Inpatient trial of an artificial pancreas based on multiple model probabilistic predictive control with repeated large unannounced meals

Abstract

Background: Closed-loop control of blood glucose levels in people with type 1 diabetes offers the potential to reduce the incidence of diabetes complications and reduce the patients' burden, particularly if meals do not need to be announced. We therefore tested a closed-loop algorithm that does not require meal announcement.

Materials and methods: A multiple model probabilistic predictive controller (MMPPC) was assessed on four patients, revised to improve performance, and then assessed on six additional patients. Each inpatient admission lasted for 32 h with five unannounced meals containing approximately 1 g/kg of carbohydrate per admission. The system used an Abbott Diabetes Care (Alameda, CA) Navigator(®) continuous glucose monitor (CGM) and Insulet (Bedford, MA) Omnipod(®) insulin pump, with the MMPPC implemented through the artificial pancreas system platform. The controller was initialized only with the patient's total daily dose and daily basal pattern.

Results: On a 24-h basis, the first cohort had mean reference and CGM readings of 179 and 167 mg/dL, respectively, with 53% and 62%, respectively, of readings between 70 and 180 mg/dL and four treatments for glucose values <70 mg/dL. The second cohort had mean reference and CGM readings of 161 and 142 mg/dL, respectively, with 63% and 78%, respectively, of the time spent euglycemic. There was one controller-induced hypoglycemic episode. For the 30 unannounced meals in the second cohort, the mean reference and CGM premeal, postmeal maximum, and 3-h postmeal values were 139 and 132, 223 and 208, and 168 and 156 mg/dL, respectively.

Conclusions: The MMPPC, tested in-clinic against repeated, large, unannounced meals, maintained reasonable glycemic control with a mean blood glucose level that would equate to a mean glycated hemoglobin value of 7.2%, with only one controller-induced hypoglycemic event occurring in the second cohort.

FIG. 1.

(Left) First cohort and (right) second cohort risk and glucose threshold. Because the nocturnal controller for the second cohort ignores uncertainty, it spreads a given bolus over 75 min. Color images available online at www.liebertonline.com/dia

FIG. 2.

(left) Point and (right) rate Error Grid Analysis (EGA) plots. The values shown are for the last six patients. BG, blood glucose. Color images available online at www.liebertonline.com/dia

FIG. 3.

Summary plots: (top) results for patients 1–4 and (bottom) results for patients 5–10. Data are mean±1 SD values. Color images available online at www.liebertonline.com/dia