Manual Closed-Loop Insulin Delivery Using a Saddle Point Model Predictive Control Algorithm: Results of a Crossover Randomized Overnight Study

Abstract

Background: The purpose was to assess the efficacy of a new closed-loop algorithm (Saddle Point Model Predictive Control, SP-MPC) in achieving nocturnal normoglycemia while reducing the risk of hypoglycemia in patients with type 1 diabetes.

Method: In this randomized crossover study, 10 adult patients (mean hemoglobin A1c 7.35 ± 1.04%) were assigned to be treated overnight by open loop using sensor-augmented pump therapy (open-loop SAP) or manual closed-loop delivery. During closed loop, insulin doses were calculated using the SP-MPC algorithm and administered as manual boluses every 15 minutes from 9:00 pm to 8:00 am. Patients consumed a self-selected meal (65-125 g of carbohydrates) at 7:00 pm accompanied by their usual prandial bolus. Blood glucose was measured every 30 minutes. The primary endpoints were the time spent in target (70-145 mg/dl) and time spent below 70 mg/dl from 11:00 pm to 8:00 am.

Results: Time spent in target did not differ between closed-loop and open-loop SAP. The number of hypoglycemic events (<70 mg/dl) was reduced 2.8-fold in closed loop (n = 5, median = 0/patient/hour; interquartile range: 0-0.11) as compared to open-loop SAP (n = 14, median = 0.22/patient/hour, 0.02-0.22) ( P = .02). The area under the curve for sensor glucose values >145 mg/dl was significantly lower during closed-loop than during open-loop SAP ( P = .03) as well as HBGI ( P = .02).

Conclusions: This pilot study suggests that the use of the SP-MPC algorithm may improve mean overnight glucose control and reduce the number of hypoglycemic events as compared to SAP therapy.

Keywords: artificial pancreas; closed loop; model predictive control; sensor-augmented pump therapy; type 1 diabetes.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.

Median (curves) and 25th-75th percentiles (shaded areas) of plasma glucose during closed-loop and open-loop SAP nights. The straight dotted lines show the target zone 70-145 mg/dl.