Effects of subcutaneous, low-dose glucagon on insulin-induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes

TY - JOUR

T1 - Effects of subcutaneous, low-dose glucagon on insulin-induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes

AU - Ranjan, Ajenthen

AU - Schmidt, S

AU - Madsbad, Sten

AU - Holst, Jens Juul

AU - Nørgaard, K

N1 - This article is protected by copyright. All rights reserved.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Aim: To investigate the dose-response relationship of subcutaneous (s.c.) glucagon administration on plasma glucose and on counter-regulatory hormone responses during s.c. insulin-induced mild hypoglycaemia in patients with type 1 diabetes treated with insulin pumps. Methods: Eight insulin pump-treated patients completed a blinded, randomized, placebo-controlled study. Hypoglycaemia was induced in the fasting state by an s.c. insulin bolus and, when plasma glucose reached 3.4 mmol/l [95% confidence interval (CI) 3.2-3.5], an s.c. bolus of either 100, 200, 300 μg glucagon or saline was administered. Plasma glucose, counter-regulatory hormones, haemodynamic variables and side effects were measured throughout each study day. Peak plasma glucose level was the primary endpoint. Results: Plasma glucose level increased significantly by a mean (95% CI) of 2.3 (1.7-3.0), 4.2 (3.5-4.8) and 5.0 (4.3-5.6) mmol/l to 6.1 (4.9-7.4), 7.9 (6.4-9.3) and 8.7 (7.8-9.5) vs 3.6 (3.4-3.9) mmol/l (p < 0.001) after the three different glucagon doses as compared with saline, and the increase was neither correlated with weight nor insulin levels. Area under the plasma glucose curve, peak plasma glucose, time to peak plasma glucose and duration of plasma glucose level above baseline were significantly enhanced with increasing glucagon doses; however, these were not significantly different between 200 and 300 μg glucagon. Free fatty acids and heart rates were significantly lower initially after glucagon than after saline injection. Other haemodynamic variables, counter-regulatory hormones and side effects did not differ between interventions. Conclusions: An s.c. low-dose glucagon bolus effectively restores plasma glucose after insulin overdosing. Further research is needed to investigate whether low-dose glucagon may be an alternative treatment to oral carbohydrate intake for mild hypoglycaemia in patients with type 1 diabetes.

AB - Aim: To investigate the dose-response relationship of subcutaneous (s.c.) glucagon administration on plasma glucose and on counter-regulatory hormone responses during s.c. insulin-induced mild hypoglycaemia in patients with type 1 diabetes treated with insulin pumps. Methods: Eight insulin pump-treated patients completed a blinded, randomized, placebo-controlled study. Hypoglycaemia was induced in the fasting state by an s.c. insulin bolus and, when plasma glucose reached 3.4 mmol/l [95% confidence interval (CI) 3.2-3.5], an s.c. bolus of either 100, 200, 300 μg glucagon or saline was administered. Plasma glucose, counter-regulatory hormones, haemodynamic variables and side effects were measured throughout each study day. Peak plasma glucose level was the primary endpoint. Results: Plasma glucose level increased significantly by a mean (95% CI) of 2.3 (1.7-3.0), 4.2 (3.5-4.8) and 5.0 (4.3-5.6) mmol/l to 6.1 (4.9-7.4), 7.9 (6.4-9.3) and 8.7 (7.8-9.5) vs 3.6 (3.4-3.9) mmol/l (p < 0.001) after the three different glucagon doses as compared with saline, and the increase was neither correlated with weight nor insulin levels. Area under the plasma glucose curve, peak plasma glucose, time to peak plasma glucose and duration of plasma glucose level above baseline were significantly enhanced with increasing glucagon doses; however, these were not significantly different between 200 and 300 μg glucagon. Free fatty acids and heart rates were significantly lower initially after glucagon than after saline injection. Other haemodynamic variables, counter-regulatory hormones and side effects did not differ between interventions. Conclusions: An s.c. low-dose glucagon bolus effectively restores plasma glucose after insulin overdosing. Further research is needed to investigate whether low-dose glucagon may be an alternative treatment to oral carbohydrate intake for mild hypoglycaemia in patients with type 1 diabetes.

U2 - 10.1111/dom.12627

DO - 10.1111/dom.12627

M3 - Journal article

C2 - 26743775

SN - 1462-8902

VL - 18

SP - 410

EP - 418

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 4

ER -