TY - JOUR

T1 - The effect of preceding glucose decline rate on low-dose glucagon efficacy in individuals with type 1 diabetes

T2 - A randomized crossover trial

AU - Laugesen, Christian

AU - Schmidt, Signe

AU - Holst, Jens Juul

AU - Nørgaard, Kirsten

AU - Ranjan, Ajenthen G.

PY - 2021

Y1 - 2021

N2 - Identifying determinants of low-dose glucagon efficacy is important to optimise its utilization for prevention and treatment of hypoglycaemia in individuals with type 1 diabetes. The study objective was to investigate whether the preceding glucose decline rate affects glucose response to low-dose glucagon administration. Ten adults with insulin pump-treated type 1 diabetes were included in this randomized, single-blind, two-way crossover study. Using a hyperinsulinaemic clamp technique, plasma glucose levels were reduced with either a rapid or slow decline rate while maintaining fixed insulin levels. When the plasma glucose level reached 3.9 mmoL/L, insulin and glucose infusions were discontinued and 150 mu g subcutaneous glucagon was administered, followed by 120 minutes of plasma glucose monitoring. The positive incremental area under the glucose curve after administration of low-dose glucagon did not differ between the rapid-decline and slow-decline visits (mean +/- SEM: 220 +/- 49 vs. 174 +/- 31 mmoL/L x min; P = 0.21). Similarly, no differences in total area under the glucose curve, peak plasma glucose, incremental peak plasma glucose, time-to-peak plasma glucose or end plasma glucose were observed. Thus, preceding glucose decline rate did not significantly affect the glucose response to low-dose glucagon.

AB - Identifying determinants of low-dose glucagon efficacy is important to optimise its utilization for prevention and treatment of hypoglycaemia in individuals with type 1 diabetes. The study objective was to investigate whether the preceding glucose decline rate affects glucose response to low-dose glucagon administration. Ten adults with insulin pump-treated type 1 diabetes were included in this randomized, single-blind, two-way crossover study. Using a hyperinsulinaemic clamp technique, plasma glucose levels were reduced with either a rapid or slow decline rate while maintaining fixed insulin levels. When the plasma glucose level reached 3.9 mmoL/L, insulin and glucose infusions were discontinued and 150 mu g subcutaneous glucagon was administered, followed by 120 minutes of plasma glucose monitoring. The positive incremental area under the glucose curve after administration of low-dose glucagon did not differ between the rapid-decline and slow-decline visits (mean +/- SEM: 220 +/- 49 vs. 174 +/- 31 mmoL/L x min; P = 0.21). Similarly, no differences in total area under the glucose curve, peak plasma glucose, incremental peak plasma glucose, time-to-peak plasma glucose or end plasma glucose were observed. Thus, preceding glucose decline rate did not significantly affect the glucose response to low-dose glucagon.

KW - glucagon

KW - hypoglycaemia

KW - pharmacodynamics

KW - type 1 diabetes

KW - INDUCED MILD HYPOGLYCEMIA

U2 - 10.1111/dom.14301

DO - 10.1111/dom.14301

M3 - Journal article

C2 - 33336888

VL - 23

SP - 1057

EP - 1062

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 4

ER -