Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

Abstract

Hypoglycaemia remains the main limiting factor in type 1 diabetes management. We developed an insulin-dependent glucagon dosing regimen for treatment of mild hypoglycaemia based on simulations. A validated glucose-insulin-glucagon model was used to describe seven virtual patients with insulin pump-treated type 1 diabetes. In each simulation, one of ten different and individualized subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba-insulin), insulin on board (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD). Insulin bolus sizes were chosen to provide pre-defined insulin levels when PG reached 3.9 mmol/l, where one of 17 subcutaneous glucagon boluses was administered. Optimum glucagon bolus to treat mild hypoglycaemia at varying insulin levels was the lowest dose that in most patients caused PG peak between 5.0 and 10.0 mmol/l and sustained PG ≥ 3.9 mmol/l for 2 hr after the bolus. PG response to glucagon declined with increasing insulin levels. The glucagon dose to optimally treat mild hypoglycaemia depended exponentially on insulin levels, regardless of how insulin was estimated. A 125-μg glucagon dose was needed to optimally treat mild hypoglycaemia when insulin levels were equal to baseline levels. In contrast, glucagon doses >500 μg were needed when se/ba-insulin >2.5, IOB >2.0 U or IOB/TDD >6%. Although the proposed model-based glucagon regimen needs confirmation in clinical trials, this is the first attempt to develop an insulin-dependent glucagon dosing regimen for treatment of insulin-induced mild hypoglycaemia in patients with type 1 diabetes.

A Update on Early Detection and Management of Diabetes: Comparison of Fasting Serum Glucagon among Diabetics and Non-Diabetics

“…These results are in accordance with Ranjan et al that worldwide presence of hypertension and diabetes mellitus exist in all age groups but it is more likely to occur in individuals with higher BMI [15]. Previously, increased BMI increases the risk of developing diabetes type 2.…”

Preference for Subcutaneously Administered Low-Dose Glucagon Versus Orally Administered Glucose for Treatment of Mild Hypoglycemia: A Prospective Survey Study

“…However, several conditions may impair glucagon’s efficacy, i.e., low carbohydrate diets [16], exercise [17], ethanol intake [18], and hyperinsulinemia [19]. Therefore, if low-dose glucagon should be used in everyday treatment of mild hypoglycemia, a variable dosing regimen depending on these factors may be preferable as shown in a simulation study proposing an insulin-dependent glucagon dosing regimen for treatment of mild hypoglycemia [20].…”

Glucagon for hypoglycaemia treatment in type 1 diabetes

“…Haymond et al also demonstrated that the glucose response to Xeris glucagon was blunted immediately after an insulin bolus compared with after an overnight fast 41 . In dual‐hormone closed‐loop studies, high ambient insulin concentrations were correlated with failure of glucagon to prevent and treat hypoglycaemia, 74,78,79 also shown in simulation studies 80 …”