Article Text
Abstract
Objective Hypoglycemia is a frequent and potentially dangerous event among patients with diabetes mellitus type 1. Subcutaneous glucagon is an emergency treatment to counteract severe hypoglycemia. The effect of intraperitoneal glucagon delivery is sparsely studied. We performed a direct comparison of the blood glucose response following intraperitoneally, subcutaneously and intravenously administered glucagon.
Research design and methods This is a prospective, randomized, controlled, open-label, crossover trial in 20 octreotide-treated rats. Three interventions, 1 week apart, in a randomized order, were done in each rat. All 20 rats were given intraperitoneal and subcutaneous glucagon injections, from which 5 rats were given intravenous glucagon injections and 15 rats received placebo (intraperitoneal isotonic saline) injection. The dose of glucagon was 5 µg/kg body weight for all routes of administration. Blood glucose levels were measured before and until 60 min after the glucagon/placebo injections.
Results Compared with placebo-treated rats, a significant increase in blood glucose was observed 4 min after intraperitoneal glucagon administration (p=0.009), whereas after subcutaneous and intravenous glucagon administration significant increases were seen after 8 min (p=0.002 and p<0.001, respectively). In intraperitoneally treated compared with subcutaneously treated rats, the increase in blood glucose was higher after 4 min (p=0.019) and lower after 40 min (p=0.005) and 50 min (p=0.011). The maximum glucose response occurred earlier after intraperitoneal compared with subcutaneous glucagon injection (25 min vs 35 min; p=0.003).
Conclusions Glucagon administered intraperitoneally gives a faster glucose response compared with subcutaneously administered glucagon in rats. If repeatable in humans, the more rapid glucose response may be of importance in a dual-hormone artificial pancreas using the intraperitoneal route for administration of insulin and glucagon.
- glucagon
- intraperitoneal
- subcutaneous
- blood glucose
- rats
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Footnotes
ID-F and MKÅm are joint first authors.
Presented at Data from this study were presented as an abstract and poster at the 11th International Conference on 'Advanced Technology and Treatment for Diabetes', February 14–17, 2018, Vienna, Austria.
Contributors ID-F and MKÅ completed the trial, collected and analyzed the data, wrote and edited the manuscript, and are the guarantors of the work. ALF, SMC and SCC contributed to the discussion, and reviewed and edited the manuscript. All authors contributed to the development of the protocol.
Funding The Norwegian Research Council (NRC) is funding the Double Intraperitoneal Artificial Pancreas project (project number 248872) as part of the Centre for Digital Life Norway (digitallifenorway.org). The study is also supported by a scholarship from the Central Norway Regional Health Authority (grant nr 2014/23166) and the Norwegian Medical Association Johan Selmer Kvanes Endowment. The funding sources had no role in the collection, analysis or interpretation of the data.
Competing interests None declared.
Patient consent Not required.
Ethics approval The study was approved by the Norwegian Food Safety Authority (FOTS-ID 10922) and was in accordance with 'The Norwegian Regulation on Animal Experimentation' and 'Directive 2010/63/EU on the protection of animals used for scientific purposes'.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Additional online data supplement is available.