Closed-loop artificial pancreas systems: engineering the algorithms

Abstract

In this two-part Bench to Clinic narrative, recent advances in both the preclinical and clinical aspects of artificial pancreas (AP) development are described. In the preceding Bench narrative, Kudva and colleagues provide an in-depth understanding of the modified glucoregulatory physiology of type 1 diabetes that will help refine future AP algorithms. In the Clinic narrative presented here, we compare and evaluate AP technology to gain further momentum toward outpatient trials and eventual approval for widespread use. We enumerate the design objectives, variables, and challenges involved in AP development, concluding with a discussion of recent clinical advancements. Thanks to the effective integration of engineering and medicine, the dream of automated glucose regulation is nearing reality. Consistent and methodical presentation of results will accelerate this success, allowing head-to-head comparisons that will facilitate adoption of the AP as a standard therapy for type 1 diabetes.

Figure 1

Taxonomy of the AP design. A specific AP configuration is created by selecting options for each of the major elements shown in the figure. Solid lines demonstrate connections that are always present and dashed lines represent connections that may only be present in some configurations. The tuning, model, and desired glucose concentration are all part of the controller, as signified by the black arrows. Green color distinguishes physiological states or properties from measured or digital signals. Black lines are used to indicate predetermined features of a block, and blue lines indicate signals or actions conducted during closed-loop operation.

Figure 2

Summary of the percentage of time in desired range reported by studies published in the years 2010–2013. The results are plotted against the size of the desired range (upper bound − lower bound), with all studies but one using between 63 and 71 mg/dL as the lower bound (59 mg/dL in ref. 22). A circle, triangle, or square indicates that there were no meals, announced meals, or meals with no announcement/prebolus, respectively, during the time period used to calculate the percent time in range. A red shaded icon indicates that the time period used to calculate percent time in range was longer than 12 h. Multiple icons are used for a single study if there were different protocol branches or if results were reported only for discrete segments of the study (e.g., overnight and postprandial results reported separately).