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Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies

BMJ 2011; 342 doi: (Published 14 April 2011) Cite this as: BMJ 2011;342:d1855
  1. Roman Hovorka, principal research associate12,
  2. Kavita Kumareswaran, clinical research fellow 13,
  3. Julie Harris, research nurse1,
  4. Janet M Allen, research nurse12,
  5. Daniela Elleri, clinical research fellow12,
  6. Dongyuan Xing, biostatistician4,
  7. Craig Kollman, senior biostatistician4,
  8. Marianna Nodale, research assistant1,
  9. Helen R Murphy, senior research associate1,
  10. David B Dunger, professor of paediatrics12,
  11. Stephanie A Amiel, professor of diabetic medicine5,
  12. Simon R Heller, professor of diabetes6,
  13. Malgorzata E Wilinska, research associate12,
  14. Mark L Evans, senior lecturer13
  1. 1Institute of Metabolic Science, University of Cambridge, UK
  2. 2Department of Paediatrics, University of Cambridge, UK
  3. 3Department of Medicine University of Cambridge, UK
  4. 4The Jaeb Center for Health Research, Tampa, FL 33647, USA
  5. 5Diabetes Research, Weston Education Centre, King’s College London, London, UK
  6. 6Diabetes Centre, Clinical Sciences Centre, Northern General Hospital, Sheffield, UK
  1. Correspondence to: R Hovorka, Institute of Metabolic Science, University of Cambridge, Box 289, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK rh347{at}
  • Accepted 4 February 2011


Objective To compare the safety and efficacy of overnight closed loop delivery of insulin (artificial pancreas) with conventional insulin pump therapy in adults with type 1 diabetes.

Design Two sequential, open label, randomised controlled crossover, single centre studies.

Setting Clinical research facility.

Participants 24 adults (10 men, 14 women) with type 1 diabetes, aged 18-65, who had used insulin pump therapy for at least three months: 12 were tested after consuming a medium sized meal and the other 12 after consuming a larger meal accompanied by alcohol.

Intervention During overnight closed loop delivery, sensor measurements of glucose were fed into a computer algorithm, which advised on insulin pump infusion rates at 15 minute intervals. During control nights, conventional insulin pump settings were applied. One study compared closed loop delivery of insulin with conventional pump therapy after a medium sized evening meal (60 g of carbohydrates) at 1900, depicting the scenario of “eating in.” The other study was carried out after a later large evening meal (100 g of carbohydrates) at 2030, accompanied by white wine (0.75 g/kg ethanol) and depicted the scenario of “eating out.”

Main outcome measures The primary outcome was the time plasma glucose levels were in target (3.91-8.0 mmol/L) during closed loop delivery and a comparable control period. Secondary outcomes included pooled data analysis and time plasma glucose levels were below target (≤3.9 mmol/L).

Results For the eating in scenario, overnight closed loop delivery of insulin increased the time plasma glucose levels were in target by a median 15% (interquartile range 3-35%), P=0.002. For the eating out scenario, closed loop delivery increased the time plasma glucose levels were in target by a median 28% (2-39%), P=0.01. Analysis of pooled data showed that the overall time plasma glucose was in target increased by a median 22% (3-37%) with closed loop delivery (P<0.001). Closed loop delivery reduced overnight time spent hypoglycaemic (plasma glucose ≤3.9 mmol/L) by a median 3% (0-20%), P=0.04, and eliminated plasma glucose concentrations below 3.0 mmol/L after midnight.

Conclusion These two small crossover trials suggest that closed loop delivery of insulin may improve overnight control of glucose levels and reduce the risk of nocturnal hypoglycaemia in adults with type 1 diabetes.

Trial registration NCT00910767 and NCT00944619.


  • We thank Josephine Hayes for administrative support, Angie Watts for laboratory support, Joanna Weston for dietary support, and the staff at Addenbrooke’s Wellcome Trust Clinical Research Facility for their help. Steve Luzio and colleagues measured plasma insulin.

  • Contributors: RH coordinated the studies. MLE, RH, KK, SAA, DBD, SRH, HRM, and MEW co-designed the studies. JH and KK were responsible for screening and enrolment of participants. KK and JH requested informed consent from the participants. JH, KK, JMA, and DE provided patient care, collected the clinical and laboratory data, and contributed to biochemical analysis. MEW carried out randomisation. MEW, DX, MN, RH, KK, and CK carried out or supported the data analysis, including the statistical analyses. RH designed and implemented the glucose controller. RH, KK, MLE, SAA, SRH, HRM, DBD, and MEW contributed to the interpretation of the results and the writing and critical review of the report. RH had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: This study was supported by Diabetes UK (BDA07/0003549), Juvenile Diabetes Research Foundation (22-2006-1113, 22-2007-1801, 22-2009-801, and 22-2009-802), Medical Research Council Centre for Obesity and Related metabolic Diseases, and National Institute for Health Research Cambridge Biomedical Research Centre. Smiths Medical supplied the study pumps and Abbott Diabetes Care supplied the Freestyle Navigator devices and sensors for the eating in scenario. Abbott Diabetes Care read the manuscript before submission. No sponsor had any role in the study design, data collection, data analysis, data interpretation, or writing of the report.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: in the previous 3 years RH has received speaker honorariums from Minimed Medtronic, Lifescan, and Novo Nordisk, served on advisory panel for Animas and Minimed Medtronic, received licence fees from BBraun and Beckton Dickinson, and served as a consultant to Beckton Dickinson, BBraun, and Profil; CK has served as a consultant to Medtronic International Trading Sàrl and Diabetes Technology Management; SAA has served on advisory boards for Medtronic and Johnson and Johnson and has received speaker honorariums for Medtronic, Animas, and Roche; SRH has received speaker honorariums from NovoNordisk, Eli Lilly, Sanofi-Aventis, and Lifescan and served on advisory panels for NovoNordisk and Eli Lily; MLE has received speaker honorariums from Eli Lilly and served on advisory panels for Medtronic, Sanofi-Aventis, and Cellnovo; HRM has received speaker honorariums from Minimed Medtronic; MEW has received license fees from Becton Dickinson and has served as a consultant to Beckton Dickinson; KK, JH, JMA, DE, DX, and MN declare no competing financial interests. RH, MEW, and DBD report patent applications in the area of closed loop delivery of insulin.

  • Ethical approval: This study was approved by Cambridge research ethics committee.

  • Data sharing: The supplemental appendix is available from the corresponding author at rh347{at}

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