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Man with artificial pancreas device attached to his abdomen.

NIHR Signal ‘Artificial pancreas’ improves glucose control in hospital patients with type 2 diabetes

Published on 13 November 2018

doi: 10.3310/signal-000675

Closed-loop insulin pumps, which continuously monitor blood glucose and administer insulin accordingly, can improve blood glucose control among patients with type 2 diabetes admitted to hospital for non-critical care. Those using the system spent about six hours longer in the target range, and this could hasten their recovery and reduce staff workload.

The number of hospitalised patients with type 2 diabetes is increasing. Glucose control often worsens during illness. Closed-loop pumps have been shown to improve blood glucose control in type 1 diabetes and in critical care settings.

This two-centre study included 136 patients with type 2 diabetes on general hospital wards. Patients using the closed-loop system were in the target blood glucose range 66% of the time compared with 42% for conventional insulin treatment. There was no difference in the risk of low blood glucose.

Use of closed-loop pumps could benefit patients and decrease pressure on hospital staff. However, cost-benefit analysis is needed.

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Why was this study needed?

Approximately 18% of UK hospital beds are occupied by people with diabetes. Both high blood glucose (hyperglycaemia) and low (hypoglycaemia) can delay recovery and increase the risk of complications. However, illness, medication and changes in routine, such as mealtimes, can make it difficult to maintain blood glucose targets.

A Canadian review of 20 studies showed that a newer closed-loop insulin pump, also known as an artificial pancreas, increased the time that patients with type 1 diabetes spent in the target blood glucose range, and decreased the risk of severe hypoglycaemia. This study aimed to see if it could benefit hospitalised patients with type 2 diabetes who need insulin.

What did this study do?

This randomised controlled trial included 136 adults with type 2 diabetes admitted to general wards at two hospitals in the UK and Switzerland with raised blood sugar who needed insulin. Two-thirds of patients were already having insulin as part of their usual treatment.

Patients were assigned to insulin delivery via the closed loop system or to continue their usual insulin and other glucose lowering treatment, adjusted by clinicians according to conventional blood glucose measurements. All patients wore an implanted continuous glucose monitor to record their glucose levels and were followed up to 15 days or until hospital discharge.

Randomisation was balanced according to patient BMI, blood glucose control and prior insulin need. Patients in the closed loop group had slightly more co-existing illnesses, which may account for longer treatment in that group. Patients and assessors were aware of group allocation.

What did it find?

  • Closed-loop insulin delivery increased the percentage of time that blood glucose was in the target range of 100-180 mg per decilitre (5.6 to 10.0 mmol per litre) by about 6 hours per day: 65.8% of the time in range (±16.8%) compared with 41.5% (±16.9%) in the control group (mean difference 24.3%, 95% confidence interval [CI] 18.6 to 30.0).
  • The average blood glucose measurement was lower in the closed-loop group than in the control group (154±29 vs 188±43 mg per decilitre [8.6±1.6 vs 10.5±2.4 mmol per litre]; difference 35 mg per decilitre [2.0 mmol per litre], 95% CI 23 to 47 [1.3 to 2.6 mmol per litre]).
  • Fewer patients using the closed-loop system had any glucose measures exceeding the target range (23.6% vs 49.5%, mean difference 25.9%, 95% CI 19.2 to 32.7), and fewer patients had clinically significant hyperglycaemia (blood glucose exceeding 360 mg per decilitre). However, there was no difference in the proportion of patients below the glucose target and no difference in hypoglycaemia between groups.
  • Despite differences in blood glucose control, there was no difference in the average total daily dose of insulin delivered (44.4 U vs 40.2 U in the control group). 
  • Overall, 54 of 62 patients (87%) using the closed-loop system reported that they were happy with their glucose levels during the trial, and 61 of 62 (98%) said they were happy to have their glucose levels controlled in this way. All said they would recommend the system to a friend or family member during hospitalisation.

What does current guidance say on this issue?

NICE guidelines on the management of diabetes outline patient indications for continuous subcutaneous insulin or insulin pumps, in general.

2016 guidance on the use of the MiniMed Paradigm Veo closed-loop system currently advises this as an option only for people with type 1 diabetes who have disabling hypoglycaemia despite optimal management with a standard pump, and providing that usage data is collected.

 The 2011 Quality Standard for diabetes gives inpatient recommendations, specific to type 1 diabetes. When admitted to hospital it’s advised that patients receive specialist input from a multidisciplinary diabetes team, and are supported in continuing to self-manage and administer their own insulin if appropriate.

What are the implications?

The findings suggest that closed-loop systems could improve glucose control for hospitalised patients with type 2 diabetes. However, there are important practical considerations at this stage. A vast number of patients could potentially be eligible for this treatment. The cost of widespread use would be high, and it’s unclear whether this would translate into reduced hospital stays and reduced complications.

The Canadian review of type 1 diabetes found that while closed-loop systems improved blood glucose control, the high costs were associated with a minimal increase in quality of life. As such it wasn’t clear whether the system would be cost effective.

Citation and Funding

Bally L, Thabit H, Hartnell S et al. Closed-loop insulin delivery for glycemic control in noncritical care. N Engl J Med. 2018;379(6):547-56.

This study was funded by Diabetes UK, the Swiss National Science Foundation, the European Foundation for the Study of Diabetes, the JDRF, the National Institute for Health Research Cambridge Biomedical Research Centre, and a Wellcome Strategic Award.

Abbott Diabetes Care supplied discounted continuous glucose-monitoring devices, sensors, and details regarding communication protocol.

Dr Bally received financial support from University Hospital Bern, University of Bern, and the Swiss Diabetes Foundation.

Bibliography

Diabetes UK. Inpatient care for people with diabetes. London: Diabetes UK; 2017.

Health Quality Ontario Continuous monitoring of glucose for type 1 diabetes: a health technology assessment. Ont Health Technol Assess Ser. 2018;18(2):1–160.

JBDS-IP. Self-management of diabetes in hospital. London: Joint British Diabetes Societies for Inpatient Care Group; 2012.

Kerr M. Inpatient care for people with diabetes: the economic case for change. London: NHS Diabetes; 2011.

NICE. Continuous subcutaneous insulin infusion for the treatment of diabetes mellitus. TA151. London: National Institute for Health and Care Excellence; 2008.

NICE. Integrated sensor-augmented pump therapy systems for managing blood glucose levels in type 1 diabetes (the MiniMed Paradigm Veo system and the Vibe and G4 PLATINUM CGM system). DG21. London: National Institute for Health and Care Excellence; 2016.

NICE. Diabetes in adults. QS6. London: National Institute for Health and Care Excellence; updated 2016.

Why was this study needed?

Approximately 18% of UK hospital beds are occupied by people with diabetes. Both high blood glucose (hyperglycaemia) and low (hypoglycaemia) can delay recovery and increase the risk of complications. However, illness, medication and changes in routine, such as mealtimes, can make it difficult to maintain blood glucose targets.

A Canadian review of 20 studies showed that a newer closed-loop insulin pump, also known as an artificial pancreas, increased the time that patients with type 1 diabetes spent in the target blood glucose range, and decreased the risk of severe hypoglycaemia. This study aimed to see if it could benefit hospitalised patients with type 2 diabetes who need insulin.

What did this study do?

This randomised controlled trial included 136 adults with type 2 diabetes admitted to general wards at two hospitals in the UK and Switzerland with raised blood sugar who needed insulin. Two-thirds of patients were already having insulin as part of their usual treatment.

Patients were assigned to insulin delivery via the closed loop system or to continue their usual insulin and other glucose lowering treatment, adjusted by clinicians according to conventional blood glucose measurements. All patients wore an implanted continuous glucose monitor to record their glucose levels and were followed up to 15 days or until hospital discharge.

Randomisation was balanced according to patient BMI, blood glucose control and prior insulin need. Patients in the closed loop group had slightly more co-existing illnesses, which may account for longer treatment in that group. Patients and assessors were aware of group allocation.

What did it find?

  • Closed-loop insulin delivery increased the percentage of time that blood glucose was in the target range of 100-180 mg per decilitre (5.6 to 10.0 mmol per litre) by about 6 hours per day: 65.8% of the time in range (±16.8%) compared with 41.5% (±16.9%) in the control group (mean difference 24.3%, 95% confidence interval [CI] 18.6 to 30.0).
  • The average blood glucose measurement was lower in the closed-loop group than in the control group (154±29 vs 188±43 mg per decilitre [8.6±1.6 vs 10.5±2.4 mmol per litre]; difference 35 mg per decilitre [2.0 mmol per litre], 95% CI 23 to 47 [1.3 to 2.6 mmol per litre]).
  • Fewer patients using the closed-loop system had any glucose measures exceeding the target range (23.6% vs 49.5%, mean difference 25.9%, 95% CI 19.2 to 32.7), and fewer patients had clinically significant hyperglycaemia (blood glucose exceeding 360 mg per decilitre). However, there was no difference in the proportion of patients below the glucose target and no difference in hypoglycaemia between groups.
  • Despite differences in blood glucose control, there was no difference in the average total daily dose of insulin delivered (44.4 U vs 40.2 U in the control group). 
  • Overall, 54 of 62 patients (87%) using the closed-loop system reported that they were happy with their glucose levels during the trial, and 61 of 62 (98%) said they were happy to have their glucose levels controlled in this way. All said they would recommend the system to a friend or family member during hospitalisation.

What does current guidance say on this issue?

NICE guidelines on the management of diabetes outline patient indications for continuous subcutaneous insulin or insulin pumps, in general.

2016 guidance on the use of the MiniMed Paradigm Veo closed-loop system currently advises this as an option only for people with type 1 diabetes who have disabling hypoglycaemia despite optimal management with a standard pump, and providing that usage data is collected.

 The 2011 Quality Standard for diabetes gives inpatient recommendations, specific to type 1 diabetes. When admitted to hospital it’s advised that patients receive specialist input from a multidisciplinary diabetes team, and are supported in continuing to self-manage and administer their own insulin if appropriate.

What are the implications?

The findings suggest that closed-loop systems could improve glucose control for hospitalised patients with type 2 diabetes. However, there are important practical considerations at this stage. A vast number of patients could potentially be eligible for this treatment. The cost of widespread use would be high, and it’s unclear whether this would translate into reduced hospital stays and reduced complications.

The Canadian review of type 1 diabetes found that while closed-loop systems improved blood glucose control, the high costs were associated with a minimal increase in quality of life. As such it wasn’t clear whether the system would be cost effective.

Citation and Funding

Bally L, Thabit H, Hartnell S et al. Closed-loop insulin delivery for glycemic control in noncritical care. N Engl J Med. 2018;379(6):547-56.

This study was funded by Diabetes UK, the Swiss National Science Foundation, the European Foundation for the Study of Diabetes, the JDRF, the National Institute for Health Research Cambridge Biomedical Research Centre, and a Wellcome Strategic Award.

Abbott Diabetes Care supplied discounted continuous glucose-monitoring devices, sensors, and details regarding communication protocol.

Dr Bally received financial support from University Hospital Bern, University of Bern, and the Swiss Diabetes Foundation.

Bibliography

Diabetes UK. Inpatient care for people with diabetes. London: Diabetes UK; 2017.

Health Quality Ontario Continuous monitoring of glucose for type 1 diabetes: a health technology assessment. Ont Health Technol Assess Ser. 2018;18(2):1–160.

JBDS-IP. Self-management of diabetes in hospital. London: Joint British Diabetes Societies for Inpatient Care Group; 2012.

Kerr M. Inpatient care for people with diabetes: the economic case for change. London: NHS Diabetes; 2011.

NICE. Continuous subcutaneous insulin infusion for the treatment of diabetes mellitus. TA151. London: National Institute for Health and Care Excellence; 2008.

NICE. Integrated sensor-augmented pump therapy systems for managing blood glucose levels in type 1 diabetes (the MiniMed Paradigm Veo system and the Vibe and G4 PLATINUM CGM system). DG21. London: National Institute for Health and Care Excellence; 2016.

NICE. Diabetes in adults. QS6. London: National Institute for Health and Care Excellence; updated 2016.

Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care

Published on 26 June 2018

Bally, L.,Thabit, H.,Hartnell, S.,Andereggen, E.,Ruan, Y.,Wilinska, M. E.,Evans, M. L.,Wertli, M. M.,Coll, A. P.,Stettler, C.,Hovorka, R.

N Engl J Med , 2018

Background In patients with diabetes, hospitalization can complicate the achievement of recommended glycemic targets. There is increasing evidence that a closed-loop delivery system (artificial pancreas) can improve glucose control in patients with type 1 diabetes. We wanted to investigate whether a closed-loop system could also improve glycemic control in patients with type 2 diabetes who were receiving noncritical care. Methods In this randomized, open-label trial conducted on general wards in two tertiary hospitals located in the United Kingdom and Switzerland, we assigned 136 adults with type 2 diabetes who required subcutaneous insulin therapy to receive either closed-loop insulin delivery (70 patients) or conventional subcutaneous insulin therapy, according to local clinical practice (66 patients). The primary end point was the percentage of time that the sensor glucose measurement was within the target range of 100 to 180 mg per deciliter (5.6 to 10.0 mmol per liter) for up to 15 days or until hospital discharge. Results The mean (+/-SD) percentage of time that the sensor glucose measurement was in the target range was 65.8+/-16.8% in the closed-loop group and 41.5+/-16.9% in the control group, a difference of 24.3+/-2.9 percentage points (95% confidence interval [CI], 18.6 to 30.0; P<0.001); values above the target range were found in 23.6+/-16.6% and 49.5+/-22.8% of the patients, respectively, a difference of 25.9+/-3.4 percentage points (95% CI, 19.2 to 32.7; P<0.001). The mean glucose level was 154 mg per deciliter (8.5 mmol per liter) in the closed-loop group and 188 mg per deciliter (10.4 mmol per liter) in the control group (P<0.001). There was no significant between-group difference in the duration of hypoglycemia (as defined by a sensor glucose measurement of <54 mg per deciliter; P=0.80) or in the amount of insulin that was delivered (median dose, 44.4 U and 40.2 U, respectively; P=0.50). No episode of severe hypoglycemia or clinically significant hyperglycemia with ketonemia occurred in either trial group. Conclusions Among inpatients with type 2 diabetes receiving noncritical care, the use of an automated, closed-loop insulin-delivery system resulted in significantly better glycemic control than conventional subcutaneous insulin therapy, without a higher risk of hypoglycemia. (Funded by Diabetes UK and others; ClinicalTrials.gov number, NCT01774565 .).

Expert commentary

Closed loop insulin administration is understood as advantageous in type 1 diabetes and also as life-saving in emergency room settings for both non-diabetic and diabetic patients with threatening glycaemic fluctuations. However, non-specialist management of type 2 diabetes during non-critical, often indirectly-related care has lagged behind with sometimes serious cost.

This paper addresses the latter case for medium term (up to a fortnight) closed loop, subcutaneous insulin administration, comparing it with conventional insulin therapy, all data being captured with masked, subcutaneous glucose-sensors. The results demonstrated much improved control in the closed loop group occurred despite a coincidentally greater underlying burden of concurrent illness and a protocol that excluded specific timing control of meals, long-acting insulin injection or manual prandial boosts.

Closed loop systems require training and care, but optimised systems are now available and could be routine. The health economics and human consequences demand that attention is paid to instigating them as a necessity for type 2 diabetic admissions especially in settings where diabetic care may not be the speciality.

M Joan Taylor, Professor of Pharmaceutics, De Montfort University

Expert commentary

The burden of diabetes is increasing, as is the proportion of hospital in-patients with diabetes. This study evaluates an alternative technology an automated closed-loop (also known as Artificial Pancreas) for improving the glucose control among hospital in-patients with diabetes.

The target glucose range was 5.6 to 10.0 mmol/L, with the standard care patients spending 12 hours/day hyperglycaemic (mean glucose 10.4 mmol/L). The closed-loop group spent about six hours more within range and six hours less with glucose levels 10.0 mmol/L or more.

The study highlights the inadequacy of current in-patient diabetes care and suggests that new technologies may allow for in-patient care that is safer and more effective than current clinical approaches.

Dr HR Murphy, Professor of Medicine (Diabetes and Antenatal Care), Norwich Medical School