Page 320 - Glucose Monitoring Devices

CHAPTER

The dawn of automated

insulin delivery: from 16

promise to product

1
Laura M. Nally, MD , Jennifer L. Sherr, MD, PhD 2
1 Associate Professor, Pediatric Endocrinology, Yale Children’s Diabetes Program, Yale University
2
School of Medicine, New Haven, CT, United States; Instructor, Pediatric Endocrinology, Yale
Children’s Diabetes Program, Yale University School of Medicine, New Haven, CT, United States

Introduction

Although the discovery of insulin nearly a century ago allowed those diagnosed with
type 1 diabetes (T1D) to live with this chronic medical condition, intensive insulin
therapy proven in the Diabetes Control and Complications Trial (DCCT) and the
follow-up Epidemiology of Diabetes Complications to stave off long-term compli-
cations does not come without a price [1,2]. Meticulous self-care in the form of
frequent glucose monitoring and adjustment of insulin regimen, while accounting
for a multitude of factors, including food, physical activity, stress, and sickness,
can be overwhelming [3,4]. Yet, recent technological advancements in the form of
continuous subcutaneous insulin infusion (CSII) pumps and continuous glucose
monitors (CGM) have made it possible to provide more physiologic insulin delivery.
The ultimate goal is to attain physiologically normal glucose levels, thus preventing
short- and long-term complications. To achieve restoration of normal function, a
combination of therapies will likely be required, composed of both immune modu-
lators as well as b-cell regeneration therapies.
Although cellular therapies are developed, a “mechanical cure” may allow
persons with diabetes to achieve targeted glycemia while minimizing the burden
placed on both themselves and, in many cases, their families. A mechanical cure
would ideally be composed of a fully closed-loop insulin delivery system; however,
given the pharmacokinetic properties of currently available rapid-acting insulin
analogs, to date, the focus has been placed on hybrid closed-loop systems.
The concept of a closed-loop system was first realized by Kadish and colleagues
in 1964. That early system incorporated continuous real-time intravenous glucose
readings to adjust intravenous (IV) infusions of insulin, glucose and/or glucagon
[5]. Yet, the determination for adjustments of these substrates was made by a
clinician monitoring the system constantly, making the practical application of the
system nearly impossible. A decade later, the Biostator was introduced, automating
the process. An algorithm on a microcomputer used real-time whole blood analyses
of glucose levels to automate insulin delivery [6]. However, this system could not be

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