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

Abstract

ObjectiveTo 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.MethodsThis 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).ResultsOverall, 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.ConclusionsDH 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.

Optimizing Glycemic Control in Type 1 Diabetic Patients using a Deep Learning-Based Artificial Pancreas with a Secure Glucagon and Insulin Delivery System

“…Since glucagon and insulin do not have an immediate effect on the body, administering glucagon or insulin improperly during lifestyle events or natural fluctuations can lead to dangerous blood sugar levels (Slattery, D., et al, 2018;Ramnanan, C, J., et al, 2011). Treatment could have coincided with natural fluctuations in prior attempts utilizing glucagon and insulin in an artificial pancreas, resulting in continued cases of hyperglycemia and hypoglycemia (Haidar, A., et al, 2015;Haider, A., 2019;Jessica, R, Castle., et al, 2018;Lindkvist, E. B., et al, 2023). (Xiao, D., et al, 2023).…”

“…Glucagon is FDA-approved for treating hypoglycemia and is a popular choice for medical facilities and patients due to its simplicity and ease of use, being administered subcutaneously or intravenously (Morris, CH., and Baker, J., 2023). Dual hormone pumps, pump systems utilizing two hormones, have been tested and while the addition of hormones such as glucagon has shown promising results, hypoglycemia continues to be present in trial participants possibly due to imprecise treatment timings (Haidar, A., et al, 2015;Haider, A., 2019;Jessica, R, Castle., et al, 2018;Lindkvist, E. B., et al, 2023).…”

“…This is shown in recent novel artificial pancreas trials where despite advancements involving insulin dosage administration, groups of patients continued to experience moderate to severe hypoglycemia in each trial (Bionic Pancreas Research Group, Russell, S. J., 2022; Haidar A., 2019; Wadwa, R. P., et al, 2023). Currently, there are no clinically approved artificial pancreas systems utilizing both insulin and a different hormone or antidiabetic medication to fully address both hyper and hypoglycemia (Lindkvist, E. B., et al, 2023; Infante, M., et al, 2021) however, the hormone Glucagon has been identified as a possible method to address hypoglycemia. Glucagon is a hormone that gets secreted from the pancreatic alpha cells which contrasts with insulin by stimulating glucose production through increasing glucose concentration in the bloodstream, thus raising blood sugar levels.…”

Contributions to glucagon and pramlintide pharmacokinetics and pharmacodynamics modeling for multi-hormone artificial pancreas systems

“…Of note, the only clinical trials directly comparing SHAP to DHAP therapy are: Castle et al (2010b) 7 , Haidar et al (2015bHaidar et al ( ,a, 2016Haidar et al ( , 2017; Taleb et al (2016); Abitbol et al (2018); Castle et al (2018); Wilson et al (2020b); Castellanos et al (2021), andLindkvist et al (2023).…”