Page 321 - Glucose Monitoring Devices

328 CHAPTER 16 The dawn of automated insulin delivery

used in the home setting because it required IV blood sampling and IV insulin
delivery. Though, these systems provided proof of the concept that automated insu-
lin delivery was possible. With technological advancements over the past 30 years,
including the development of CSII pumps and subcutaneous CGM, outpatient
studies employing algorithms to automate insulin delivery have flourished, paving
the way for commercial approval of the first hybrid closed-loop system.
Herein, we review the components necessary for closed-loop systems and the
testing of these systems in various environments ranging from strictly controlled
clinical research centers to transitional environments like hotels and camps, and
finally, to the outpatient setting. The discussion culminates with a review of the first
commercially available system, real-world data on its use, and how other systems
are likely to come to market in the near future.

Continuous subcutaneous insulin infusion therapy: the first
building block in developing a closed-loop system
More than 40 years ago, the first reports on portable CSII pumps were published
[7,8]. These initial systems demonstrated the feasibility of using CSII to administer
insulin by deploying a miniature, battery-driven syringe pump that allowed for both
basal insulin delivery and bolus insulin delivery to cover carbohydrate intake [7].
Despite the improvement in glycemic control demonstrated with early pump
therapy studies, the penetration of the device into the clinical care of those with
diabetes lagged. After the DCCT demonstrated the beneficial effect of intensive
insulin therapy and with modernization and refinement of CSII pumps, the use of
this mode of insulin delivery increased around the turn of the century. Recent
registry data demonstrated that individuals with diabetes could achieve more
targeted glycemic control using pump therapy as compared to those on multiple
daily injections [9e11]; yet, data from the type 1 diabetes exchange indicate that
only w60% of registry participants use CSII therapy [12].

Continuous glucose monitors: the second step in the
construction of a closed-loop system
Exploration of technologies that allow for real-time sensor glucose readings through
interstitial fluid measurements began nearly 30 years ago, with the first commer-
cially available sensor being approved in 1999. Yet, in the years following its market
launch, conflicting results from early clinical studies surfaced. Skepticism about the
inaccuracy of the earliest generation sensors led to limited uptake in clinical
practice. In 2008, the landmark Juvenile Diabetes Research Foundation (JDRF)
CGM in the T1D study provided compelling results regarding the potential benefits
that could be achieved with the regular use of sensor technology [13]. Importantly,
while the study was conducted in three cohorts (pediatrics defined as 8e14 years