Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial

Abstract

Summary Background Glucose management is challenging in patients who require nutritional support in hospital. We aimed to assess whether fully closed-loop insulin delivery would improve glycaemic control compared with conventional subcutaneous insulin therapy in inpatients receiving enteral or parenteral nutrition or both. Methods We did a two-centre (UK and Switzerland), open-label, randomised controlled trial in adult inpatients receiving enteral or parenteral nutrition (or both) who required subcutaneous insulin therapy. Patients recruited from non-critical care surgical and medical wards were randomly assigned (1:1) using a computer-generated minimisation schedule (stratified by type of nutritional support [parenteral nutrition on or off] and pre-study total daily insulin dose [<50 or ≥50 units]) to receive fully closed-loop insulin delivery with faster-acting insulin aspart (closed-loop group) or conventional subcutaneous insulin therapy (control group) given in accordance with local clinical practice. Continuous glucose monitoring in the control group was masked to patients, ward staff, and investigators. Patients were followed up for a maximum of 15 days or until hospital discharge. The primary endpoint was the proportion of time that sensor glucose concentration was in target range (5·6–10·0 mmol/L), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT01774565 . Findings Between Feb 8, 2018, and Sept 21, 2018, 90 patients were assessed for eligibility, of whom 43 were enrolled and randomly assigned to the closed-loop group (n=21) or the control group (n=22). The proportion of time that sensor glucose was in the target range was 68·4% [SD 15·5] in the closed-loop group and 36·4% [26·6] in the control group (difference 32·0 percentage points [95% CI 18·5–45·5; p<0·0001]). One serious adverse event occurred in each group (one cardiac arrest in the control group and one episode of acute respiratory failure in the closed-loop group), both of which were unrelated to study interventions. There were no adverse events related to study interventions in either group. No episodes of severe hypoglycaemia or hyperglycaemia with ketonaemia occurred in either study group. Interpretation Closed-loop insulin delivery is an effective treatment option to improve glycaemic control in patients receiving nutritional support in hospital. Funding Diabetes UK, Swiss National Science Foundation, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust, and European Foundation for the Study of Diabetes.

Short‐term fully closed‐loop insulin delivery using faster insulin aspart compared with standard insulin aspart in type 2 diabetes

“…We aimed to analyze 15 participants with complete data. The primary endpoint was the percentage of time with plasma glucose between 5.6 to 10.0 mmol/L from 07:00 to 17:00 (10 hours), in line with previous studies in adults with type 2 diabetes using the same fully closed‐loop insulin delivery system . Other endpoints are listed in Table S1.…”

Safe care for people with diabetes in hospital

“…53,54 The use of closed looped systems in inpatients is a technology currently under development and has shown some promising results. 55,56 There are also data to show that education in insulin prescribing reduces insulin errors. 57 Whether electronic records and electronic prescribing will make a difference to the incidence and prevalence of prescribing errors remains to be seen.…”

Glycaemic control on nutritional support: finding stability in unstable times

“…system, and costs of and work needed for integration of these systems into electronic medical records. 11 Another point of concern in this trial 8 is that almost a quarter of patients discontinued the closed-loop system because of discomfort when wearing the device, indicating that future work should focus on the acceptability of wearing these kinds of multifaceted devices and in motivating patients to do the necessary handling, such as finger-sticking, correctly. The positive feedback of participants at the end of the study indicates that closed-loop systems were received positively by most patients.…”

“…In The Lancet Diabetes & Endocrinology, Charlotte Boughton and colleagues 8 report the results of a randomised controlled trial comparing subcutaneous insulin administration via a fully closed-loop system with conventional subcutaneous insulin therapy in accordance with local clinical practice in two centres (in the UK and Switzerland). They showed that, in patients on enteral or parenteral nutrition (or both), an investigational closed-loop system provides superior glycaemic control to conventional therapy.…”

“…A possible limitation of Boughton and colleagues' analysis 8 is that the closed-loop protocol is detailed, but conventional subcutaneous insulin therapy was pragmatic and done in accordance with local clinical practice. Although absence of a clear protocol for conventional therapy is often the reality due to the variability in patients and circumstances, a standardised protocol with clear glycaemic targets, a minimal number of glucose measurements, and type and timing of insulin adjusted to feeding regimens could have resulted in similar outcomes to those achieved with the closed-loop system.…”