Clinical evaluation of a personalized artificial pancreas

Abstract

Objective: An artificial pancreas (AP) that automatically regulates blood glucose would greatly improve the lives of individuals with diabetes. Such a device would prevent hypo- and hyperglycemia along with associated long- and short-term complications as well as ease some of the day-to-day burden of frequent blood glucose measurements and insulin administration.

Research design and methods: We conducted a pilot clinical trial evaluating an individualized, fully automated AP using commercial devices. Two trials (n = 22, n(subjects) = 17) were conducted using a multiparametric formulation of model predictive control and an insulin-on-board algorithm such that the control algorithm, or "brain," can be embedded on a chip as part of a future mobile device. The protocol evaluated the control algorithm for three main challenges: 1) normalizing glycemia from various initial glucose levels, 2) maintaining euglycemia, and 3) overcoming an unannounced meal of 30 ± 5 g carbohydrates.

Results: Initial glucose values ranged from 84-251 mg/dL. Blood glucose was kept in the near-normal range (80-180 mg/dL) for an average of 70% of the trial time. The low and high blood glucose indices were 0.34 and 5.1, respectively.

Conclusions: These encouraging short-term results reveal the ability of a control algorithm tailored to an individual's glucose characteristics to successfully regulate glycemia, even when faced with unannounced meals or initial hyperglycemia. To our knowledge, this represents the first truly fully automated multiparametric model predictive control algorithm with insulin-on-board that does not rely on user intervention to regulate blood glucose in individuals with type 1 diabetes.

Figure 1

Clinical results output from two closed-loop trials (study numbers 15 [A] and 10 [B]) demonstrating the ability of the design to effectively and safely overcome daily challenges of individuals with type 1 diabetes, such as hyperglycemia, unannounced meals, and avoiding postprandial hypoglycemia. For both cases, excellent automated glucose control was observed with 54.5 and 64.3% of the time in tight control (80–140 mg/dL). BG, blood glucose.

Figure 2

Percent time in different glycemic ranges for all subjects for outpatient collected data versus study day data as measured by CGM (A and B) and over the study day for all subjects as measured by CGM and YSI (C and D). No subjects experienced hypoglycemia, and they were in the safe range (80–180 mg/dL) for an average of 70% of the time, with a fraction of time in the mild hyperglycemia range and negligible time in the hyperglycemia range, as measured by YSI. *Statistically significant at P < 0.05.

Figure 3

CVGA before and after the study for CGM (A) and YSI (B).⬜, prestudy values; ●, study values. The prestudy values for the YSI CVGA were finger-stick values. The nine categories within the CVGA grid represent different levels of control as follows: accurate control (A-zone), benign deviation into hypoglycemia (lower B-zone), benign deviation into the hyperglycemia range (upper B-zone), benign control (B-zone), overcorrection of hyperglycemia (lower C-zone), overcorrection of hypoglycemia (upper C-zone), failure to manage hypoglycemia (lower D-zone), failure to manage hyperglycemia (upper D-zone), and erroneous control (E-zone).