In silico evaluation of a Parallel Control-based Coordinated Dual-Hormone Artificial Pancreas with Insulin on Board Limitation

A closed-loop glucose control system with automatic insulin and glucagon delivery (dual-hormone artificial pancreas) has the potential to reduce the self-management and the risk of hypo- and hyperglycemia in type 1 diabetic subjects. A novel dual-hormone closed-loop system based on a parallel control structure with intrinsic coordination among insulin and glucagon delivery is presented here, and the potential benefit of incorporating insulin-on-board limitation in such scheme is analyzed. To this end, the coordinated configuration (CC) has been extended with insulin-on-board (IOB) limitation through Sliding Mode Reference Conditioning (CC-SMRC), previously successfully tested in the context of single-hormone systems. Performance of CC and CC-SMRC has been compared through an in-silico study using the UVA-Padova simulator, extended to include various sources of variability. Three scenarios have been considered, comprising meals, snacks and exercise. The proposed coordinated strategy with the IOB limitation showed slightly lower time in hypoglycemia in meal and meals+snack scenario (0.00% vs 0.14% in meal scenario; 0.01% vs 0.11% in snack scenario), but they were not statistically significant ( p=0.180 and p=0.179, respectively). However, the reduction during exercise scenario was statistically significant (1.45% vs 3.40%, ). Likewise, the time in range was similar in both configurations during meal and meals+snack scenarios (93.80% vs 94.13%, p=0.803, in meal scenario; 93.97% vs 94.32%, p=0.356, in meals+snack; CC-SMRC vs CC), although it was greater in CC-SMRC during exercise scenario (92.98% vs 91.56%, p=0.023; CC-SMRC vs CC). Moreover, insulin delivery was lower in CC-SMRC during the most demanding exercise scenario (45.91 /day vs 46.53U/day, p=0.001) at the expense of higher glucagon delivery to reduce hypoglycemia ( 1.03±0.83mg/day vs 0.96±0.79, p = 0.001). In conclusion, the coordinated configuration with insulin-on-board limitation demonstrated to be able to improve the performance of the coordinated configuration faced with exercise perturbation.