Fully Closed-Loop Multiple Model Probabilistic Predictive Controller Artificial Pancreas Performance in Adolescents and Adults in a Supervised Hotel Setting

Abstract

Background: Initial Food and Drug Administration-approved artificial pancreas (AP) systems will be hybrid closed-loop systems that require prandial meal announcements and will not eliminate the burden of premeal insulin dosing. Multiple model probabilistic predictive control (MMPPC) is a fully closed-loop system that uses probabilistic estimation of meals to allow for automated meal detection. In this study, we describe the safety and performance of the MMPPC system with announced and unannounced meals in a supervised hotel setting.

Research design and methods: The Android phone-based AP system with remote monitoring was tested for 72 h in six adults and four adolescents across three clinical sites with daily exercise and meal challenges involving both three announced (manual bolus by patient) and six unannounced (no bolus by patient) meals. Safety criteria were predefined. Controller aggressiveness was adapted daily based on prior hypoglycemic events.

Results: Mean 24-h continuous glucose monitor (CGM) was 157.4 ± 14.4 mg/dL, with 63.6 ± 9.2% of readings between 70 and 180 mg/dL, 2.9 ± 2.3% of readings <70 mg/dL, and 9.0 ± 3.9% of readings >250 mg/dL. Moderate hyperglycemia was relatively common with 24.6 ± 6.2% of readings between 180 and 250 mg/dL, primarily within 3 h after a meal. Overnight mean CGM was 139.6 ± 27.6 mg/dL, with 77.9 ± 16.4% between 70 and 180 mg/dL, 3.0 ± 4.5% <70 mg/dL, 17.1 ± 14.9% between 180 and 250 mg/dL, and 2.0 ± 4.5%> 250 mg/dL. Postprandial hyperglycemia was more common for unannounced meals compared with announced meals (4-h postmeal CGM 197.8 ± 44.1 vs. 140.6 ± 35.0 mg/dL; P < 0.001). No participants met safety stopping criteria.

Conclusions: MMPPC was safe in a supervised setting despite meal and exercise challenges. Further studies are needed in a less supervised environment.

Keywords: Artificial pancreas; Clinical trial; Fully closed-loop; Type 1 diabetes.

FIG. 1.

Overview of the study protocol with overlaid carbohydrate treatments ( × s represent SMBG values), system activation and deactivation times (+ signs on days 1 and 4), and meals (triangles at times of CHO ingestion). Note that 3 of 10 patients account for 40 of 56 CHO treatments and that some small-dose triangles represent snacks unrelated to risk of hypoglycemia. CHO, carbohydrate; CL, closed loop; SMBG, self-monitoring of blood glucose.

FIG. 2.

Postdinner and overnight glycemic control. Solid center line represents the average, and dotted lines represent the 25th and 75th percentiles. CGM, continuous glucose monitor; IQR, interquartile range.

FIG. 3.

Comparison of postprandial CGM response for 30 announced and 60 unannounced meals. Unannounced meals <35 g CHO were omitted from this analysis. Dark gray represents announced meals, and light gray represents unannounced meals. Solid line is median, and dashed lines are the 25th and 75th percentiles. Triangles represent hypoglycemia treatments, with the dark fill color occurring with announced meals and the light gray fill color corresponding to unannounced meals.