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Closing the loop 

Closing the loop
Closing the loop

Roman Hovorka

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date: 18 June 2019

The standard therapy of type 1 diabetes is based on multiple daily injections of short- and long acting-insulin analogues accompanied by blood glucose self-monitoring. However, treatment goals identified by the Diabetes Control and Complications Trial are difficult to achieve due, at least in part, to a high risk of hypoglycaemia associated with many currents forms of intensive insulin therapy.

Recent technological developments in real-time subcutaneous continuous glucose monitoring (CGM), combined with the continuous subcutaneous insulin infusion (CSII), could potentially reduce this risk. Since late 1990s at least five continuous or semicontinuous glucose monitors have received regulatory approval (1). CGM has been shown to improve glycaemic control in adults with type 1 diabetes, although apparent barriers to effectiveness in children and adolescents remain to be identified (see Chapter (2). The availability of commercial CGM devices has reinvigorated research towards closed-loop systems (3-6), in which insulin is delivered according to real-time needs, as opposed to open-loop systems, which lack real-time responsiveness to changing glucose concentrations. Closed-loop insulin delivery, in which the insulin delivery is informed by the measured glucose concentrations has the potential gradually to revolutionize the management of type 1 diabetes by reducing or eliminating the risk of hypoglycaemia while achieving near-normal glucose levels.

A closed-loop system, also called the ‘artificial pancreas’, comprises three components: a CGM device to measure real-time glucose concentration, a titrating algorithm to compute the amount of insulin needed, and an insulin pump delivering a rapid-acting insulin analogue (see Fig. Only a few prototypes have been developed. Progress has been hindered by suboptimal accuracy and reliability of CGM devices, the relatively slow absorption of subcutaneously administered ‘rapid’-acting insulin analogues, and the lack of adequate control algorithms. So far, testing has been confined to the clinical setting. However, a concentrated effort promises an accelerated progress towards home testing of closed-loop systems. The research focus centres on systems utilizing subcutaneous glucose sensing and subcutaneous insulin delivery. This approach has the greatest potential for a near-future commercial exploitation, although other approaches utilizing intraperitoneal or intravenous sensing/delivery are, in principle, also feasible.

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