Efficacy determinants of subcutaneous microdose glucagon during closed-loop control

Area of Science:

• Biomedical Engineering
• Endocrinology
• Artificial Pancreas Technology

Background:

• Glucagon's effectiveness in preventing hypoglycemia with a closed-loop system varied.
• Adjusting insulin pharmacokinetic (PK) parameters improved glucagon's efficacy.
• The study investigated the role of plasma insulin and glucagon in glucagon's effectiveness.

Purpose of the Study:

• To evaluate the effectiveness of microdose glucagon in preventing hypoglycemia.
• To determine the influence of plasma insulin and glucagon levels on glucagon's efficacy.
• To assess the impact of improved insulin PK parameter modeling on closed-loop glycemic control.

Main Methods:

• Analyzed 36 episodes of glucagon administration in a closed-loop system.
• Categorized episodes as successful or unsuccessful in preventing hypoglycemia (BG<70 mg/dl).
• Measured plasma insulin, plasma glucagon, and blood glucose (BG) levels, alongside BG descent rates.

Main Results:

• Glucagon prevented hypoglycemia in 20 of 36 episodes.
• Hypoglycemic episodes were associated with higher plasma insulin levels and greater estimation errors.
• Higher peak and mean plasma glucagon levels and faster BG descent rates were observed during hypoglycemic episodes.

Conclusions:

• Microdose glucagon is less effective when plasma insulin exceeds controller estimates by >60%.
• Optimized insulin PK parameters enhanced glucagon's efficacy in preventing hypoglycemia.
• Improved insulin level estimation accuracy, potentially via faster-acting insulin formulations, could further enhance closed-loop control.