Feasibility study of a bio-inspired artificial pancreas in adults with type 1 diabetes

Abstract

Background: This study assesses proof of concept and safety of a novel bio-inspired artificial pancreas (BiAP) system in adults with type 1 diabetes during fasting, overnight, and postprandial conditions. In contrast to existing glucose controllers in artificial pancreas systems, the BiAP uses a control algorithm based on a mathematical model of β-cell physiology. The algorithm is implemented on a miniature silicon microchip within a portable hand-held device that interfaces the components of the artificial pancreas.

Materials and methods: In this nonrandomized open-label study each subject attended for a 6-h fasting study followed by a 13-h overnight and post-breakfast study on a separate occasion. During both study sessions the BiAP system was used, and microboluses of insulin were recommended every 5 min by the control algorithm according to subcutaneous sensor glucose levels. The primary outcome was percentage time spent in the glucose target range (3.9-10.0 mmol/L).

Results: Twenty subjects (55% male; mean [SD] age, 44 [10] years; duration of diabetes, 22 [12] years; glycosylated hemoglobin, 7.4% [0.7%] [57 (7) mmol/mol]; body mass index, 25 [4] kg/m(2)) participated in the fasting study, and the median (interquartile range) percentage time in target range was 98.0% (90.8-100.0%). Seventeen of these subjects then participated in the overnight/postprandial study, where 70.7% (63.9-77.4%) of time was spent in the target range and, reassuringly, 0.0% (0.0-2.3%) of time was spent in hypoglycemia (<3.9 mmol/L).

Conclusions: The BiAP achieves safe glycemic control during fasting, overnight, and postprandial conditions.

Trial registration: ClinicalTrials.gov NCT01534013.

FIG. 1.

Block diagram of the bio-inspired controller. CHO, carbohydrate; I:CHO, insulin:carbohydrate ratio; K, tuning gain; L.G.S., low glucose suspend; s.c. sensor, subcutaneous sensor; RRP, readily releasable pool; SR, secretion rate.

FIG. 2.

Median glucose trend and insulin delivered for all 20 subjects during the 6-h fasting closed-loop study. Red dotted line=median blood (YSI) glucose (±interquartile range); red dashed lines=5^th and 95^th percentiles for blood glucose; blue triangle line=median sensor glucose (±interquartile range); orange bars=mean insulin dose delivered; black dashed lines=upper/lower glucose target thresholds.

FIG. 3.

Median glucose trend and insulin delivered for all 17 subjects during the 13-h overnight and postprandial closed-loop study. Red dotted line=median blood (YSI) glucose (±interquartile range); red dashed lines=5^th and 95^th percentiles for blood glucose; blue triangle line=median sensor glucose (±interquartile range); orange bars=mean insulin dose delivered; black dashed lines=upper/lower glucose target thresholds. A standard breakfast meal containing 40 g of carbohydrates was provided at 06:00 h and announced to the algorithm.