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.

Changing costs of type 1 diabetes care among US children and adolescents.

BACKGROUND: Modern therapy for type 1 diabetes (T1D) increasingly utilizes technology such as insulin pumps and continuous glucose monitors (CGMs). Prior analyses suggest that T1D costs are driven by preventable hospitalizations, but recent escalations in insulin prices and use of technology may have changed the cost landscape. METHODS: We conducted a retrospective analysis of T1D medical costs from 2012 to 2016 using the OptumLabs Data Warehouse, a comprehensive database of deidentified administrative claims for commercial insurance enrollees. Our study population included 9445 individuals aged ≤18 years with T1D and ≥13 months of continuous enrollment. Costs were categorized into ambulatory care, hospital care, insulin, diabetes technology, and diabetes supplies. Mean costs for each category in each year were adjusted for inflation, as well as patient-level covariates including age, sex, race, census region, and mental health comorbidity. RESULTS: Mean annual cost of T1D care increased from $11 178 in 2012 to $17 060 in 2016, driven primarily by growth in the cost of insulin ($3285 to $6255) and cost of diabetes technology ($1747 to $4581). CONCLUSIONS: Our findings suggest that the cost of T1D care is now driven by mounting insulin prices and growing utilization and cost of diabetes technology. Given the positive effects of pumps and CGMs on T1D health outcomes, it is possible that short-term costs are offset by future savings. Long-term cost-effectiveness analyses should be undertaken to inform providers, payers, and policy-makers about how to support optimal T1D care in an era of increasing reliance on therapeutic technology.

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.

Use of Diabetes Technology in Children: Role of Structured Education for Young People with Diabetes and Families.

The current era has witnessed an explosion of advanced diabetes technologies. Young people with diabetes and their families require detailed, structured diabetes education in order to optimize use of such devices. There is need for youth and their families to participate in the selection of particular devices for personal use and comprehensive education regarding the safe and effective use of such technologies. The education process should ensure that youth and their families receive realistic expectations of what the advanced technologies can and cannot do to avoid disappointment and the premature discontinuation of such systems.

Diabetes Technology Use in Adults with Type 1 and Type 2 Diabetes.

In the last 2 decades, diabetes technology has emerged as a branch of diabetes management thanks to the advent of continuous glucose monitoring (CGM) and increased availability of continuous subcutaneous insulin infusion systems, or insulin pumps. These tools have progressed from rudimentary instruments to sophisticated therapeutic options for advanced diabetes management. This article discusses the available CGM and insulin pump systems and the clinical benefits of their use in adults with type 1 diabetes, intensively insulin-treated type 2 diabetes, and pregnant patients with preexisting diabetes.

Benefits and Challenges of Diabetes Technology Use in Older Adults.

With successful aging of adults with type 1 diabetes, there is an increased opportunity to use technology for diabetes management. Technology can ease the burden of self-care and provide a sense of security. However, age-related cognitive and physical decline can make technology use difficult. Guidelines using technology in the aging population are urgently needed, along with educational material for the clinicians and caregivers. In this article, we review the evidence supporting the use of diabetes-related technologies in the older population and discuss recommendations based on current data and the authors' clinical knowledge and experience.

Integration of Diabetes Technology in Clinical Practice.

This article attempts to aid clinicians in using diabetes devices in their clinical practice. It reviews device selection, initiation, and follow-up. It discusses work flow in an office and provides tips on billing. It stresses the need for patient choice, education, and on-going support through downloading and interpretation of data to optimize care.

Diabetes Technology in the Inpatient Setting for Management of Hyperglycemia.

In past decades, a rapid evolution of diabetes technology led to increased popularity and use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) in the ambulatory setting for diabetes management, and recently, the artificial pancreas became available. Efforts to translate this technology to the hospital setting have shown accuracy and reliability of CGM, safety of CSII in appropriate populations, improvement of inpatient glycemic control with computerized glycemic management systems, and feasibility of inpatient CGM-CSII closed-loop systems. Several ongoing studies are focusing on continued translation of this technology to improve glycemic control and outcomes in hospitalized patients.

Psychosocial aspects of diabetes technology.

AIM: To identify key psychosocial research in the domain of diabetes technology. RESULTS: Four trajectories of psychosocial diabetes technology research are identified that characterize research over the past 25 years. Key evidence is reviewed on psychosocial outcomes of technology use as well as psychosocial barriers and facilitating conditions of diabetes technology uptake. Psychosocial interventions that address modifiable barriers and psychosocial factors have proven to be effective in improving glycaemic and self-reported outcomes in diabetes technology users. CONCLUSIONS: Psychosocial diabetes technology research is essential for designing interventions and education programmes targeting the person with diabetes to facilitate optimized outcomes associated with technology uptake. Psychosocial aspects of diabetes technology use and related research will be even more important in the future given the advent of systems for automated insulin delivery and the increasingly widespread digitalization of diabetes care.

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.

Patch Pumps: Are They All the Same?

Insulin pumps are used by a steadily increasing number of patients with diabetes. Avoiding certain disadvantages of conventional pumps (ie, the insulin infusion set) might make pump therapy even more attractive. Patch pumps are usually attached by means of an adhesive layer to the skin and have several additional advantages (smaller, more discrete, easier to use, and cheaper than conventional insulin pumps). This review provides a general overview of patch pumps, the technologies used, basic clinical requirements, why a number of developments failed, which clinical studies are needed to provide sufficient evidence for their usage, which costs are associated, what the patient preferences are (which might differ between certain patient groups), and what is the future of patch pumps (ie, artificial pancreas systems).

Continuous Glucose Monitoring, Future Products, and Update on Worldwide Artificial Pancreas Projects.

The development of accurate and easy-to-use continuous glucose monitoring (CGM) improved diabetes treatment by providing additional temporal information on glycemia and glucose trends to patient and physician. Although CGM enables users to lower their average glucose level without an increased incidence of hypoglycemia, this comes at the price of additional patient effort. Automation of insulin administration, also known as closed-loop (CL) or artificial pancreas treatment, has the promise to reduce patient effort and improve glycemic control. CGM data serve as the conditional input for insulin automation devices. The first commercial product for partial automation of insulin administration used insulin delivery shutoff at a predefined glucose level. These systems showed a reduction in hypoglycemia. Insulin-only CL devices show increased time spent in euglycemia and a reduction of hypo- and hyperglycemia. Improved glycemic control, coinciding with a minor decrease in hemoglobin A1c level, was confirmed in recent long-term home studies investigating these devices, paving the way for pivotal studies for commercialization of the artificial pancreas. Although the first results from dual-hormone CL systems are promising, because of increased cost of consumables of these systems, long-term head-to-head studies will have to prove superiority over insulin-only approaches. Now CL glucose control for daily use might finally become reality. Improved continuous glucose sensing technology, miniaturization of electrical devices, and development of algorithms were key in making this possible. Clinical adoption challenges, including device usability and reimbursement, need to be addressed. Time will tell for which patient groups CL systems will be reimbursed and whether these devices can deliver the promise that they hold.

Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics.

The level of glycaemic control necessary to achieve optimal short-term and long-term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid-acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health-related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid-acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost-effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid-acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients' health-related quality of life; reviews relevant pharmacoeconomic data; and discusses recent advances in pump technology, including the development of closed-loop 'artificial pancreas' systems. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.

Pathway to artificial pancreas systems revisited: moving downstream.

Artificial pancreas (AP) systems, a long-sought quest to replicate mechanically islet physiology that is lost in diabetes, are reaching the clinic, and the potential of automating insulin delivery is about to be realized. Significant progress has been made, and the safety and feasibility of AP systems have been demonstrated in the clinical research center and more recently in outpatient "real-world" environments. An iterative road map to AP system development has guided AP research since 2009, but progress in the field indicates that it needs updating. While it is now clear that AP systems are technically feasible, it remains much less certain that they will be widely adopted by clinicians and patients. Ultimately, the true success of AP systems will be defined by successful integration into the diabetes health care system and by the ultimate metric: improved diabetes outcomes.

Banting Memorial Lecture 2014* Technology and diabetes care: appropriate and personalized.

Continuous subcutaneous insulin infusion was initially developed as a research procedure in the 1970s but quickly became a routine treatment for selected people with Type 1 diabetes. Continuous subcutaneous insulin infusion and other diabetes technologies, such as continuous glucose monitoring, are now an established and evidence-based part of diabetes care, but there has been some confusion about effectiveness and best use, particularly because of conflicting results from meta-analyses. This is because literature summary meta-analyses (including all trials) are inappropriate for therapeutic and economic decision-making; such meta-analyses should only include trials representative of groups likely to benefit. For example, for continuous subcutaneous insulin infusion, this would be those with continued disabling hypoglycaemia or elevated HbA1c levels. Alternatively, individual patient data meta-analysis allows modelling of covariates that determine effect size, e.g. in the case of continuous glucose monitoring, baseline HbA1c and frequency of sensor usage. Diabetes technology is therefore an example of personalized medicine, where evaluation and use should be both appropriate and targeted. This will also apply to future technologies such as new 'patch' pumps for Type 2 diabetes, closed-loop insulin delivery systems and nanomedicine applications in diabetes that we are currently researching. These include fluorescence lifetime-based non-invasive glucose monitoring and nanoencapsulation of islets for improved post-transplant survival.

Artificial pancreas: an emerging approach to treat Type 1 diabetes.

Intensive insulin therapy aimed at achieving normal glucose levels significantly reduces the complications that are associated with diabetes but is also associated with an increased risk of low glucose levels (hypoglycemia). The growing use of continuous glucose monitors has stimulated the development of the artificial pancreas, a closed-loop insulin-delivery system aimed at restoring near-normal glucose levels while reducing the risk of hypoglycemia. The artificial pancreas comprises three components: a continuous glucose monitor, an insulin infusion pump and a control algorithm delivering insulin according to real-time glucose readings. In this article, we review closed-loop glucose control, including its components, development, testing and clinical application.