Hybrid closed-loop insulin therapy and risk of severe hypoglycaemia and diabetic ketoacidosis in young people (aged 2-20 years) with type 1 diabetes: a population-based study

Background: The effect of closed-loop insulin delivery on the risk of acute diabetes complications in people with type 1 diabetes is unclear. We investigated whether the rates of severe hypoglycaemia and diabetic ketoacidosis are lower with hybrid closed-loop insulin therapy compared with sensor-augmented (open-loop) pump therapy in a large cohort of young people.

Methods: In this population-based cohort study, we evaluated young people with type 1 diabetes from 250 diabetes centres in Germany, Austria, Switzerland, and Luxembourg participating in the Diabetes Prospective Follow-up (DPV) initiative. Included participants were aged 2-20 years, with diabetes duration of more than 1 year, and were treated between Jan 1, 2021, and Dec 31, 2023. The primary outcomes were the rates of severe hypoglycaemia and ketoacidosis in people using closed-loop therapy versus open-loop therapy. Key secondary outcomes were differences in HbA_1c levels, percentage of time in glucose range of 3·9-10·0 mmol/L, and glycaemic variability. To account for relevant confounders, we applied propensity score inverse probability of treatment weighting considering several baseline characteristics.

Findings: 13 922 young people (median age 13·2 years [IQR 10·0 to 16·0]; 51% male) in the DPV database met inclusion criteria and were included in the analysis. 7088 used closed-loop therapy and 6834 used open-loop therapy, with a median observation time of 1·6 years [IQR 1·1 to 2·4]. Individuals using closed-loop therapy had a higher rate of ketoacidosis (1·74 per 100 patient-years) than those using open-loop therapy (0·96 per 100 patient-years; incidence rate ratio 1·81 [1·37 to 2·40], p<0·0001) and there was no significant difference between groups in the rate of severe hypoglycaemia (5·59 per 100 patient-years vs 6·63 per 100 patient-years; incidence rate ratio 0·84 [95% CI 0·69 to 1·03], p=0·089). Individuals using closed-loop therapy had a lower rate of hypoglycaemic coma (0·62 per 100 patient-years) compared with individuals using open-loop therapy (0·91 per 100 patient-years; incidence rate ratio 0·68 [95% CI 0·48 to 0·97], p=0·034). Those in the closed-loop therapy group also had a lower HbA_1c level (7·34% vs 7·50%; difference -0·16% [95% CI -0·20 to -0·13], p=0·0007), higher percentage of time in target glucose range of 3·9-10·0 mmol/L (64% vs 52%, difference 12% [10 to 14], p<0·0001), and less glycaemic variability (coefficient of variation 35·4% vs 38·3%; difference -2·9% [-3·3 to -2·5], p<0·0001) than those in the open-loop therapy group. The rate of ketoacidosis was particularly high in young people with HbA_1c of 8·5% or higher in the closed-loop therapy group (5·25 per 100 patient-years) compared with the open-loop therapy group (1·53 per 100 patient-years; incidence rate ratio 3·43 [95% CI 1·69 to 6·97], p<0·0001).

Interpretation: Hybrid closed-loop insulin delivery has no significant effect on the rate of severe hypoglycaemia, and is associated with an increased risk of diabetic ketoacidosis, but is associated with a reduced risk of hypoglycaemic coma and improved glycaemia. These findings indicate the need for additional educational measures for the use of closed-loop insulin delivery.

Funding: German Center for Diabetes Research, German Diabetes Society, and Robert Koch Institute.