title: The influence of glucagon on postprandial hyperglycaemia in children 5 years after onset of type 1 diabetes.
abstract: OBJECTIVE
  The influence of glucagon on glycaemic control in type 1 diabetes is debated. We investigated the relationship between postprandial glucagon levels and HbA1c during a period up to 60 months after diagnosis of childhood type 1 diabetes.
  
  
  METHODS
  The Danish remission phase cohort comprised 129 children (66 boys) with type 1 diabetes whose mean (SD) age at onset was 10.0 (3.9) years. Liquid mixed-meal tests were performed prospectively at 1, 3, 6 and 12 months and a subset of 40 patients completed follow-up at 60 months. Postprandial (90 min) plasma levels of glucagon, glucose (PG), C-peptide, total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and HbA1c were analysed. Multivariate regression (repeated measurements with all five visits included) was applied and results expressed as relative change (95% CI).
  
  
  RESULTS
  Postprandial glucagon levels increased 160% from 1 to 60 months after diagnosis (p < 0.0001). A doubling in postprandial PG corresponded to a 21% increase in postprandial glucagon levels (p = 0.0079), whereas a doubling in total GLP-1 levels corresponded to a 33% increase in glucagon levels (p < 0.0001). Postprandial glucagon associated negatively with postprandial C-peptide (p = 0.017). A doubling in postprandial glucagon corresponded to a 3% relative increase in HbA1c levels (p = 0.0045).
  
  
  CONCLUSIONS
  Postprandial glucagon levels were associated with deterioration of glycaemic control and declining beta cell function in the first 5 years after diagnosis of type 1 diabetes. The positive association of glucagon with total GLP-1 and PG suggests that physiological regulation of alpha cell secretion in type 1 diabetes is seriously disturbed.
authors.affiliation: Department of Pediatrics, Herlev Hospital, Herlev Ringvej 75, Arkaden, Opgang 115, Herlev, 2730, Copenhagen, Denmark, sirifredheim@dadlnet.dk.
authors.forename: Siri
authors.initials: S
authors.lastname: Fredheim
authors.forename: Marie-Louise M
authors.initials: ML
authors.lastname: Andersen
authors.forename: Sven
authors.initials: S
authors.lastname: Pörksen
authors.forename: Lotte B
authors.initials: LB
authors.lastname: Nielsen
authors.forename: Christian
authors.initials: C
authors.lastname: Pipper
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Jane
authors.initials: J
authors.lastname: Thomsen
authors.forename: Jesper
authors.initials: J
authors.lastname: Johannesen
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Mortensen
authors.forename: Jannet
authors.initials: J
authors.lastname: Svensson
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon / Q000097:blood*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000175:diagnosis; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005934:Glucagon; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human