Adjustment of Open-Loop Settings to Improve Closed-Loop Results in Type 1 Diabetes: A Multicenter Randomized Trial

Abstract

Context: Closed-loop control (CLC) relies on an individual's open-loop insulin pump settings to initialize the system. Optimizing open-loop settings before using CLC usually requires significant time and effort.

Objective: The objective was to investigate the effects of a one-time algorithmic adjustment of basal rate and insulin to carbohydrate ratio open-loop settings on the performance of CLC.

Design: This study reports a multicenter, outpatient, randomized, crossover clinical trial.

Patients: Thirty-seven adults with type 1 diabetes were enrolled at three clinical sites.

Interventions: Each subject's insulin pump settings were subject to a one-time algorithmic adjustment based on 1 week of open-loop (i.e., home care) data collection. Subjects then underwent two 27-hour periods of CLC in random order with either unchanged (control) or algorithmic adjusted basal rate and carbohydrate ratio settings (adjusted) used to initialize the zone-model predictive control artificial pancreas controller. Subject's followed their usual meal-plan and had an unannounced exercise session.

Main outcomes and measures: Time in the glucose range was 80-140 mg/dL, compared between both arms.

Results: Thirty-two subjects completed the protocol. Median time in CLC was 25.3 hours. The median time in the 80-140 mg/dl range was similar in both groups (39.7% control, 44.2% adjusted). Subjects in both arms of CLC showed minimal time spent less than 70 mg/dl (median 1.34% and 1.37%, respectively). There were no significant differences more than 140 mg/dL.

Conclusions: A one-time algorithmic adjustment of open-loop settings did not alter glucose control in a relatively short duration outpatient closed-loop study. The CLC system proved very robust and adaptable, with minimal (<2%) time spent in the hypoglycemic range in either arm.

Trial registration: ClinicalTrials.gov NCT01929798.

Figures

Figure 1.

Box and whisker plot representation of blood glucose control performance characterized by percent time in clinical range of 32 adult subjects with control or adjusted clinical parameters for (A) the entire trial period, (B) overnight, 5-hour postprandial periods for (C) dinner, (D) breakfast, (E) lunch, and duration of (F) exercise. The dark bars inside each box represent the median value, with the bounds of the box representing the 25%–75% interquartile range. The thin lines represent the minimum and maximum values.

Figure 2.

Blood glucose control performance characterized by median and interquartile range glucose and insulin traces of % time in clinical range of 32 adult subjects with control or adjusted clinical parameters. The solid line represents subjects with control parameters; the dashed line represents subjects with adjusted parameters.

Figure 3.

Blood glucose control performance characterized by median and interquartile range of cumulative time in blood glucose of 32 adult subjects with control or adjusted clinical parameters. The solid line represents subjects with control parameters; the dashed line represents subjects with adjusted parameters.