Clinical evaluation of a novel close-loop insulin delivery system in type 1 diabetes

Abstract

Type 1 diabetes (T1DM) is managed by exogenous insulin administration, either by multiple daily injections (MDI) of insulin or via continuous subcutaneous insulin infusion (CSII). Despite intensive insulin therapy and structured education a significant proportion of people with T1DM are unable to achieve optimal glucose control without the risking recurrent hypoglycaemia. Longstanding hyperglycaemia can lead to microvascular and macrovascular complications, whereas hypoglycaemia can lead to seizures, arrhythmias and ‘dead in bed’ syndrome.

A closed-loop insulin delivery system, consisting of a glucose sensor measuring interstitial glucose, a control algorithm and an insulin pump for subcutaneous insulin delivery, has the potential to improve glucose control, reduce hypoglycaemia, reduce long-term diabetes associated complications and improve overall quality of life. A novel closed-loop system has been developed by the Imperial College Diabetes Technology Team. The Bio-inspired Artificial Pancreas (BiAP), uses a control algorithm based on mathematical model of pancreatic beta-cell physiology implemented in a microchip integrated in small low-powered handheld device.

This thesis outlines the ‘first in human’ clinical evaluation of the Bio-inspired Artificial Pancreas in adults with T1DM. The safety and efficacy of the system has been evaluated incrementally, initially fasting over 6 hours, followed by 13-hour overnight and post-meal study and finally in a 24-hour randomised controlled trial which included assessment of the algorithm without meal announcement. The feasibility of the BiAP system with glucagon was evaluated in a 6-hour fasting study. A separate sub-study evaluating whether glycaemic variability impacts quality of life in adults with type 1 diabetes on either MDI or CSII was also conducted.

The results of the studies demonstrated that the Imperial College closed-loop insulin delivery system is safe and achieved a significant reduction in hypoglycaemia when compared to standard therapy (insulin pump), particularly overnight. Glycaemic variability was shown to have no significant impact on overall or subscale quality of life in adults with type 1 diabetes, irrespective of whether they are on MDI or CSII.