Modeling the effect of glucagon on endogenous glucose production in type 1 diabetes: On the role of glucagon receptor dynamics.

This paper validates a glucoregulatory model including glucagon receptors dynamics in the description of endogenous glucose production (EGP). A set of models from literature are selected for a head-to-head comparison in order to evaluate the role of glucagon receptors. Each EGP model is incorporated into an existing glucoregulatory model and validated using a set of clinical data, where both insulin and glucagon are administered. The parameters of each EGP model are identified in the same optimization problem, minimizing the root mean square error (RMSE) between the simulation and the clinical data. The results show that the RMSE for the proposed receptors-based EGP model was lower when compared to each of the considered models (Receptors approach: 7.13±1.71 mg/dl vs. 7.76±1.45 mg/dl (p=0.066), 8.45±1.38 mg/dl (p=0.011) and 8.99±1.62 mg/dl (p=0.007)). This raises the possibility of considering glucagon receptors dynamics in type 1 diabetes simulators.

Performance of a dual-hormone closed-loop system versus insulin-only closed-loop system in adolescents with type 1 diabetes. A single-blind, randomized, controlled, crossover trial.

Objective: To assess the efficacy and safety of a dual-hormone (DH [insulin and glucagon]) closed-loop system compared to a single-hormone (SH [insulin only]) closed-loop system in adolescents with type 1 diabetes. Methods: This was a 26-hour, two-period, randomized, crossover, inpatient study involving 11 adolescents with type 1 diabetes (nine males [82%], mean ± SD age 14.8 ± 1.4 years, diabetes duration 5.7 ± 2.3 years). Except for the treatment configuration of the DiaCon Artificial Pancreas: DH or SH, experimental visits were identical consisting of: an overnight stay (10:00 pm until 7:30 am), several meals/snacks, and a 45-minute bout of moderate intensity continuous exercise. The primary endpoint was percentage of time spent with sensor glucose values below range (TBR [<3.9 mmol/L]) during closed-loop control over the 26-h period (5:00 pm, day 1 to 7:00 pm, day 2). Results: Overall, there were no differences between DH and SH for the following glycemic outcomes (median [IQR]): TBR 1.6 [0.0, 2.4] vs. 1.28 [0.16, 3.19]%, p=1.00; time in range (TIR [3.9-10.0 mmol/L]) 68.4 [48.7, 76.8] vs. 75.7 [69.8, 87.1]%, p=0.08; and time above range (TAR [>10.0 mmol/L]) 28.1 [18.1, 49.8] vs. 23.3 [12.3, 27.2]%, p=0.10. Mean ( ± SD) glucose was higher during DH than SH (8.7 ( ± 3.2) vs. 8.1 ( ± 3.0) mmol/L, p<0.001) but coefficient of variation was similar (34.8 ( ± 6.8) vs. 37.3 ( ± 8.6)%, p=0.20). The average amount of rescue carbohydrates was similar between DH and SH (6.8 ( ± 12.3) vs. 9.5 ( ± 15.4) grams/participant/visit, p=0.78). Overnight, TIR was higher, TAR was lower during the SH visit compared to DH. During and after exercise (4:30 pm until 7 pm) the SH configuration produced higher TIR, but similar TAR and TBR compared to the DH configuration. Conclusions: DH and SH performed similarly in adolescents with type 1 diabetes during a 26-hour inpatient monitoring period involving several metabolic challenges including feeding and exercise. However, during the night and around exercise, the SH configuration outperformed DH.