Factors affecting the success of glucagon delivered during an automated closed-loop system in type 1 diabetes

P. A. Bakhtiani, Joseph El Youssef, A. K. Duell, D. L. Branigan, Peter Jacobs, M. R. Lasarev, Jessica Castle, W. K. Ward

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background In bi-hormonal closed-loop systems for treatment of diabetes, glucagon sometimes fails to prevent hypoglycemia. We evaluated glucagon responses during several closed-loop studies to determine factors, such as gain factors, responsible for glucagon success and failure.

Methods We extracted data from four closed-loop studies, examining blood glucose excursions over the 50 min after each glucagon dose and defining hypoglycemic failure as glucose values <60 mg/dl. Secondly, we evaluated hyperglycemic excursions within the same period, where glucose was > 180 mg/dl. We evaluated several factors for association with rates of hypoglycemic failure or hyperglycemic excursion. These factors included age, weight, HbA1c, duration of diabetes, gender, automation of glucagon delivery, glucagon dose, proportional and derivative errors (PE and DE), insulin on board (IOB), night vs. day delivery, and point sensor accuracy.

Results We analyzed a total of 251 glucagon deliveries during 59 closed-loop experiments performed on 48 subjects. Glucagon successfully maintained glucose within target (60-180 mg/dl) in 195 (78%) of instances with 40 (16%) hypoglycemic failures and 16 (6%) hyperglycemic excursions. A multivariate logistic regression model identified PE (p <0.001), DE (p <0.001), and IOB (p <0.001) as significant determinants of success in terms of avoiding hypoglycemia. Using a model of glucagon absorption and action, simulations suggested that the success rate for glucagon would be improved by giving an additional 0.8 μg/kg.

Conclusion We conclude that glucagon fails to prevent hypoglycemia when it is given at a low glucose threshold and when glucose is falling steeply. We also confirm that high IOB significantly increases the risk for glucagon failures. Tuning of glucagon subsystem parameters may help reduce this risk.

Original languageEnglish (US)
Pages (from-to)93-98
Number of pages6
JournalJournal of Diabetes and its Complications
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Glucagon
Type 1 Diabetes Mellitus
Hypoglycemia
Hypoglycemic Agents
Glucose
Insulin
Logistic Models
Age Factors
Automation
Blood Glucose

Keywords

  • Artificial pancreas
  • Closed-Loop
  • Glucagon
  • Hypoglycemia
  • Type 1 diabetes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Factors affecting the success of glucagon delivered during an automated closed-loop system in type 1 diabetes. / Bakhtiani, P. A.; El Youssef, Joseph; Duell, A. K.; Branigan, D. L.; Jacobs, Peter; Lasarev, M. R.; Castle, Jessica; Ward, W. K.

In: Journal of Diabetes and its Complications, Vol. 29, No. 1, 01.01.2015, p. 93-98.

Research output: Contribution to journalArticle

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abstract = "Background In bi-hormonal closed-loop systems for treatment of diabetes, glucagon sometimes fails to prevent hypoglycemia. We evaluated glucagon responses during several closed-loop studies to determine factors, such as gain factors, responsible for glucagon success and failure.Methods We extracted data from four closed-loop studies, examining blood glucose excursions over the 50 min after each glucagon dose and defining hypoglycemic failure as glucose values <60 mg/dl. Secondly, we evaluated hyperglycemic excursions within the same period, where glucose was > 180 mg/dl. We evaluated several factors for association with rates of hypoglycemic failure or hyperglycemic excursion. These factors included age, weight, HbA1c, duration of diabetes, gender, automation of glucagon delivery, glucagon dose, proportional and derivative errors (PE and DE), insulin on board (IOB), night vs. day delivery, and point sensor accuracy.Results We analyzed a total of 251 glucagon deliveries during 59 closed-loop experiments performed on 48 subjects. Glucagon successfully maintained glucose within target (60-180 mg/dl) in 195 (78{\%}) of instances with 40 (16{\%}) hypoglycemic failures and 16 (6{\%}) hyperglycemic excursions. A multivariate logistic regression model identified PE (p <0.001), DE (p <0.001), and IOB (p <0.001) as significant determinants of success in terms of avoiding hypoglycemia. Using a model of glucagon absorption and action, simulations suggested that the success rate for glucagon would be improved by giving an additional 0.8 μg/kg.Conclusion We conclude that glucagon fails to prevent hypoglycemia when it is given at a low glucose threshold and when glucose is falling steeply. We also confirm that high IOB significantly increases the risk for glucagon failures. Tuning of glucagon subsystem parameters may help reduce this risk.",
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