Tags

Type your tag names separated by a space and hit enter

Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial.
Lancet. 2018 10 13; 392(10155):1321-1329.Lct

Abstract

BACKGROUND

The achievement of glycaemic control remains challenging for patients with type 1 diabetes. We assessed the effectiveness of day-and-night hybrid closed-loop insulin delivery compared with sensor-augmented pump therapy in people with suboptimally controlled type 1 diabetes aged 6 years and older.

METHODS

In this open-label, multicentre, multinational, single-period, parallel randomised controlled trial, participants were recruited from diabetes outpatient clinics at four hospitals in the UK and two centres in the USA. We randomly assigned participants with type 1 diabetes aged 6 years and older treated with insulin pump and with suboptimal glycaemic control (glycated haemoglobin [HbA1c] 7·5-10·0%) to receive either hybrid closed-loop therapy or sensor-augmented pump therapy over 12 weeks of free living. Training on study insulin pump and continuous glucose monitoring took place over a 4-week run-in period. Eligible subjects were randomly assigned using central randomisation software. Allocation to the two study groups was unblinded, and randomisation was stratified within centre by low (<8·5%) or high (≥8·5%) HbA1c. The primary endpoint was the proportion of time that glucose concentration was within the target range of 3·9-10·0 mmol/L at 12 weeks post randomisation. Analyses of primary outcome and safety measures were done in all randomised patients. The trial is registered with ClinicalTrials.gov, number NCT02523131, and is closed to accrual.

FINDINGS

From May 12, 2016, to Nov 17, 2017, 114 individuals were screened, and 86 eligible patients were randomly assigned to receive hybrid closed-loop therapy (n=46) or sensor-augmented pump therapy (n=40; control group). The proportion of time that glucose concentration was within the target range was significantly higher in the closed-loop group (65%, SD 8) compared with the control group (54%, SD 9; mean difference in change 10·8 percentage points, 95% CI 8·2 to 13·5; p<0·0001). In the closed-loop group, HbA1c was reduced from a screening value of 8·3% (SD 0·6) to 8·0% (SD 0·6) after the 4-week run-in, and to 7·4% (SD 0·6) after the 12-week intervention period. In the control group, the HbA1c values were 8·2% (SD 0·5) at screening, 7·8% (SD 0·6) after run-in, and 7·7% (SD 0·5) after intervention; reductions in HbA1c percentages were significantly greater in the closed-loop group compared with the control group (mean difference in change 0·36%, 95% CI 0·19 to 0·53; p<0·0001). The time spent with glucose concentrations below 3·9 mmol/L (mean difference in change -0·83 percentage points, -1·40 to -0·16; p=0·0013) and above 10·0 mmol/L (mean difference in change -10·3 percentage points, -13·2 to -7·5; p<0·0001) was shorter in the closed-loop group than the control group. The coefficient of variation of sensor-measured glucose was not different between interventions (mean difference in change -0·4%, 95% CI -1·4% to 0·7%; p=0·50). Similarly, total daily insulin dose was not different (mean difference in change 0·031 U/kg per day, 95% CI -0·005 to 0·067; p=0·09) and bodyweight did not differ (mean difference in change 0·68 kg, 95% CI -0·34 to 1·69; p=0·19). No severe hypoglycaemia occurred. One diabetic ketoacidosis occurred in the closed-loop group due to infusion set failure. Two participants in each study group had significant hyperglycaemia, and there were 13 other adverse events in the closed-loop group and three in the control group.

INTERPRETATION

Hybrid closed-loop insulin delivery improves glucose control while reducing the risk of hypoglycaemia across a wide age range in patients with suboptimally controlled type 1 diabetes.

FUNDING

JDRF, NIHR, and Wellcome Trust.

Authors+Show Affiliations

Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK.Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Diabetes and Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Manchester University NHS Foundation Trust and University of Manchester, Manchester, UK.Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Diabetes and Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK.Department of Diabetes and Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK.Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.Jaeb Center for Health Research, Tampa, FL, USA.Jaeb Center for Health Research, Tampa, FL, USA.Jaeb Center for Health Research, Tampa, FL, USA.Jaeb Center for Health Research, Tampa, FL, USA.Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK.Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Diabetes and Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK.Royal Hospital for Sick Children, Edinburgh, UK.Leeds Children's Hospital, Leeds, UK.International Diabetes Center, Minneapolis, MN, USA.International Diabetes Center, Minneapolis, MN, USA.Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.Manchester University NHS Foundation Trust and University of Manchester, Manchester, UK.Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK. Electronic address: rh347@cam.ac.uk.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30292578

Citation

Tauschmann, Martin, et al. "Closed-loop Insulin Delivery in Suboptimally Controlled Type 1 Diabetes: a Multicentre, 12-week Randomised Trial." Lancet (London, England), vol. 392, no. 10155, 2018, pp. 1321-1329.
Tauschmann M, Thabit H, Bally L, et al. Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial. Lancet. 2018;392(10155):1321-1329.
Tauschmann, M., Thabit, H., Bally, L., Allen, J. M., Hartnell, S., Wilinska, M. E., Ruan, Y., Sibayan, J., Kollman, C., Cheng, P., Beck, R. W., Acerini, C. L., Evans, M. L., Dunger, D. B., Elleri, D., Campbell, F., Bergenstal, R. M., Criego, A., Shah, V. N., ... Hovorka, R. (2018). Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial. Lancet (London, England), 392(10155), 1321-1329. https://doi.org/10.1016/S0140-6736(18)31947-0
Tauschmann M, et al. Closed-loop Insulin Delivery in Suboptimally Controlled Type 1 Diabetes: a Multicentre, 12-week Randomised Trial. Lancet. 2018 10 13;392(10155):1321-1329. PubMed PMID: 30292578.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial. AU - Tauschmann,Martin, AU - Thabit,Hood, AU - Bally,Lia, AU - Allen,Janet M, AU - Hartnell,Sara, AU - Wilinska,Malgorzata E, AU - Ruan,Yue, AU - Sibayan,Judy, AU - Kollman,Craig, AU - Cheng,Peiyao, AU - Beck,Roy W, AU - Acerini,Carlo L, AU - Evans,Mark L, AU - Dunger,David B, AU - Elleri,Daniela, AU - Campbell,Fiona, AU - Bergenstal,Richard M, AU - Criego,Amy, AU - Shah,Viral N, AU - Leelarathna,Lalantha, AU - Hovorka,Roman, AU - ,, Y1 - 2018/10/03/ PY - 2018/07/09/received PY - 2018/07/26/revised PY - 2018/08/15/accepted PY - 2018/10/8/pubmed PY - 2018/11/6/medline PY - 2018/10/8/entrez SP - 1321 EP - 1329 JF - Lancet (London, England) JO - Lancet VL - 392 IS - 10155 N2 - BACKGROUND: The achievement of glycaemic control remains challenging for patients with type 1 diabetes. We assessed the effectiveness of day-and-night hybrid closed-loop insulin delivery compared with sensor-augmented pump therapy in people with suboptimally controlled type 1 diabetes aged 6 years and older. METHODS: In this open-label, multicentre, multinational, single-period, parallel randomised controlled trial, participants were recruited from diabetes outpatient clinics at four hospitals in the UK and two centres in the USA. We randomly assigned participants with type 1 diabetes aged 6 years and older treated with insulin pump and with suboptimal glycaemic control (glycated haemoglobin [HbA1c] 7·5-10·0%) to receive either hybrid closed-loop therapy or sensor-augmented pump therapy over 12 weeks of free living. Training on study insulin pump and continuous glucose monitoring took place over a 4-week run-in period. Eligible subjects were randomly assigned using central randomisation software. Allocation to the two study groups was unblinded, and randomisation was stratified within centre by low (<8·5%) or high (≥8·5%) HbA1c. The primary endpoint was the proportion of time that glucose concentration was within the target range of 3·9-10·0 mmol/L at 12 weeks post randomisation. Analyses of primary outcome and safety measures were done in all randomised patients. The trial is registered with ClinicalTrials.gov, number NCT02523131, and is closed to accrual. FINDINGS: From May 12, 2016, to Nov 17, 2017, 114 individuals were screened, and 86 eligible patients were randomly assigned to receive hybrid closed-loop therapy (n=46) or sensor-augmented pump therapy (n=40; control group). The proportion of time that glucose concentration was within the target range was significantly higher in the closed-loop group (65%, SD 8) compared with the control group (54%, SD 9; mean difference in change 10·8 percentage points, 95% CI 8·2 to 13·5; p<0·0001). In the closed-loop group, HbA1c was reduced from a screening value of 8·3% (SD 0·6) to 8·0% (SD 0·6) after the 4-week run-in, and to 7·4% (SD 0·6) after the 12-week intervention period. In the control group, the HbA1c values were 8·2% (SD 0·5) at screening, 7·8% (SD 0·6) after run-in, and 7·7% (SD 0·5) after intervention; reductions in HbA1c percentages were significantly greater in the closed-loop group compared with the control group (mean difference in change 0·36%, 95% CI 0·19 to 0·53; p<0·0001). The time spent with glucose concentrations below 3·9 mmol/L (mean difference in change -0·83 percentage points, -1·40 to -0·16; p=0·0013) and above 10·0 mmol/L (mean difference in change -10·3 percentage points, -13·2 to -7·5; p<0·0001) was shorter in the closed-loop group than the control group. The coefficient of variation of sensor-measured glucose was not different between interventions (mean difference in change -0·4%, 95% CI -1·4% to 0·7%; p=0·50). Similarly, total daily insulin dose was not different (mean difference in change 0·031 U/kg per day, 95% CI -0·005 to 0·067; p=0·09) and bodyweight did not differ (mean difference in change 0·68 kg, 95% CI -0·34 to 1·69; p=0·19). No severe hypoglycaemia occurred. One diabetic ketoacidosis occurred in the closed-loop group due to infusion set failure. Two participants in each study group had significant hyperglycaemia, and there were 13 other adverse events in the closed-loop group and three in the control group. INTERPRETATION: Hybrid closed-loop insulin delivery improves glucose control while reducing the risk of hypoglycaemia across a wide age range in patients with suboptimally controlled type 1 diabetes. FUNDING: JDRF, NIHR, and Wellcome Trust. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/30292578/Closed_loop_insulin_delivery_in_suboptimally_controlled_type_1_diabetes:_a_multicentre_12_week_randomised_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(18)31947-0 DB - PRIME DP - Unbound Medicine ER -