Closed-loop artificial pancreas systems: physiological input to enhance next-generation devices

Abstract

To provide an understanding of both the preclinical and clinical aspects of closed-loop artificial pancreas systems, we provide a discussion of this topic as part of this two-part Bench to Clinic narrative. Here, the Bench narrative provides an in-depth understanding of insulin-glucose-glucagon physiology in conditions that mimic the free-living situation to the extent possible in type 1 diabetes that will help refine and improve future closed-loop system algorithms. In the Clinic narrative, Doyle and colleagues compare and evaluate technology used in current closed-loop studies to gain further momentum toward outpatient trials and eventual approval for widespread use.

Figure 1

Plasma insulin, glucagon, and glucose concentrations; meal rate of appearance of ingested carbohydrates; and rates of endogenous glucose production in control (blue) and T1D (red) subjects after a mixed-meal containing 50 g of carbohydrates (glucose). Data obtained from refs. 15 and 16 for the breakfast meal. The shaded parts represent differences between control and T1D subjects that could be targeted with informed algorithms.

Figure 2

Anticipated plasma insulin and glucose concentrations and changes in rates of endogenous glucose production during stress in control (blue) and T1D (red) subjects. The shaded parts represent estimated differences between control and T1D subjects that could be targeted with informed algorithms.

Figure 3

Observed plasma insulin, glucagon, and glucose concentrations; rates of glucose disappearance; and endogenous glucose production in control (blue) subjects (data obtained from ref. 38) and estimated changes in these parameters in T1D (red) subjects after a mixed-meal containing 75 g of carbohydrates (glucose) with 50% Vo_2max exercise for 75 min, starting 2 h after the meal. The shaded parts represent anticipated differences between control and T1D subjects that could be targeted with informed algorithms.

Figure 4

Expected plasma insulin and glucose concentrations and rates of endogenous glucose production in control (blue) and T1D (red) subjects after alcohol intake. The shaded parts represent anticipated differences between control and T1D subjects that could be targeted with informed algorithms.