Zone-MPC Automated Insulin Delivery Algorithm Tuned for Pregnancy Complicated by Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) increases the risk for pregnancy complications. Increased time in the pregnancy glucose target range (63-140 mg/dL as suggested by clinical guidelines) is associated with improved pregnancy outcomes that underscores the need for tight glycemic control. While closed-loop control is highly effective in regulating blood glucose levels in individuals with T1D, its use during pregnancy requires adjustments to meet the tight glycemic control and changing insulin requirements with advancing gestation. In this paper, we tailor a zone model predictive controller (zone-MPC), an optimization-based control strategy that uses model predictions, for use during pregnancy and verify its robustness in-silico through a broad range of scenarios. We customize the existing zone-MPC to satisfy pregnancy-specific glucose control objectives by having (i) lower target glycemic zones (i.e., 80-110 mg/dL daytime and 80-100 mg/dL overnight), (ii) more assertive correction bolus for hyperglycemia, and (iii) a control strategy that results in more aggressive postprandial insulin delivery to keep glucose within the target zone. The emphasis is on leveraging the flexible design of zone-MPC to obtain a controller that satisfies glycemic outcomes recommended for pregnancy based on clinical insight. To verify this pregnancy-specific zone-MPC design, we use the UVA/Padova simulator and conduct in-silico experiments on 10 subjects over 13 scenarios ranging from scenarios with ideal metabolic and treatment parameters for pregnancy to extreme scenarios with such parameters that are highly deviant from the ideal. All scenarios had three meals per day and each meal had 40 grams of carbohydrates. Across 13 scenarios, pregnancy-specific zone-MPC led to a 10.3 ± 5.3% increase in the time in pregnancy target range (baseline zone-MPC: 70.6 ± 15.0%, pregnancy-specific zone-MPC: 80.8 ± 11.3%, p < 0.001) and a 10.7 ± 4.8% reduction in the time above the target range (baseline zone-MPC: 29.0 ± 15.4%, pregnancy-specific zone-MPC: 18.3 ± 12.0, p < 0.001). There was no significant difference in the time below range between the controllers (baseline zone-MPC: 0.5 ± 1.2%, pregnancy-specific zone-MPC: 3.5 ± 1.9%, p = 0.1). The extensive simulation results show improved performance in the pregnancy target range with pregnancy-specific zone MPC, suggest robustness of the zone-MPC in tight glucose control scenarios, and emphasize the need for customized glucose control systems for pregnancy.

At-Home Use of a Pregnancy-Specific Zone-MPC Closed-Loop System for Pregnancies Complicated by Type 1 Diabetes: A Single-Arm, Observational Multicenter Study

“…CLC-P was developed for use in pregnancies complicated by type 1 diabetes ( 23 ), and data on supervised use of the current algorithm have been previously reported ( 20 ). Every 5 min, the controller computes an optimal insulin microbolus to keep glucose in a target glucose zone of 80–110 mg/dL (4.4–6.1 mmol/L) during the day and 80–100 mg/dL (4.4–5.6 mmol/L) overnight (12:00 a.m. to 6:00 a.m. ).…”

Developing the UVA/Padova Type 1 Diabetes Simulator: Modeling, Validation, Refinements, and Utility

“…While it is not possible to review all uses of this simulation environment to date, we include a sample to 30 publications spanning 12 years, all of which used the UVA/Padova simulator as a central tool for their developments. 82-111 Overall, a PubMed search (Figure 5) shows that since the introduction of the Minimal Model in 1979, about 555 papers were published on the topics of closed-loop control of diabetes or AID algorithms. Two notable dates mark the beginning of these developments: The 2005 National Institutes of Health (NIH)/Juvenile Diabetes Research Foundation (JDRF)/FDA workshop “Obstacles and Opportunities on the Road to Artificial Pancreas: Closing the Loop” and the 2008 acceptance of the UVA/Padova simulator as a substitute to animal trials for the development of closed-loop algorithms.…”

<strong>At-home use of a pregnancy-specific Zone-MPC closed-loop system for pregnancies complicated by type 1 diabetes: a single arm, observational multicenter study</strong>

“…CLC-P was configured by total daily insulin delivery (manually entered at initiation and then updated if it changed by more than 10%) and physician-prescribed insulin pump treatment parameters (i.e., carbohydrate ratio, insulin sensitivity factor, and basal insulin profile) for personalization of insulin dosing decisions. CLC-P was developed for use in pregnancies complicated by type 1 diabetes (23), and data on supervised use of the current algorithm have been previously reported (20). Every 5 min, the controller computes an optimal insulin microbolus to keep glucose in a target glucose zone of 80-110 mg/dL (4.4-6.1 mmol/L) during the day and 80-100 mg/dL (4.4-5.6 mmol/L) overnight (12:00 A.M. to 6:00 A.M.).…”