In the unfortunate case of severe hypoglycaemia, glucagon is the first-line treatment because of its potent and rapid action starting as fast as 5 minutes after subcutaneous or intramuscular injection. Large dose of glucagon such as 1 mg subcutaneous is usually associated with undesirable side-effects such as nausea, vomiting, bloating and headache. The overall objective of this research proposal is to assess the efficacy of lower subcutaneous doses of glucagon (0.1 mg or 0.2 mg) to correct hypoglycaemia compared to the standard dose (1.0 mg) in adults with type 1 diabetes mellitus (T1D). It is postulated that much lower dosages of glucagon (0.1 or 0.2 mg) injected subcutaneously will be just as effective as the current recommended dose of 1.0 mg to correct hypoglycaemia without the undesirable gastro-intestinal side effects.
In the unfortunate case of severe hypoglycaemia, glucagon is the first-line treatment because of its potent and rapid action starting as fast as 5 minutes after subcutaneous or intramuscular injection. Current instructions for the treatment of severe hypoglycaemia call for the immediate injection of 1 mg of glucagon subcutaneously or intramuscularly. Large dose of glucagon such as 1 mg subcutaneous is usually associated with undesirable side-effects such as nausea, vomiting, bloating and headache. Moreover, glucagon emergency kits are relatively expensive (around $100 per kit), thus increasing the financial burden of diabetes on patients and the health care system. The primary objective of this research project is to the study the pharmacological effects of different doses of glucagon injected subcutaneously to correct hypoglycaemia during controlled conditions mimicking a hypoglycaemic event in adults with type 1 diabetes. More specifically, we will be looking at the effects of subcutaneous glucagon injected at 0.1 or 0.2 mg and 1.0 mg to normalized plasma glucose during a hypoglycaemic hyperinsulinemic clamp in subjects with type 1 diabetes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
A first catheter will be inserted for infusion of D-\[6,6-2H2\] glucose and insulin. A second catheter will be inserted for infusion of dextrose. Dextrose infusion will be enriched with D-\[6,6-2H2\] glucose. A third catheter will be inserted for sampling. D-\[6,6-2H2\] glucose will be administered as a priming dose followed by a constant infusion throughout the experiment. Insulin will be administered as a primed continuous infusion. The first two hours will serve as an equilibration period for the tracer while glucose infusion will be adjusted to achieve a plasma glucose concentration of 5 mmol/L. The third hour is considered the baseline period. Following this, dextrose infusion rate will be decreased over a period of 1 hour to attain hypoglycaemia with a target blood glucose level at 2.8 mmol/L. At the end of the fourth hour, a subcutaneous glucagon dose will be given and plasma samples will be drawn for the determination of labelled and unlabelled glucose, plasma insulin and glucagon.
Institut de recherches cliniques de Montréal
Montreal, Quebec, Canada
Incremental area under the curve of plasma glucose concentrations
30-min incremental area under the curve of plasma glucose concentrations starting at the time glucagon is injected subcutaneously
Time frame: 30 minutes
Time to reach glucose levels ≥ 4 mmol/L
Time frame: Up to 2.5 hours
Time to reach glucose levels ≥ 5 mmol/L
Time frame: Up to 2.5 hours
Time-to-peak plasma glucagon concentration
Time-to-peak plasma glucagon concentration after glucagon injection
Time frame: Up to 2.5 hours
Time for 25% of glucagon appearance
Time for 25% of glucagon appearance after glucagon injection
Time frame: Up to 2.5 hours
Time for 50% of glucagon appearance
Time for 50% of glucagon appearance after glucagon injection
Time frame: Up to 2.5 hours
Time for 75% of glucagon appearance
Time for 75% of glucagon appearance after glucagon injection
Time frame: Up to 2.5 hours
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