Diabetes Management Continuous Glucose Monitoring Progress with Closed-loop Systems in Type 1 Diabetes Lalantha Leelarathna1 and Roman Hovorka2


1. Clinical Research Associate; 2. Principal Research Associate, Institute of Metabolic Science, University of Cambridge


Abstract


Automated insulin delivery by means of a glucose-responsive closed-loop system has often been cited as the ‘holy grail’ of type 1 diabetes management. Reflecting the technological advances in interstitial glucose measurements and wider use of continuous glucose monitoring, recent research in closed-loop glucose control has focused on the subcutaneous route for glucose measurements and insulin delivery. The primary aim of such systems is to keep blood glucose within the target range while minimising the risk of hypoglycaemia with minimal input from the user. This article examines recent developments in the field of interstitial glucose measurement, limitations of the current generation of devices and implications on the performance of closed-loop systems. Clinical results and the advantages and disadvantages of different closed-loop configurations are summarised. Potential future advances in closed-loop systems are highlighted.


Keywords Closed-loop system, artificial pancreas, continuous glucose monitoring, type 1 diabetes, hypoglycaemia


Disclosure: The authors have no conflicts of interest to declare. Acknowledgements: The authors acknowledge support from the Juvenile Diabetes Research Foundation (#22-2006-1113, #22-2007-1801, #22-2009-801), Diabetes UK (BDA07/0003549, BDA07/0003551), EC FP7 (247138), National Institutes for Health (NIH) (DK085621) and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. Received: 2 August 2010 Accepted: 20 September 2010 Citation: European Endocrinology, 2010;6(2):31–5 Correspondence: Roman Hovorka, Institute of Metabolic Science, University of Cambridge, Box 289, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK. E: rh347@cam.ac.uk


Type 1 diabetes is one of the most common endocrine problems in childhood and adolescence and its incidence is increasing.1,2


Of the


estimated 480,000 children with type 1 diabetes worldwide, nearly a quarter come from the European region, with a steeper increase in incidence in some of the Central and Eastern European countries.3 type 1 diabetes only accounts for 5–10%4


While of the 285 million people with


diabetes in 2010, it remains a serious chronic disorder with increased morbidity, mortality and reduced quality of life.5


Nocturnal hypoglycaemia was common (occurring on 8.5% of nights) and often prolonged (duration ≥2 hours on 23% of nights) during the recently concluded Juvenile Diabetes Research Foundation (JDRF) continuous glucose monitoring (CGM) studies.9


Even in patients with good control, as judged by average


HbA1c, significant glucose excursions occur with periods of silent hyper- and hypoglycaemia.10,11


The development of an automated closed-loop system – also referred to as an artificial electromechanical endocrine pancreas – that could


© TOUCH BRIEFINGS 2010


For practical reasons, the subcutaneous approach for continuous glucose sensing and insulin delivery has become the preferred mode of operation. Other modes, such as the intravenous approach for glucose sensing and insulin delivery, may be of use for example in intensive care settings.


31


The risk of long-term complications, both microvascular and cardiovascular could be reduced by improving glycaemic control.6,7 Despite the availability of therapeutic options such as self-monitoring of blood glucose, structured patient education, rapid-acting insulin analogues and insulin pump therapy, glycaemic control in the majority of patients with type 1 diabetes remains suboptimal. The biggest barrier to intensification of control is the increased risk of hypoglycaemia.8


Components of Closed-loop Insulin Delivery Systems


The generic definition of ‘closed-loop’ is that it is an automatic control system in which an operation, process or mechanism is regulated by feedback. In type 1 diabetes, closed-loop systems continually modulate insulin delivery according to prevailing glucose levels. This is in contrast with currently available conventional insulin pump therapy, whereby insulin is delivered at pre-programmed rates and only intermittently adjusted.


Closed-loop systems comprise three main components (see Figure 1):


• a CGM device; • •


a control algorithm that determines the insulin delivery rate; and a portable electromechanical insulin pump.


overcome the limitations of modern diabetes therapy has long been an aspiration of the diabetes community. The objective of this article is to describe the current state-of-the-art, challenges and future directions for closed-loop systems.


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