of people with type 1 diabetes fail to achieve glycemic targets. Algorithm-driven automated insulin delivery ...(closed-loop) systems aim to address these challenges. This review provides an overview of commercial and emerging closed-loop systems.
We review safety and efficacy of commercial and emerging hybrid closed-loop systems. A literature search was conducted and clinical trials using day-and-night closed-loop systems during free-living conditions were used to report on safety data. We comment on efficacy where robust randomized controlled trial data for a particular system are available. We highlight similarities and differences between commercial systems.
Study data shows that hybrid closed-loop systems are safe and effective, consistently improving glycemic control when compared to standard therapy. While a fully closed-loop system with minimal burden remains the end-goal, these hybrid closed-loop systems have transformative potential in diabetes care.
Improvements in sensor accuracy, greater convenience and ease of use, and expanding reimbursement have led to growing adoption of continuous glucose monitoring (CGM). However, successful utilization ...of CGM technology in routine clinical practice remains relatively low. This may be due in part to the lack of clear and agreed-upon glycemic targets that both diabetes teams and people with diabetes can work toward. Although unified recommendations for use of key CGM metrics have been established in three separate peer-reviewed articles, formal adoption by diabetes professional organizations and guidance in the practical application of these metrics in clinical practice have been lacking. In February 2019, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address this issue. This article summarizes the ATTD consensus recommendations for relevant aspects of CGM data utilization and reporting among the various diabetes populations.
Recent advances in diabetes technology have led to the development of closed-loop insulin delivery systems for the management of type 1 diabetes. Several such systems are now commercially available ...for children and young people. While all available systems have been shown to improve glycaemic control and quality of life in this population, qualitative data also highlights the challenges in using closed-loop systems, which vary among different pediatric age-groups. Very young children require systems that are able to cope with low insulin doses and significant glycaemic variability due to their high insulin sensitivity and unpredictable eating and exercise patterns. Adolescents' compliance is often related to size and number of devices, usability of the systems, need for calibrations, and their ability to interact with the system. Given the speed of innovations, understanding the capabilities and key similarities and differences of current systems can be challenging for healthcare professionals, caregivers and young people with type 1 diabetes alike. The aim of this review is to summarize the key evidence on currently available closed-loop systems for children and young people with type 1 diabetes, as well as commenting on user experience, where real-world data are available. We present findings on a system-basis, as well as identifying specific challenges in different pediatric age-groups and commenting on how current systems might address these. Finally, we identify areas for future research with regards to closed-loop technology tailored for pediatric use and how these might inform reimbursement and alleviate disease burden.
Advances in diabetes technology have led to significant improvements in the quality of life and care received by individuals with diabetes. Despite this, achieving tight glycemic control through ...intensive insulin therapy and modern insulin regimens is challenging because of the barrier of hypoglycemia, the most feared complication of insulin therapy as reported by patients, caregivers, and physicians. This article outlines the individual components of the closed-loop system together with the existing clinical evidence. The artificial pancreas prototypes currently used in clinical studies are reviewed as well as obstacles and limitations facing the technology.
Improvements in accuracy of real-time continuous glucose monitoring facilitate the development of closed-loop systems consisting of a continuous glucose monitor, a control algorithm, and an insulin ...pump. Closed-loop systems can be divided according to the way meal delivery is handled as "fully closed-loop" or "closed-loop" with meal announcement systems. Depending on the subcutaneous (sc) or intravenous (iv) body interface, three major types of closed-loop systems are recognised, (i) sc sensing and sc delivery system, (ii) the iv sensing and intraperitoneal delivery system, and (iii) the iv glucose sensing and iv insulin delivery system. Given the current research focus, this review centres on the sc-sc closed-loop approach, which has the greatest potential for a near-future commercial exploitation as recognised by the JDRF Artificial Pancreas Project. Other approaches utilising intraperitoneal or intravenous sensing/delivery are also discussed. Closed-loop systems may revolutionise diabetes management but their introduction is likely to be gradual starting from simpler applications such as hypoglycaemia prevention or overnight glucose control progressing to more complex approaches such as 24/7 glucose control. The most important question is what is achievable with existing technologies and when the first generation of closed-loop systems will find its way into clinical practice.
Automated closed-loop insulin delivery, also referred to as the 'artificial pancreas', has been an important but elusive goal of diabetes treatment for many decades. Research milestones include the ...conception of continuous glucose monitoring in the early 1960s, followed by the production of the first commercial hospital-based artificial pancreas in the late 1970s that combined intravenous glucose sensing and insulin delivery. In the past 10 years, research into the artificial pancreas has gained substantial momentum and focused on the subcutaneous route for glucose measurement and insulin delivery, which reflects technological advances in interstitial glucose monitoring and the increasing use of the continuous subcutaneous insulin infusion. This Review discusses the design of an artificial pancreas, its components and clinical results, as well as the advantages and disadvantages of different types of automated closed-loop systems and potential future advances. The introduction of the artificial pancreas into clinical practice will probably occur gradually, starting with simpler approaches, such as overnight control of blood glucose concentration and temporary pump shut-off, that are adapted to more complex situations, such as glycemic control during meals and exercise.
Closed-loop systems have been used to optimise insulin delivery in children with diabetes, but they have not been tested in neonatal intensive care. Extremely preterm infants are prone to ...hyperglycaemia and hypoglycaemia; both of which have been associated with adverse outcomes. Insulin sensitivity is notoriously variable in these babies and glucose control is time-consuming, with management requiring frequent changes of dextrose-containing fluids and careful monitoring of insulin treatment. We aimed to evaluate the feasibility of closed-loop management of glucose control in these infants.
Single-centre feasibility study with a randomised parallel design in a neonatal intensive care unit. Eligibility criteria included birth weight <1200 g and <48 hours of age. All infants had subcutaneous continuous glucose monitoring for the first week of life, with those in the intervention group receiving closed-loop insulin delivery in a prespecified window, between 48 and 72 hours of age during which time the primary outcome was percentage of time in target (sensor glucose 4-8 mmol/L).
The mean (SD) gestational age and birth weight of intervention and control study arms were 27.0 (2.4) weeks, 962 (164) g and 27.5 (2.8) weeks, 823 (282) g, respectively, and were not significantly different. The time in target was dramatically increased from median (IQR) 26% (6-64) with paper guidance to 91% (78-99) during closed loop (p<0.001). There were no serious adverse events and no difference in total insulin infused.
Closed-loop glucose control based on subcutaneous glucose measurements appears feasible as a potential method of optimising glucose control in extremely preterm infants.
Summary Background Closed-loop systems link continuous glucose measurements to insulin delivery. We aimed to establish whether closed-loop insulin delivery could control overnight blood glucose in ...young people. Methods We undertook three randomised crossover studies in 19 patients aged 5–18 years with type 1 diabetes of duration 6·4 years (SD 4·0). We compared standard continuous subcutaneous insulin infusion and closed-loop delivery (n=13; APCam01); closed-loop delivery after rapidly and slowly absorbed meals (n=7; APCam02); and closed-loop delivery and standard treatment after exercise (n=10; APCam03). Allocation was by computer-generated random code. Participants were masked to plasma and sensor glucose. In APCam01, investigators were masked to plasma glucose. During closed-loop nights, glucose measurements were fed every 15 min into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. During control nights, patients' standard pump settings were applied. Primary outcomes were time for which plasma glucose concentration was 3·91–8·00 mmol/L or 3·90 mmol/L or lower. Analysis was per protocol. This trial is registered, number ISRCTN18155883. Findings 17 patients were studied for 33 closed-loop and 21 continuous infusion nights. Primary outcomes did not differ significantly between treatment groups in APCam01 (12 analysed; target range, median 52% IQR 43–83 closed loop vs 39% 15–51 standard treatment, p=0·06; ≤3·90 mmol/L, 1% 0–7 vs 2% 0–41, p=0·13), APCam02 (six analysed; target range, rapidly 53% 48–57 vs slowly absorbed meal 55% 37–64, p=0·97; ≤3·90 mmol/L, 0% 0–4 vs 0% 0–0, p=0·16), and APCam03 (nine analysed; target range 78% 60–92 closed loop vs 43% 25–65 control, p=0·0245, not significant at corrected level; ≤3·90 mmol/L, 10% 2–15 vs 6% 0–44, p=0·27). A secondary analysis of pooled data documented increased time in the target range (60% 51–88 vs 40% 18–61; p=0·0022) and reduced time for which glucose concentrations were 3·90 mmol/L or lower (2·1% (0·0–10·0) vs 4·1% (0·0–42·0); p=0·0304). No events with plasma glucose concentration lower than 3·0 mmol/L were recorded during closed-loop delivery, compared with nine events during standard treatment. Interpretation Closed-loop systems could reduce risk of nocturnal hypoglycaemia in children and adolescents with type 1 diabetes. Funding Juvenile Diabetes Research Foundation; European Foundation for Study of Diabetes; Medical Research Council Centre for Obesity and Related Metabolic Diseases; National Institute for Health Research Cambridge Biomedical Research Centre.
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