Long-term assessment of the NHS hybrid closed-loop real-world study on glycaemic outcomes, time-in-range, and quality of life in children and young people with type 1 diabetes

In the UK, there is a scarcity of real-world published data on the utilisation of hybrid closed-loop (HCL) systems within the paediatric population.

The NHS England Closed Loop Study in Children and Young People represents a ground-breaking initiative, marking the first nationwide pilot effort to extend universal health coverage for HCL systems. This study stands out as the largest real-world investigation of HCL in the UK, revealing a sustained enhancement in glycaemic management, time-in-range, and quality of life measures. These improvements encompass reduced fear and worry related to hypoglycaemia, as well as enhanced sleep quality for both patients and their caregivers, observed 6 and 12 months post-HCL adoption.

This study signals the need for future investigations to delve into the extended impact of HCL in this population over a more prolonged duration. Additionally, it highlights the importance of including hard-to-reach and diverse groups in subsequent research endeavours, ensuring a comprehensive understanding of the potential benefits and challenges associated with HCL systems in paediatric care.

Type 1 diabetes (T1DM) is a chronic condition that requires vigilant management of blood glucose concentrations to prevent both short-term complications, such as hypoglycaemia, and long-term complications, such as cardiovascular disease and kidney failure. Children and young people (CYP) with T1DM face unique challenges, as managing their blood glucose concentrations involves a delicate balance between insulin administration, diet, and physical activity [1]. In recent years, there has been a significant breakthrough in diabetes care with the introduction of hybrid closed-loop systems, offering a promising solution for achieving better blood glucose management while reducing the risk of hypoglycaemia in paediatric patients.

A hybrid closed-loop system (HCL) is an advanced diabetes management technology that automates the delivery of insulin based on real-time continuous glucose monitoring (CGM) [2]. These innovative system aims to bridge the gap between traditional insulin pumps and CGMs, providing a more seamless and dynamic approach to diabetes care. In children and adults with T1D, this technology has demonstrated potential in improving overall glycaemic management and minimising the blood glucose fluctuations that often lead to hypoglycaemic episodes as well as reducing fear of hypoglycaemia [3, 4]. The core components of a hybrid closed-loop system include a subcutaneous CGM, an insulin pump, and a control algorithm. The CGM continuously measures glucose levels in the interstitial fluid, providing real-time data to the pump algorithm. The algorithm then processes this information and adjusts insulin delivery rates accordingly. This closed-loop approach allows for timely and precise insulin adjustments, reducing the reliance on manual interventions from caregivers or the child [5, 6].

In the UK, the National Health Service England (NHSE) commenced a pilot initiative of HCL in CYP across eight paediatric centres. The NHSE Closed Loop Study represents a ground-breaking initiative, marking the first nationwide pilot effort to extend universal health coverage for HCL systems This study reports on the 12-month follow-up of real-world data related to glycaemic management, time-in-range measures, and quality of life impact for CYP and their carers and extends our previously published short-term impact study [7].

A total of 251 CYP with T1D were recruited, comprising 147 males (58%). The mean age at recruitment was 12.3 years (SD 3.5), ranging from 2 to 19 years. The majority (89%) were of white ethnicity, with 3% Asian, 4% black, and 3% mixed ethnicity. A slight deviation from the 2019 Office for National Statistics estimate was noted, with more individuals from white and fewer from Asian ethnicities. The overall mean duration of diabetes was 6.6 years (SD 3.7), ranging from 1.0 to 15.7 years. The male-to-female ratio was 1.4:1, higher than the typically equal sex ratio for CYP with T1D. Demographic variations between the eight participating centres are detailed in Table 1, with notable distinctions in gender distribution and ethnic makeup in specific centres.

Significant improvements were observed in HbA1c, TIR, and frequency of hypoglycaemia after 3, 6, and 12 months of HCL use compared to 3 months prior to starting HCL. HbA1c decreased from 62 (SD 11) mmol/mol at the start to 55 (SD 9) mmol/mol at 6 months and was sustained at 55 (SD 11) mmol/mol at 12 months (p < 0.001) (Table 2). A linear relationship was noted between the initial HbA1c and the reduction after 6 and 12 months of HCL use. There was a significant linear relationship (Fig. 1) between the HbA1c at the start of HCL and the reduction after 12 months of HCL use described by the equation: Change in HbA1c at 12 months = -0.50 (Pre HCl HbA1c) + 24.3, r = 0.60; p < 0.001 (Fig. 1). Using the Oldham approach to testing for regression to the mean a linear relationship between change in HbA1c at 12 months and average of pre- and 12-month HbA1c was observed (r =  − 0.21; p = 0.001) excluding a regression to the mean as the main explanation for the change observed.

TIR increased to 63% (SD 12) at 6 months and was again sustained at 62.0% (SD 12) at 12 months (p < 0.001), while time spent with sensor glucose < 3.9 mmol/l decreased from 3.7% (SD 3.1) to 2.4% (SD 2.2) at 6 months and 2.0% (SD 1.6) at 12 months (p < 0.001). A threshold analysis using an HbA1c value of 48.6 mmol/mol (point on linear regression where change in HbA1c was zero) revealed a slight decrease in TIR over the 12-month period and a reduction in the percentage of time hypoglycaemic from 8% pre-HCL to 2.7% after 12 months of HCL use (P = 0.02). Fear of hypoglycaemia scores and sleep disturbance scores showed a significant reduction over the 12-month study period (p < 0.001) (Table 3). Notably, no differences were observed in biochemical, hypoglycaemia, and sleep score measures after 12 months among the different types of HCL used (Table 4).

The NHSE Closed Loop Study demonstrated notable and sustained improvements in various diabetes-related parameters over a 12-month period. These enhancements included better glycaemic management, increased TIR, reduced frequency of hypoglycaemia, diminished hypoglycaemia fear, and improved quality of sleep for CYP. These findings align with existing real-world data, suggesting the superiority of HCL systems in achieving target glucose range, preventing hypoglycaemia, and reducing glycaemic variability. The positive impact extended to parents and carers, who also experienced improved hypoglycaemia fear and sleep quality at 12 months. Notably, the observed changes in glycaemic measures, TIR, and hypoglycaemia frequency were consistent at 3, 6, and 12 months suggesting the absence of a Hawthorne effect during this period. The improvements in hypoglycaemia fear and sleep quality represent significant advancements, relieving individuals of the burdens associated with diabetes. To put the HbA1c data in perspective, the baseline HbA1c (62 mmol/mol) was similar to that recorded in the National Paediatric Diabetes Audit (NPDA) 2021/22 (61 mmol/mol) and was reduced by 7 mmol/mol during the course of the study whereas the NPDA value had remained unchanged over the previous audit year.

One of the primary advantages of HCL systems is their ability to maintain blood glucose concentrations within a target range more consistently [19, 20]. This is particularly crucial in children, as their glucose concentrations tend to fluctuate more rapidly due to factors such as growth, physical activity, and varying meal sizes. The HCL system adapts to these changes in real-time, leading to improved overall glycaemic management. Hypoglycaemia is a constant concern for caregivers of children with T1DM. The HCL system’s ability to detect and respond to falling tissue glucose concentrations helps prevent hypoglycaemic episodes. By providing precise insulin delivery adjustments, the system minimises the risk of overshooting and causing low blood glucose concentrations, a common concern with manual insulin administration.

Nocturnal hypoglycaemia is a significant concern for parents of CYP with T1DM. Hybrid closed-loop systems have demonstrated efficacy in maintaining stable overnight glucose concentrations, providing parents with greater peace of mind and ensuring that children can enjoy uninterrupted sleep. Numerous clinical trials have investigated the efficacy of HCL systems in CYP with T1DM, consistently showing positive outcomes [21, 22].

The landmark “International Diabetes Closed-Loop” (iDCL) trial, for instance, demonstrated that CYP using HCL systems experienced a significant reduction in time spent in hypoglycaemia compared to those using conventional pump therapy[23]. Additionally, a study published in the New England Journal of Medicine found that CYP aged 6 to 13 years using a HCL system achieved better glycaemic management and spent more time in the target glucose range compared to those using a traditional insulin pump [24]. These findings underscore the potential of HCL systems to revolutionise diabetes management in the CYP population [25]. While the benefits of HCL systems in paediatric diabetes care are evident, challenges and considerations remain. Issues such as system accuracy, device adherence, and the need for periodic sensor calibrations may pose practical challenges for some families. Moreover, the cost of these systems and the accessibility to the latest technology can be barriers for widespread adoption.

While the real-world study drew data from an unselected diabetes population, providing strength in its large and representative sample, the predominantly white population raises considerations about diversity as a limitation of the study. Another limitation was the intention to treat was not used as analyses as detailed information for dropout was not available within a real-world study. The linear relationship between the decrease in HbA1c during HCL use and the starting value, while accounting for regression to the mean, suggests potential benefits for individuals struggling with higher HbA1c values. Furthermore, the study implies that even patients with initially optimal HbA1c values can benefit further from HCL systems, particularly in terms of reducing time spent in hypoglycaemia which improved over the 12-month study period. The study was not constructed to determine whether any one HCL system was superior to another, so usage at present will be determined by the patient choice of the options available. The reduction in hypoglycaemia fear and improved sleep quality, likely attributed to reduced time spent with low tissue glucose, contribute to a decrease in overall diabetes burden. These positive outcomes were shown to be sustained and had a longer assessment period than many clinical trials that do not go beyond 6 months. It further underscores the potential role of HCL in managing diabetes in CYP, warranting further exploration of its cost-effectiveness and overall impact on diabetes burden.

Hybrid closed-loop systems represent a ground-breaking advancement in the management of T1DM in CYP, offering a more automated and responsive approach to insulin delivery. The evidence from clinical trials consistently supports the use of these systems in achieving better glycaemic management and reducing the risk of hypoglycaemia. This study demonstrates the sustained improvements over a 12-month period in a real-world setting which was comparable to other real-world studies[26]. As technology continues to evolve, addressing challenges related to accuracy, accessibility, and cost will be crucial in ensuring that these innovative solutions become standard paediatric diabetes care. Ultimately, the integration of HCL systems has the potential to transform the lives of CYP with T1DM, providing them with greater freedom, improved health outcomes, and a brighter future.