Novel Use of Glucagon in a Closed-Loop System for Prevention of Hypoglycemia in Type 1 Diabetes
Open accessAbstract
OBJECTIVE: To minimize hypoglycemia in subjects with type 1 diabetes by automated glucagon delivery in a closed-loop insulin delivery system. RESEARCH DESIGN AND METHODS: Adult subjects with type 1 diabetes underwent one closed-loop study with insulin plus placebo and one study with insulin plus glucagon, given at times of impending hypoglycemia. Seven subjects received glucagon using high-gain parameters, and six subjects received glucagon in a more prolonged manner using low-gain parameters. Blood glucose levels were measured every 10 min and insulin and glucagon infusions were adjusted every 5 min. All subjects received a portion of their usual premeal insulin after meal announcement. RESULTS: Automated glucagon plus insulin delivery, compared with placebo plus insulin, significantly reduced time spent in the hypoglycemic range (15 ± 6 vs. 40 ± 10 min/day, P = 0.04). Compared with placebo, high-gain glucagon delivery reduced the frequency of hypoglycemic events (1.0 ± 0.6 vs. 2.1 ± 0.6 events/day, P = 0.01) and the need for carbohydrate treatment (1.4 ± 0.8 vs. 4.0 ± 1.4 treatments/day, P = 0.01). Glucagon given with low-gain parameters did not significantly reduce hypoglycemic event frequency (P = NS) but did reduce frequency of carbohydrate treatment (P = 0.05). CONCLUSIONS: During closed-loop treatment in subjects with type 1 diabetes, high-gain pulses of glucagon decreased the frequency of hypoglycemia. Larger and longer-term studies will be required to assess the effect of ongoing glucagon treatment on overall glycemic control.
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Castle et al. were the first to demonstrate that glucagon interventions can be successfully added to an artificial pancreas system as protection against hypoglycemia.
“Castle et al.3 were the first to perform such a study and demonstrate that glucagon interventions can be successfully added to an AP system as a protection against hypoglycemia.”
From Pharmacokinetics Modeling of Exogenous Glucagon in Type 1 Diabetes Mellitus Patients (2013) · cites this paper as [3]
The Conclusions report that automated high-gain glucagon delivery reduced hypoglycemic events compared with placebo in adults with type 1 diabetes, supporting its use as protection in the studied system. The paper calls its approach novel, but does not establish that Castle et al. were the first to perform such a study; it also notes earlier animal studies of automated glucagon delivery. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn bihormonal closed-loop glucose control, glucagon has been used subcutaneously along with insulin for protection against hypoglycemia.
“More recently, in a bihormonal closed-loop glucose control, glucagon has been used subcutaneously along with insulin for protection against hypoglycemia.”
From Pharmacokinetics Modeling of Exogenous Glucagon in Type 1 Diabetes Mellitus Patients (2013) · cites this paper as [3]
In bihormonal closed-loop systems, small doses of glucagon are frequently administered.
“In this context, small doses of glucagon are frequently administered.”
From Pharmacokinetics Modeling of Exogenous Glucagon in Type 1 Diabetes Mellitus Patients (2013) · cites this paper as [3]
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- Authors
- Castle, J. R., Engle, J. M., Youssef, J. E., Massoud, R. G., Yuen, K. C. J., Kagan, R., & Ward, W. K.
- Affiliations
- Oregon Health & Science University (US)
- Legacy Health (US)
- Corresponding author
- Castle, Jessica R.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2010-03-23
- Volume
- 33
- Issue
- 6
- Pages
- 1282-1287
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC2875438
- OpenAlex
- W2154010909
- Cited by
- 232
- References
- 20
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 10 · 2020: 9 · 2019: 15 · 2018: 15 · 2017: 14 · 2016: 17 · 2015: 26 · 2014: 29 · 2013: 22 · 2012: 28
- FWCI
- 17.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Good Samaritan Foundation
- National Institutes of Health (RR024140)
- Oregon Clinical and Translational Research Institute (UL1RR024140, RR024140)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007674)
- National Center for Research Resources (UL1RR024140)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- glucagon, type 1 diabetes, hypoglycemia prevention, artificial pancreas, time in hypoglycemia, glycemic control
- MeSH terms
- Adult, Blood Glucose, Diabetes Mellitus, Type 1, Female, Glucagon, Hormones, Humans, Hypoglycemia, Male, Treatment Outcome
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