Achieving Normal Glucose In Hospital Settings (Angie01)

• Percent of plasma glucose values within target range 3.9-8.0 mmol/l [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  

• Percent of sensor glucose values within target range 3.9-8.0 mmol/l [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• Percent of plasma and sensor glucose values below 3.9 mmol/l [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• Percent of plasma and sensor glucose values above 8.0 mmol/l [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• Mean plasma and sensor glucose [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• Mean plasma insulin concentration [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• Total basal insulin insulin delivery [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• Low blood glucose index (LBGI) score [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• High blood glucose index (HBGI) score [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• Hyperglycaemic index score [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• Percent of plasma and sensor glucose values below 3.0 mmol/l [ Time Frame: 24 hrs ] [ Designated as safety issue: Yes ]
  
• Standard deviation of plasma glucose [ Time Frame: 24 hrs ] [ Designated as safety issue: No ]
  
• Frequency of hypoglycaemia [ Time Frame: 24 hrs ] [ Designated as safety issue: Yes ]
  
• Frequency of hyperglycaemia [ Time Frame: 24 hrs ] [ Designated as safety issue: Yes ]
  

Algorithm driven closed-loop enables automated subcutaneous delivery of insulin in response to real-time continuous glucose sensor readings. Our studies to date have assessed the safety and efficacy of closed-loop insulin delivery in patients with type 1 diabetes in a controlled setting. For patients with type 2 diabetes treated by diet or non-insulin glucose-lowering medications alone, an episode of acute illness may result in elevated glucose levels necessitating initiation of insulin replacement therapy to optimise glycaemic control. Insulin may also be required in patients with no prior history of diabetes, presenting with 'stress hyperglycaemia'. Closed-loop systems may be of benefit in such insulin-naive patients in whom the optimal dosing regimen is difficult to establish, and may provide a safer method of insulin delivery with the added benefit of continuous monitoring of glucose levels on general hospital wards, thus minimising the likelihood of hyper- and hypoglycaemic events and their known associated worse outcomes.

The study has an open-label, randomised, two-period crossover design. Participants will be randomised to undergo two 24-hour studies in a clinical research facility, during which glucose levels will be controlled by either the computer-based closed-loop algorithm (intervention) or by patients' usual non-insulin glucose-lowering diabetes treatment regimen (control). A continuous glucose sensor will be inserted on arrival for each visit. Participants will consume regular meals (matched on both visits) and carry out daily activities mimicking those occurring in an inpatient setting. Stable glucose isotopes will be administered on the two study occasions to collect data for modeling of glucose turnover around meals and during the overnight period.