Closed-loop glucose regulation in type 1 diabetes
In Canada, over two million Canadians have diabetes and this number is expected to increase. Type 1 diabetes accounts for about 10% of all cases of diabetes. Nocturnal hypoglycemia is a common event in patients with type 1 diabetes. It remains common even if preventive actions have been taken. The Diabetes Control and Complications Trials showed that about 55% (75% in children) of severe hypoglycemia episodes occur during sleep.
Recent developments of continuous glucose sensors and infusion pumps have motivated the research toward closed-loop systems. In a closed-loop system, the pump regulates its infusion rate automatically in response to the readings of glucose sensors. These systems use control algorithms to determine the proper hormone infusion dosage, typically every 5 to 10 minutes, and are referred to as external artificial pancreas.
Research is under steady progress to develop external artificial pancreas systems for type 1 diabetes. In-patient studies over the last 10 years have shown that single-hormone and dual-hormone artificial pancreas systems can improve glucose control compared to conventional pump therapy. More recently, the field has transitioned towards outpatient studies as a step towards the commercialization of a portable artificial pancreas.
In 2013, we published the first comparison between a dual-hormone artificial pancreas and conventional pump therapy in 15 adult patients for 15 hours[1]. The artificial pancreas reduced the time spent in hypoglycemia from 10.2% to 0% and increased the time spent in target range from 57% to 71%. We subsequently conducted a randomized trial in 30 patients that compared a dual-hormone system, a single-hormone system, and pump therapy for 24 hours in an in-patient setting[2]. Both artificial pancreas systems achieved equivalent times in the target range but the dual-hormone system brought additional benefits in hypoglycemia reduction (the time spent in hypoglycemia was 13.3% for conventional therapy, 3.1% for the single-hormone system, and 1.5% for the dual-hormone system). This paper was the first head-to-head-to-head comparison, and is the first step toward determining whether the use of glucagon provides enough added benefit to outweigh the lower cost and lower complexity of a single-hormone system. We have now moved to outpatient studies where more variability and unpredictability are expected.
For meal control, we developed a novel algorithm that alleviates the need of carbohydrate counting, where the patients instead choose if the meal carbohydrate content is “small”, “large”, or “very large”. Tight post-meal control would be achieved by giving a small pre-meal insulin bolus (based on insulin-to-carbohydrate ratio but not the exact carbohydrate content), and then delivering the remaining insulin following sensor readings.
From the engineering point of view, we are collaborating with companies to integrate the components of the dual-hormone artificial pancreas into a small, practical, wearable system for longer outpatient studies and subsequent commercialization.
[1] Haidar, A., et al., Glucose-responsive insulin and glucagon delivery (dual-hormone artificial pancreas) in adults with type 1 diabetes: a randomized crossover controlled trial. CMAJ 2013. 185(4): p. 297-305
[2] Haidar, A., et al., Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: an open-label randomised controlled crossover trial. The lancet. Diabetes & endocrinology, 2014
Recent developments of continuous glucose sensors and infusion pumps have motivated the research toward closed-loop systems. In a closed-loop system, the pump regulates its infusion rate automatically in response to the readings of glucose sensors. These systems use control algorithms to determine the proper hormone infusion dosage, typically every 5 to 10 minutes, and are referred to as external artificial pancreas.
Research is under steady progress to develop external artificial pancreas systems for type 1 diabetes. In-patient studies over the last 10 years have shown that single-hormone and dual-hormone artificial pancreas systems can improve glucose control compared to conventional pump therapy. More recently, the field has transitioned towards outpatient studies as a step towards the commercialization of a portable artificial pancreas.
In 2013, we published the first comparison between a dual-hormone artificial pancreas and conventional pump therapy in 15 adult patients for 15 hours[1]. The artificial pancreas reduced the time spent in hypoglycemia from 10.2% to 0% and increased the time spent in target range from 57% to 71%. We subsequently conducted a randomized trial in 30 patients that compared a dual-hormone system, a single-hormone system, and pump therapy for 24 hours in an in-patient setting[2]. Both artificial pancreas systems achieved equivalent times in the target range but the dual-hormone system brought additional benefits in hypoglycemia reduction (the time spent in hypoglycemia was 13.3% for conventional therapy, 3.1% for the single-hormone system, and 1.5% for the dual-hormone system). This paper was the first head-to-head-to-head comparison, and is the first step toward determining whether the use of glucagon provides enough added benefit to outweigh the lower cost and lower complexity of a single-hormone system. We have now moved to outpatient studies where more variability and unpredictability are expected.
For meal control, we developed a novel algorithm that alleviates the need of carbohydrate counting, where the patients instead choose if the meal carbohydrate content is “small”, “large”, or “very large”. Tight post-meal control would be achieved by giving a small pre-meal insulin bolus (based on insulin-to-carbohydrate ratio but not the exact carbohydrate content), and then delivering the remaining insulin following sensor readings.
From the engineering point of view, we are collaborating with companies to integrate the components of the dual-hormone artificial pancreas into a small, practical, wearable system for longer outpatient studies and subsequent commercialization.
[1] Haidar, A., et al., Glucose-responsive insulin and glucagon delivery (dual-hormone artificial pancreas) in adults with type 1 diabetes: a randomized crossover controlled trial. CMAJ 2013. 185(4): p. 297-305
[2] Haidar, A., et al., Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: an open-label randomised controlled crossover trial. The lancet. Diabetes & endocrinology, 2014