A bio-inspired glucose controller based on pancreatic β-cell physiology

Abstract

Introduction: Control algorithms for closed-loop insulin delivery in type 1 diabetes have been mainly based on control engineering or artificial intelligence techniques. These, however, are not based on the physiology of the pancreas but seek to implement engineering solutions to biology. Developments in mathematical models of the β-cell physiology of the pancreas have described the glucose-induced insulin release from pancreatic β cells at a molecular level. This has facilitated development of a new class of bio-inspired glucose control algorithms that replicate the functionality of the biological pancreas. However, technologies for sensing glucose levels and delivering insulin use the subcutaneous route, which is nonphysiological and introduces some challenges. In this article, a novel glucose controller is presented as part of a bio-inspired artificial pancreas.

Methods: A mathematical model of β-cell physiology was used as the core of the proposed controller. In order to deal with delays and lack of accuracy introduced by the subcutaneous route, insulin feedback and a gain scheduling strategy were employed. A United States Food and Drug Administration-accepted type 1 diabetes mellitus virtual population was used to validate the presented controller.

Results: Premeal and postmeal mean ± standard deviation blood glucose levels for the adult and adolescent populations were well within the target range set for the controller [(70, 180) mg/dl], with a percent time in range of 92.8 ± 7.3% for the adults and 83.5 ± 14% for the adolescents.

Conclusions: This article shows for the first time very good glucose control in a virtual population with type 1 diabetes mellitus using a controller based on a subcellular β-cell model.

© 2012 Diabetes Technology Society.

Figures

Figure 1

Simulated biphasic insulin release in response to a step in glucose levels at t = 5 min from G = 0 mg/dl to 150 mg/dl (red curve), G = 200 mg/dl (blue curve), G = 300 mg/dl (green curve), and G = 400 mg/dl (cyan curve).

Figure 2

Schematic representation of the mechanistic model of insulin secretion from pancreatic β cells. The readily releasable pool (RRP) has been divided into readily releasable granules located in silent cells with no calcium influx, exocytosis, or release (circles) and readily releasable granules located in triggered cells (dots).

Figure 3

Example of IV control corresponding to adult #001. (A)Plasma glucose concentration corresponding to a meal containing 75 g of carbohydrates. Horizontal red line corresponds to the hypoglycemic threshold. (B) Insulin delivery proposed by the controller.

Figure 4

Block diagram of the presented bio-inspired glucose controller.

Figure 5

Example of insulin delivery by the SC bio-inspired glucose controller. (A) Subcutaneous glucose measurements (dashed blue line); hyper- and hypoglycemia thresholds (red horizontal lines) and meal (bars). (B) premeal partial bolus (PB, blue bar); b-cell model insulin secretion (SR, solid green line); basal insulin (SRb, solid cyan line); insulin feedback (Ky*I, crossed red line), and delivered insulin (U, blue dashed line).

Figure 6

CVGA graph for the FDA-accepted adult population.

Figure 7

CVGA graph for the FDA-accepted adolescent population.