title: Effects of subcutaneous, low-dose glucagon on insulin-induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Danish Diabetes Academy, Odense, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Ranjan
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Danish Diabetes Academy, Odense, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Nørgaard
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005934:Glucagon / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007329:Insulin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D061267:Insulin Aspart / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007329:Insulin Antagonists; D005934:Glucagon; D061267:Insulin Aspart
keywords: blood pressure; counter-regulation; dose-response relationship; glucagon; heart rate; hypoglycaemia; pharmacodynamics; phrmakokinetics; side effects; type 1 diabetes