Managing blood glucose in individuals with type 1 diabetes (T1D) is a significant clinical challenge. Insulin therapy, which typically involves insulin injections or the use of insulin pumps, aims to mimic the body's natural insulin production. Over recent years, hybrid closed-loop insulin systems, which integrate continuous glucose monitoring (CGM) with insulin pumps, have been developed to automatically adjust insulin delivery. These systems are designed to improve blood glucose control, but their impact on the risk of severe hypoglycaemia and diabetic ketoacidosis (DKA) remains uncertain. A recent study published in The Lancet: Diabetes & Endocrinology investigates whether hybrid closed-loop insulin therapy can reduce the risk of these serious complications compared to traditional open-loop insulin pump therapy in young people aged 2 to 20 years.
Study Design and Population
This population-based cohort study analysed data from 13,922 young individuals with type 1 diabetes, aged 2 to 20 years, who were treated at 250 diabetes centres across Germany, Austria, Switzerland and Luxembourg. The participants had been using either hybrid closed-loop insulin therapy or open-loop pump therapy for at least 120 days. The study aimed to compare the rates of severe hypoglycaemia and DKA between the two treatment groups, as well as secondary outcomes related to glycaemic control, such as HbA1c levels, time in glucose range and glycaemic variability. The study utilised propensity score inverse probability weighting to account for confounders, such as age, baseline HbA1c and diabetes duration, which could influence treatment choice.
Hypoglycaemia and Diabetic Ketoacidosis Rates
The results of the study revealed no significant difference in the overall rate of severe hypoglycaemia between the two groups. The closed-loop therapy group had a rate of 5.59 severe hypoglycaemia events per 100 patient-years, compared to 6.63 per 100 patient-years in the open-loop group. This suggests that hybrid closed-loop therapy does not offer a major advantage in reducing severe hypoglycaemia compared to open-loop therapy. However, when examining the incidence of hypoglycaemic coma—an extreme form of hypoglycaemia that requires external assistance—hybrid closed-loop therapy demonstrated a significantly lower rate (0.62 per 100 patient-years) compared to open-loop therapy (0.91 per 100 patient-years). This finding suggests that closed-loop systems may be effective in preventing the progression of mild hypoglycaemia to more severe forms.
Conversely, the study found a significantly higher risk of DKA in the hybrid closed-loop therapy group. The rate of DKA was 1.74 per 100 patient-years in the closed-loop group, compared to 0.96 per 100 patient-years in the open-loop group. This represents a substantial increase in the risk of DKA for those using the hybrid system. The risk was particularly high among individuals with higher HbA1c levels, with those in the closed-loop group showing a DKA rate of 5.25 per 100 patient-years for those with HbA1c levels above 8.5%, compared to just 1.53 per 100 patient-years in the open-loop group. This suggests that hybrid closed-loop therapy may not be as effective at preventing DKA in individuals with poor glycaemic control.
Glycaemic Control and Other Key Findings
Despite the higher risk of DKA, hybrid closed-loop therapy led to notable improvements in glycaemic control. The closed-loop group had a lower median HbA1c (7.34%) compared to the open-loop group (7.50%), a difference that is clinically relevant. Additionally, the closed-loop group spent a higher percentage of time within the target glucose range (3.9–10.0 mmol/L), with 64% of their time in the range compared to 52% in the open-loop group. This 12% improvement in time spent within the target range is a significant benefit, as maintaining glucose within this range is associated with better long-term health outcomes and a lower risk of diabetes-related complications. Furthermore, the closed-loop group had less glycaemic variability, which is the degree of fluctuation in blood glucose levels. The coefficient of variation in the closed-loop group was 35.4%, compared to 38.3% in the open-loop group, indicating that the hybrid system provides more stable blood glucose control.
These improvements in glycaemic control are consistent with previous studies of hybrid closed-loop therapy, which have shown that it can help reduce HbA1c levels and improve time in range. The ability of closed-loop systems to dynamically adjust insulin delivery based on real-time glucose readings likely plays a key role in reducing glycaemic variability and improving control. These findings suggest that hybrid closed-loop therapy is an effective tool for improving diabetes management in young people with T1D, particularly for those who are struggling to maintain optimal blood glucose levels with open-loop therapy.
This large-scale, population-based study provides valuable insights into the use of hybrid closed-loop insulin therapy in young people with type 1 diabetes. While the therapy did not significantly reduce the overall risk of severe hypoglycaemia, it was associated with a lower rate of hypoglycaemic coma. Additionally, it improved glycaemic control, with better HbA1c levels, more time in the target glucose range and reduced glycaemic variability. However, the study also highlighted an increased risk of diabetic ketoacidosis, particularly in those with higher HbA1c levels, suggesting that hybrid closed-loop therapy may not be as effective at preventing DKA in individuals with suboptimal glycaemic control.
These findings emphasise the importance of closely monitoring patients on hybrid closed-loop therapy, particularly those with poor glycaemic control, to mitigate the risk of DKA. Educational measures for patients and caregivers are essential to ensure proper management of the system and prevent complications. While hybrid closed-loop insulin therapy offers clear benefits in terms of glycaemic control, further research is needed to better understand the mechanisms behind the increased risk of DKA and explore ways to refine the technology and its use.
Source: The Lancet: Diabetes & Endocrinology
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