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

Abstract

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 ClinicalTrials.gov NCT00910767 and NCT00944619.

Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (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.

Figures

Fig 1 Design of two studies comparing closed loop delivery of insulin with conventional insulin pump therapy after two meal scenarios: eating in and eating out

Fig 2 Flow of participants through study comparing closed loop delivery of insulin with conventional insulin pump therapy after a medium sized evening meal (eating in scenario), and study comparing closed loop delivery with insulin pump therapy after a large evening meal accompanied by alcohol (eating out scenario)

Fig 3 Profiles (medians and interquartile ranges) of plasma glucose and insulin concentrations and insulin infusion in eating in scenario (12 participants). Outlying squares represent hypoglycaemic events (glucose level <3.0 mmol/L)

Fig 4 Profiles (medians and interquartile ranges) of plasma glucose and insulin concentrations and insulin infusion in the eating out scenario (12 participants). Outlying squares represent hypoglycaemic events (glucose level <3.0 mmol/L)

Fig 5 Distribution of plasma glucose values during closed loop insulin delivery and conventional insulin pump therapy (continuous subcutaneous insulin infusion) combining data collected from midnight until end of the eating in scenario and the eating out scenario. Percentages represent total time plasma glucose level was below, at, and above target from midnight until end of closed loop delivery