Recent advances in closed-loop insulin delivery.

Since the discovery of insulin 100 years ago, we have seen considerable advances across diabetes therapies. The more recent advent of glucose-responsive automated insulin delivery has started to revolutionise the management of type 1 diabetes in children and adults. Evolution of closed-loop insulin delivery from research to clinical practice has been rapid, and multiple systems are now commercially available. In this review, we summarise key evidence on currently available closed-loop systems and those in development. We comment on dual-hormone and do-it-yourself systems, as well as reviewing clinical evidence in special populations such as very young children, older adults and in pregnancy. We identify future directions for research and barriers to closed-loop adoption, including how these might be addressed to ensure equitable access to this novel therapy.

'Smart' insulin-delivery technologies and intrinsic glucose-responsive insulin analogues.

Insulin replacement therapy for diabetes mellitus seeks to minimise excursions in blood glucose concentration above or below the therapeutic range (hyper- or hypoglycaemia). To mitigate acute and chronic risks of such excursions, glucose-responsive insulin-delivery technologies have long been sought for clinical application in type 1 and long-standing type 2 diabetes mellitus. Such 'smart' systems or insulin analogues seek to provide hormonal activity proportional to blood glucose levels without external monitoring. This review highlights three broad strategies to co-optimise mean glycaemic control and time in range: (1) coupling of continuous glucose monitoring (CGM) to delivery devices (algorithm-based 'closed-loop' systems); (2) glucose-responsive polymer encapsulation of insulin; and (3) mechanism-based hormone modifications. Innovations span control algorithms for CGM-based insulin-delivery systems, glucose-responsive polymer matrices, bio-inspired design based on insulin's conformational switch mechanism upon insulin receptor engagement, and glucose-responsive modifications of new insulin analogues. In each case, innovations in insulin chemistry and formulation may enhance clinical outcomes. Prospects are discussed for intrinsic glucose-responsive insulin analogues containing a reversible switch (regulating bioavailability or conformation) that can be activated by glucose at high concentrations.

DIY artificial pancreas: A narrative of the first patient and the physicians' experiences from India.

BACKGROUND AIMS: Frustrated with the slow-pace of innovations in diabetes technologies, the type 1 diabetes community have started closing the loop by themselves to automate insulin delivery. While the regulatory and ethical concerns over the systems are still high, these have contributed to enhanced glycemic control characterized by improved estimated HbA1c and time-in-range above 90% as for many users. Our objective is to provide the real-world experience of the first successful patient from India on the Do-It-Yourself Artificial Pancreas (DIYAP) and the perspective of her physicians. METHODS: A narrative recounting of a personal experience on DIYAP. The patient completed a Hypoglycemia Fear Survey II and Diabetes Quality of Life instrument before and after looping. RESULTS: The patient emphasized the personal/social benefits and the concerns of using the system. Looping has produced a clinically meaningful difference in the quality of life, better sleep patterns, and reduced the disease management burden. We also highlighted the relevant perspectives of the physicians to give deeper insights into the aspect. CONCLUSION: The patient highlighted better time-in-range, negligible time spent in hypoglycemia, and superior Quality of Life. Globally, more and more patients are adopting this technology; therefore, real-life patient stories will enlighten the medical community.

Transforming type 1 diabetes: the next wave of innovation.

The discovery of insulin in 1921 enabled pharmaceutical production of animal insulins for the treatment of people with type 1 diabetes by 1922. The last several decades have witnessed enormous scientific progress in the therapy of type 1 diabetes, yet some developments have been incremental, and insulin is not a cure. Herein, I highlight key scientific advances potentially poised to improve the quality of life and treatment outcomes in type 1 diabetes. These innovations range from newer insulin analogues to the development of smart insulins, oral and weekly insulins, glucose sensors and closed-loop insulin-delivery devices, as well as strategies for durable human beta cell replacement coupled with selective immune manipulation to preserve beta cell function. Finally, progress in the prediction and prevention of type 1 diabetes highlights the ongoing challenges and potential for altering the natural history of the disease or eliminating type 1 diabetes altogether.

New closed-loop insulin systems.

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.

[Artificial pancreas: where are we in 2020†?] / Pancréas artificiel†: où en sommes-nous en 2020†?

The artificial pancreas is a system coupling an automatic insulin infusion according to a continuous glucose monitoring. It is mainly intended for type 1 diabetic patients. Many advances in this area have led to the commercialization of so-called hybrid artificial pancreas devices. These devices always require human intervention to announce the amount of carbohydrates ingested at each meal. The complete fully automated system, called closed loop, is being evaluated thanks to the improvement of prediction algorithms. This paper aims to describe the progress of the artificial pancreas in 2020.

Le pancréas artificiel (PA) est un système couplant la perfusion automatique d'insuline en fonction de la concentration du glucose enregistrée de manière continue. Il s'adresse, principalement, aux patients diabétiques de type 1. Les nombreux progrès en la matière ont permis d'aboutir à la commercialisation de systèmes de PA dits hybrides. Ceux-ci nécessitent toujours une intervention humaine pour l'annonce de la quantité de glucides ingérés aux différents repas. La fermeture complète de la boucle aboutissant à un système autorégulé est en cours d'évaluation grâce à l'amélioration des algorithmes de prédiction. Cet article fait le point sur l'état d'avancement du PA en 2020.

Evolution of Diabetes Technology.

Technological innovations have fundamentally changed diabetes care. Insulin pump use and continuous glucose monitoring are associated with improved glycemic control along with a better quality of life; automated insulin-dosing advisors facilitate and improve decision making. Glucose-responsive automated insulin delivery enables the highest targets for time in range, lowest rate and duration of hypoglycemia, and favorable quality of life. Clear targets for time in ranges and a standard visualization of the data will help the diabetes technology to be used more efficiently. Decision support systems within and integrated cloud environment will further simplify, unify, and improve modern routine diabetes care.

Automated Insulin Delivery in Adults.

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.

Do-It-Yourself Artificial Pancreas System and the OpenAPS Movement.

People with diabetes have been experimenting with and modifying their own diabetes devices and technologies for many decades in order to achieve the best possible quality of life and improving their long-term outcomes, including do-it-yourself (DIY) closed loop systems. Thousands of individuals use DIY closed loop systems globally, which work similarly to commercial systems by automatically adjusting and controlling insulin dosing, but are different in terms of transparency, access, customization, and usability. Initial outcomes seen by the DIY artificial pancreas system community are positive, and randomized controlled trials are forthcoming on various elements of DIYAPS technology.

Real-World Use of Do-It-Yourself Artificial Pancreas Systems in Children and Adolescents With Type 1 Diabetes: Online Survey and Analysis of Self-Reported Clinical Outcomes.

BACKGROUND: Patient-driven initiatives have made uptake of Do-it-Yourself Artificial Pancreas Systems (DIYAPS) increasingly popular among people with diabetes of all ages. Observational studies have shown improvements in glycemic control and quality of life among adults with diabetes. However, there is a lack of research examining outcomes of children and adolescents with DIYAPS in everyday life and their social context. OBJECTIVE: This survey assesses the self-reported clinical outcomes of a pediatric population using DIYAPS in the real world. METHODS: An online survey was distributed to caregivers to assess the hemoglobin A1c levels and time in range (TIR) before and after DIYAPS initiation and problems during DIYAPS use. RESULTS: A total of 209 caregivers of children from 21 countries responded to the survey. Of the children, 47.4% were female, with a median age of 10 years, and 99.4% had type 1 diabetes, with a median duration of 4.3 years (SD 3.9). The median duration of DIYAPS use was 7.5 (SD 10.0) months. Clinical outcomes improved significantly, including the hemoglobin A1c levels (from 6.91% [SD 0.88%] to 6.27% [SD 0.67]; P<.001) and TIR (from 64.2% [SD 15.94] to 80.68% [SD 9.26]; P<.001). CONCLUSIONS: Improved glycemic outcomes were found across all pediatric age groups, including adolescents and very young children. These findings are in line with clinical trial results from commercially developed closed-loop systems.

Diabetes Technology: Monitoring, Analytics, and Optimal Control.

Over the past 50 years, the diabetes technology field progressed remarkably through self-monitoring of blood glucose (SMBG), continuous subcutaneous insulin infusion (CSII), risk and variability analysis, mathematical models and computer simulation of the human metabolic system, real-time continuous glucose monitoring (CGM), and control algorithms driving closed-loop control systems known as the "artificial pancreas" (AP). This review follows these developments, beginning with an overview of the functioning of the human metabolic system in health and in diabetes and of its detailed quantitative network modeling. The review continues with a brief account of the first AP studies that used intravenous glucose monitoring and insulin infusion, and with notes about CSII and CGM-the technologies that made possible the development of contemporary AP systems. In conclusion, engineering lessons learned from AP research, and the clinical need for AP systems to prove their safety and efficacy in large-scale clinical trials, are outlined.

The challenges of achieving postprandial glucose control using closed-loop systems in patients with type 1 diabetes.

For patients with type 1 diabetes, closed-loop delivery systems (CLS) combining an insulin pump, a glucose sensor and a dosing algorithm allowing a dynamic hormonal infusion have been shown to improve glucose control when compared with conventional therapy. Yet, reducing glucose excursion and simplification of prandial insulin doses remain a challenge. The objective of this literature review is to examine current meal-time strategies in the context of automated delivery systems in adults and children with type 1 diabetes. Current challenges and considerations for post-meal glucose control will also be discussed. Despite promising results with meal detection, the fully automated CLS has yet failed to provide comparable glucose control to CLS with carbohydrate-matched bolus in the post-meal period. The latter strategy has been efficient in controlling post-meal glucose using different algorithms and in various settings, but at the cost of a meal carbohydrate counting burden for patients. Further improvements in meal detection algorithms or simplified meal-priming boluses may represent interesting avenues. The greatest challenges remain in regards to the pharmacokinetic and dynamic profiles of available rapid insulins as well as sensor accuracy and lag-time. New and upcoming faster acting insulins could provide important benefits. Multi-hormone CLS (eg, dual-hormone combining insulin with glucagon or pramlintide) and adjunctive therapy (eg, GLP-1 and SGLT2 inhibitors) also represent promising options. Meal glucose control with the artificial pancreas remains an important challenge for which the optimal strategy is still to be determined.

Moving Toward a Unified Platform for Insulin Delivery and Sensing of Inputs Relevant to an Artificial Pancreas.

Advances in insulin pump and continuous glucose monitoring technology have primarily focused on optimizing glycemic control for people with type 1 diabetes. There remains a need to identify ways to minimize the physical burden of this technology. A unified platform with closely positioned or colocalized interstitial fluid glucose sensing and hormone delivery components is a potential solution. Present challenges to combining these components are interference of glucose sensing from proximate insulin delivery and the large discrepancy between the life span of current insulin infusion sets and glucose sensors. Addressing these concerns is of importance given that the future physical burden of this technology is likely to be even greater with the ongoing development of the artificial pancreas, potentially incorporating multiple hormone delivery, glucose sensing redundancy, and sensing of other clinically relevant nonglucose biochemical inputs.

Empowered citizen 'health hackers' who are not waiting.

Due to the easier access to information, the availability of low cost technologies and the involvement of well educated, passionate patients, a group of citizen 'Health Hackers', who are building their own medical systems to help them overcome the unmet needs of their conditions, is emerging. This has recently been the case in the type 1 diabetes community, under the movement #WeAreNotWaiting, with innovative use of current medical devices hacked to access data and Open-Source code producing solutions ranging from remote monitoring of diabetic children to producing an Artificial Pancreas System to automate the management and monitoring of a patient's condition. Timothy Omer is working with the community to utilise the technology already in his pocket to build a mobile- and smartwatch-based Artificial Pancreas System.