Home use of closed-loop insulin delivery for overnight glucose control in adults with type 1 diabetes: a 4-week, multicentre, randomised crossover study

Abstract

Background: 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.

Methods: 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.

Findings: 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.

Interpretation: Unsupervised overnight closed-loop insulin delivery at home is feasible and could improve glucose control in adults with type 1 diabetes.

Funding: Diabetes UK.

Figure 1

Study design comparing overnight closed loop insulin delivery with control. The outline shows when continuous glucose monitoring data were collected, efficacy assessed, and adverse events monitored.

Figure 2

Flow of participants through the trial.

Figure 3

Median (interquartile range) of sensor glucose (top panel) and insulin delivery (bottom panel) during closed loop (solid red line and red shaded area) and control (dashed black line and gray shaded area) period for the 24-hour duration. The glucose range 3·9 to 8·0 mmol/l is denoted in the top panel by horizontal dashed lines.

Figure 4

Individual values of time when glucose was in target glucose range from 3·9 to 8·0 mmol/l (left panel) and mean overnight glucose (right panel) (n=24).