Application of Zone Model Predictive Control Artificial Pancreas During Extended Use of Infusion Set and Sensor: A Randomized Crossover-Controlled Home-Use Trial

Abstract

OBJECTIVEAs artificial pancreas (AP) becomes standard of care, consideration of extended use of insulin infusion sets (IIS) and continuous glucose monitors (CGMs) becomes vital. We conducted an outpatient randomized crossover study to test the safety and efficacy of a zone model predictive control (zone-MPC)–based AP system versus sensor augmented pump (SAP) therapy in which IIS and CGM failures were provoked via extended wear to 7 and 21 days, respectively.RESEARCH DESIGN AND METHODSA smartphone-based AP system was used by 19 adults (median age 23 years [IQR 10], mean 8.0 ± 1.7% HbA1c) over 2 weeks and compared with SAP therapy for 2 weeks in a crossover, unblinded outpatient study with remote monitoring in both study arms.RESULTSAP improved percent time 70–140 mg/dL (48.1 vs. 39.2%; P = 0.016) and time 70–180 mg/dL (71.6 vs. 65.2%; P = 0.008) and decreased median glucose (141 vs. 153 mg/dL; P = 0.036) and glycemic variability (SD 52 vs. 55 mg/dL; P = 0.044) while decreasing percent time <70 mg/dL (1.3 vs. 2.7%; P = 0.001). AP also improved overnight control, as measured by mean glucose at 0600 h (140 vs. 158 mg/dL; P = 0.02). IIS failures (1.26 ± 1.44 vs. 0.78 ± 0.78 events; P = 0.13) and sensor failures (0.84 ± 0.6 vs. 1.1 ± 0.73 events; P = 0.25) were similar between AP and SAP arms. Higher percent time in closed loop was associated with better glycemic outcomes.CONCLUSIONSZone-MPC significantly and safely improved glycemic control in a home-use environment despite prolonged CGM and IIS wear. This project represents the first home-use AP study attempting to provoke and detect component failure while successfully maintaining safety and effective glucose control.

ISPAD Clinical Practice Consensus Guidelines 2018: Diabetes technologies

“…“Free‐living” outpatient studies, despite heterogeneous design and a range of different automated insulin delivery systems, have invariably demonstrated safety and efficacy. Very young children, adolescents, adolescents with sub‐optimal control, and adults all demonstrated a 10% to 20% improvement in TIR compared to insulin pumps, SAP or SAP + LGS, and less time spent with hypoglycemia. Some studies used automated insulin delivery overnight only, while others applied automated insulin delivery for 24 hours a day .…”

“…Some have explored the use of a small dose of basal insulin, like glargine, to help minimize this complication . Widespread adoption of this has not occurred, and many groups continue to explore how to develop improved infusion sets or fault detection algorithms to advise a user of when insulin delivery may be interrupted …”

“…76 Widespread adoption of this has not occurred, and many groups continue to explore how to develop improved infusion sets 77 or fault detection algorithms to advise a user of when insulin delivery may be interrupted. 78,79 Some studies have documented between a 2-and a 5-fold higher risk of DKA in those on pump therapy. 80,81 Yet, a cornerstone to avoiding such increased rates of DKA is adequate education on the risk of DKA and how to manage persistent hyperglycemia in pumptreated patients.…”

“…All studies consistently showed safety and a 10% to 20% improved time spent in target glucose sensor range of 70 to 180 mg/ dL (3.9-10 mmol/L) with a concomitant reduction in time spent hypoglycemic, in comparison to either conventional insulin pump therapy, or SAP therapy. 79,227,229,235,[237][238][239][240]242,244 In the 24-hour use studies, the improvement in overall time spent in range is mainly due to improved overnight glucose levels. In a meta-analysis that included free living, camp and hotel studies, time in target range of 70 to 180 mg/dL (3.9-10 mmol/L) improved by 12.59% using automated insulin delivery compared to insulin pumps or SAP.…”

Monitoring of Pediatric Type 1 Diabetes

“…Current product labeling prohibits insulin delivery at the CGM sensor site and recent studies have identified insulin preservatives as the major cause of CGM inaccuracy when these devices are in close proximity (112). While understanding current limiting factors paves a path forward for future research and development, there is also a need to prolong insulin infusion site wear time beyond the recommended 2-3 days in order to match CGM sensor wear time (113).…”