Artificial Pancreas: A Review of Fundamentals and Inpatient and Outpatient Studies

Abstract

The artificial pancreas (AP) is a device for automated modulation of insulin infusion that aims to maintain blood glucose in a nearly normal range. The core of the AP is the control algorithm, which is in charge of computing an effective insulin dose on the basis of continuous glucose monitoring readings. In the last 6 years, AP prototypes based on subcutaneous glucose sensing and subcutaneous insulin delivery have been extensively studied in clinical trials first on hospitalized patients and, more recently, in an outpatient setting. In this chapter we review the state of the art of the field, starting with a description of the various AP system components. In particular, we focus on the control techniques employed in the AP and on the principles on which they are based. We then move to AP testing: the preclinical stage (mostly done in silico), the inpatient clinical studies, and finally the outpatient studies. We also discuss the technological requirements for an ambulatory AP. © 2015 S. Karger AG, BaselAlthough type 1 diabetes is associated with increased morbidity and decreased life expectancy, strong evidence indicates that good metabolic control decreases diabetes complications [1-3]. Tight glucose control, however, increases the risk of hypoglycemia. To make diabetes control easier, new insulin analogues have been developed and infusion devices have been improved. Glucose monitoring has improved, too, with the introduction of devices for continuous glucose monitoring (CGM) which detect in real time the rate and direction of glucose changes. More recently, pumps and CGM devices have been connected to form an integrated system, the so-called 'artificial pancreas' (AP), whose scope is to ensure better glycemic control by frequently changing the insulin infusion rate on the basis of past, present, and forecasted glucose readings, as computed by a suitable control algorithm ( fig. 1).The pathway that led to the present models of AP started with the development of the first portable insulin pump by Kadish [4] in 1964. Prototypes of the AP with intra-