Metabolic Effects of Glucagon Stimulations in Type 1 Diabetes and Healthy Controls

Metabolic responses to glucagon beyond the promotion of endogenous glucose production in type 1 diabetes remains poorly explored.

Therefore, we aimed to investigate the metabolic responses to glucagon stimulation in type 1 diabetes and explore whether recent exposure to hypoglycemia would impact glucagon sensitivity.

Twenty-nine participants, 19 with type 1 diabetes and 10 healthy controls, underwent a hyperinsulinemic-euglycemic clamp with 5-stepwise ascending glucagon injections. Metabolic responses were assessed before and during each glucagon injection.

During the glucagon injections, the series of the incremental area under the curve of plasma glucose concentration did not differ between the groups. However, during the first injection of 10 μg of glucagon, participants with type 1 diabetes produced a higher incremental area under the plasma glucose concentration curve than healthy controls. Plasma concentration of nonesterified fatty acids, glycerol, and metabolites from metabolomic analyses did not differ between the groups. In participants with type 1 diabetes, exposure to hypoglycemia did not impact the metabolic responses induced by glucagon.

Generally, metabolic responses to glucagon stimulation in type 1 diabetes are similar to healthy controls. However, elevated glucose production was observed following the lowest glucagon dose in participants with type 1 diabetes compared with healthy controls, indicating enhanced glucagon sensitivity to low-dose glucagon stimulations.