Frequent low blood sugar episodes can have negative physiological and emotional consequences in people with type 1 diabetes, and just the fear of hypoglycaemia is the biggest barrier to achieving good glucose control for many.

In our research group, we are therefore working on a detailed characterization of glucagon efficacy as an important part of efforts to develop a glucagon dosing algorithm to provide the best prevention and treatment of low blood sugar. With this experiment, we have demonstrated that it is not the rate of decline, but rather the quantity of insulin, that impacts the effect of glucagon.

Previous trials have shown that the use of both glucagon and insulin in a mechanical artificial pancreas can reduce the incidence of low blood sugar as compared with pumps using insulin alone. Despite this promising development, however, the use of glucagon is not sufficient to prevent or treat hypoglycaemia in all cases.

Our research group has been working for a number of years on characterizing the factors that can influence glucagon efficacy with a view to incorporating those variables into the pump’s dosing algorithm. The aim of this experiment was to identify whether the rate at which blood sugar is falling can affect glucagon’s ability to raise the blood sugar level. The trial included ten insulin pump-treated patients with type 1 diabetes, who attended two experiment days. Using an insulin-glucose clamp technique – a method that can control blood glucose and insulin levels very precisely – participants’ blood sugar was either rapidly or slowly reduced. At the low blood sugar threshold, a low dose of glucagon was injected subcutaneously, and changes in blood sugar were observed in the hours following. 

In line with our expectations, the result of the experiment showed that the rate of decline of blood sugar, taken in isolation, does not influence glucagon efficacy. On the basis of previous clinical data, it has been hypothesized that glucagon was less effective if it followed a rapid fall in blood sugar, but, with our experiment, we have now demonstrated that it is not the rate of decline, but rather the quantity of insulin, that impacts the effect of glucagon.

CONTACT
Christian Laugesen
MD, PhD Fellow
Diabetes Technology Research, Steno Diabetes Center Copenhagen, Gentofte
christian.laugesen@regionh.dk

Ajenthen G. Ranjan
MD, PhD, Postdoc Fellow
Diabetes Technology Research, Steno Diabetes Center Copenhagen, Gentofte
ajenthen.ranjan@regionh.dk

READ THE ARTICLE HERE
Laugesen C, Schmidt S, Holst JJ, Nørgaard K, Ranjan AG. The effect of preceding glucose decline rate on low-dose glucagon efficacy in individuals with type 1 diabetes: A randomized crossover trial. Diabetes Obes Metab. 2021;1–6.
https://doi.org/10.1111/dom.14301
Published: 18 December 2020 – Open Access.