Hybrid closed-loop insulin therapy may reduce the risk of severe hypoglycemic coma but may still be linked to an increased incidence of diabetic ketoacidosis in pediatric and adolescent patients with type 1 diabetes, a new comprehensive population-based study shows.
In the study, published in The Lancet Diabetes & Endocrinology, investigators evaluated data from over 17,000 patients aged 1 to 21 years, collected from national diabetes registries across multiple countries between 2018 and 2023.
They compared patients using hybrid closed-loop (HCL) systems, which automatically adjust insulin delivery based on continuous glucose monitoring, with those using standard insulin pump therapy. The results showed that patients using HCL therapy experienced a 38% lower risk of severe hypoglycemic coma (adjusted hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.50–0.76, P < .001). This reduction underscored the effectiveness of HCL systems in preventing acute hypoglycemic complications. However, the incidence of diabetic ketoacidosis was 1.4 times higher in the HCL group (adjusted HR = 1.41, 95% CI = 1.20–1.67, P < .001), indicating a trade-off between improved glycemic control and elevated risk of hyperglycemic crises.
HCL therapy users also achieved better glycemic control, reflected by a mean reduction of 0.5% in HbA1c levels (P < .001) and a 12% improvement in time-in-range glucose levels. The findings highlighted enhanced day-to-day glucose stability for users of the HCL system. However, pharmacovigilance data revealed that interruptions in insulin delivery as a result of technical issues contributed significantly to diabetic ketoacidosis episodes among HCL users. The investigators emphasized the need for proper device management, robust user training, and emergency protocols to mitigate these risks.
"[HCL] insulin delivery has no significant effect on the rate of severe hypoglycemia and is associated with an increased risk of diabetic ketoacidosis, but is associated with a reduced risk of hypoglycemic coma and improved glycemia," said lead study author Beate Karges, MD, of the Division of Endocrinology and Diabetes at the RWTH Aachen University in Germany, and colleagues.
The study’s strengths included its large sample size, diverse multinational data sources, and real-world applicability. However, limitations such as the observational design and absence of randomized control trials necessitated cautious interpretation of causal relationships. The investigators called for further randomized clinical trials to validate these findings and explore strategies to reduce diabetic ketoacidosis risk while maintaining the glycemic benefits of HCL systems.
Future research should focus on refining HCL algorithms, enhancing device reliability, and developing comprehensive training programs in patients and caregivers. By addressing these areas, health care providers can maximize the safety and effectiveness of these technologies in young patients with type 1 diabetes.
The authors reported no competing interests, and all research protocols adhered to ethical guidelines across all participating centers.
