Closed-loop insulin delivery systems in children and adolescents with type 1 diabetes

ABSTRACT

Introduction: Optimal glycemic control remains challenging in children and adolescents with type 1 diabetes due to highly variable day-to-day and night-to-night insulin requirements. This hurdle could be addressed by glucose-responsive insulin delivery based on real-time continuous glucose measurements.

Areas covered: This review summaries recent advances of closed-loop systems in children and adolescents with type 1 diabetes, using both single- and dual-hormone closed-loop systems. The main outcomes, proportions of time spent in target range 70–180 mg/dl, and time spent in hypoglycemia below 70 mg/dl, are assessed particularly during unsupervised free-living randomized controlled trials.

Expert opinion: Noteworthy and clinically meaningful translation of experimental investigations from controlled in-hospital settings to unrestricted home studies have been achieved over the past years, resulting in the regulatory approval of the first hybrid closed-loop system also in the pediatric population and with several other advanced devices in the pipeline. Large multinational and pivotal clinical trials including broad age populations are underway to facilitate the use of closed-loop systems in routine clinical practice.

KEYWORDS:

• Artificial pancreas
• type 1 diabetes
• continuous glucose monitoring
• children
• technology
• closed-loop

Article highlights

• Despite the developments in insulin therapy, optimal glycemic control remains unachievable for many children and adolescents with type 1 diabetes due to highly variable insulin requirements and might be difficult to overcome with conventional insulin therapy.

• Closed-loop safely and significantly improves glycemic control, increases time in range, and reduces hypoglycemia in a broad range of pediatric populations with type 1 diabetes included in clinical trials.

• Hybrid closed-loop insulin therapy is now a routine clinical reality for many individuals with type 1 diabetes aged 7 years and older.

• Continuous technical improvements of closed-loop systems will further improve safety and efficacy, likely through the development of open-frame, personalized, cloud-based ecosystems.

This box summarizes the key points contained in the article.

Declaration of interest

T. Battelino has received honoraria for participation on advisory boards for Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer, Medtronic, and Bayer Health Care and as a speaker for AstraZeneca, Eli Lilly and Company, Bayer, Novo Nordisk, Medtronic, Sanofi, and Roche. T. Battelino owns stocks of DreaMed Diabetes, and his institution has received research grant support and travel expenses from Abbott Diabetes Care, Medtronic, Novo Nordisk, Glu-Sense, Sanofi, Sandoz, and Diamyd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed grant support, consulting fees, and speakers bureau fees from Tandem Diabetes Care; grant support from Medtronic; grant support and consulting fees from Eli Lilly; grant support and supplies from Insulet; and supplies from Dexcom. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

The study was funded in part by the University Medical Centre Ljubljana Research and Development Grant no. 20110359. KD and TB were funded in part by the Slovenian National Research Agency Grants no. J3–6798, V3–1505 and P3–0343.