Summary Background Closed-loop systems link continuous glucose measurements to insulin delivery. We aimed to establish whether closed-loop insulin delivery could control overnight blood glucose in ...young people. Methods We undertook three randomised crossover studies in 19 patients aged 5–18 years with type 1 diabetes of duration 6·4 years (SD 4·0). We compared standard continuous subcutaneous insulin infusion and closed-loop delivery (n=13; APCam01); closed-loop delivery after rapidly and slowly absorbed meals (n=7; APCam02); and closed-loop delivery and standard treatment after exercise (n=10; APCam03). Allocation was by computer-generated random code. Participants were masked to plasma and sensor glucose. In APCam01, investigators were masked to plasma glucose. During closed-loop nights, glucose measurements were fed every 15 min into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. During control nights, patients' standard pump settings were applied. Primary outcomes were time for which plasma glucose concentration was 3·91–8·00 mmol/L or 3·90 mmol/L or lower. Analysis was per protocol. This trial is registered, number ISRCTN18155883. Findings 17 patients were studied for 33 closed-loop and 21 continuous infusion nights. Primary outcomes did not differ significantly between treatment groups in APCam01 (12 analysed; target range, median 52% IQR 43–83 closed loop vs 39% 15–51 standard treatment, p=0·06; ≤3·90 mmol/L, 1% 0–7 vs 2% 0–41, p=0·13), APCam02 (six analysed; target range, rapidly 53% 48–57 vs slowly absorbed meal 55% 37–64, p=0·97; ≤3·90 mmol/L, 0% 0–4 vs 0% 0–0, p=0·16), and APCam03 (nine analysed; target range 78% 60–92 closed loop vs 43% 25–65 control, p=0·0245, not significant at corrected level; ≤3·90 mmol/L, 10% 2–15 vs 6% 0–44, p=0·27). A secondary analysis of pooled data documented increased time in the target range (60% 51–88 vs 40% 18–61; p=0·0022) and reduced time for which glucose concentrations were 3·90 mmol/L or lower (2·1% (0·0–10·0) vs 4·1% (0·0–42·0); p=0·0304). No events with plasma glucose concentration lower than 3·0 mmol/L were recorded during closed-loop delivery, compared with nine events during standard treatment. Interpretation Closed-loop systems could reduce risk of nocturnal hypoglycaemia in children and adolescents with type 1 diabetes. Funding Juvenile Diabetes Research Foundation; European Foundation for Study of Diabetes; Medical Research Council Centre for Obesity and Related Metabolic Diseases; National Institute for Health Research Cambridge Biomedical Research Centre.
Closed-loop insulin delivery is a promising option to improve glycaemic control and reduce the risk of hypoglycaemia. We aimed to assess whether overnight home use of automated closed-loop insulin ...delivery would improve glucose control.
We did this open-label, multicentre, randomised controlled, crossover study between Dec 1, 2012, and Dec 23, 2014, recruiting patients from three centres in the UK. Patients aged 18 years or older with type 1 diabetes were randomly assigned to receive 4 weeks of overnight closed-loop insulin delivery (using a model-predictive control algorithm to direct insulin delivery), then 4 weeks of insulin pump therapy (in which participants used real-time display of continuous glucose monitoring independent of their pumps as control), or vice versa. Allocation to initial treatment group was by computer-generated permuted block randomisation. Each treatment period was separated by a 3–4 week washout period. The primary outcome was time spent in the target glucose range of 3·9–8·0 mmol/L between 0000 h and 0700 h. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01440140.
We randomly assigned 25 participants to initial treatment in either the closed-loop group or the control group, patients were later crossed over into the other group; one patient from the closed-loop group withdrew consent after randomisation, and data for 24 patients were analysed. Closed loop was used over a median of 8·3 h (IQR 6·0–9·6) on 555 (86%) of 644 nights. The proportion of time when overnight glucose was in target range was significantly higher during the closed-loop period compared to during the control period (mean difference between groups 13·5%, 95% CI 7·3–19·7; p=0·0002). We noted no severe hypoglycaemic episodes during the control period compared with two episodes during the closed-loop period; these episodes were not related to closed-loop algorithm instructions.
Unsupervised overnight closed-loop insulin delivery at home is feasible and could improve glucose control in adults with type 1 diabetes.
Diabetes UK.
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