title: Meal-stimulated glucagon release is associated with postprandial blood glucose level and does not interfere with glycemic control in children and adolescents with new-onset type 1 diabetes.
abstract: BACKGROUND
  The role of glucagon in hyperglycemia in type 1 diabetes is unresolved, and in vitro studies suggest that increasing blood glucose might stimulate glucagon secretion.
  
  
  OBJECTIVE
  Our objective was to investigate the relationship between postprandial glucose and glucagon level during the first 12 months after diagnosis of childhood type 1 diabetes.
  
  
  METHODS
  We conducted a prospective, noninterventional, 12-month follow-up study conducted in 22 centers in 18 countries.
  
  
  METHODS
  Patients included 257 children and adolescents less than 16 yr old with newly diagnosed type 1 diabetes; 204 completed the 12-month follow-up.
  
  
  METHODS
  The study was conducted at pediatric outpatient clinics.
  
  
  METHODS
  We assessed residual beta-cell function (C-peptide), glycosylated hemoglobin (HbA(1c)), blood glucose, glucagon, and glucagon-like peptide-1 (GLP-1) release in response to a 90-min meal stimulation (Boost) at 1, 6, and 12 months after diagnosis.
  
  
  RESULTS
  Compound symmetric repeated-measurements models including all three visits showed that postprandial glucagon increased by 17% during follow-up (P = 0.001). Glucagon levels were highly associated with postprandial blood glucose levels because a 10 mmol/liter increase in blood glucose corresponded to a 20% increase in glucagon release (P = 0.0003). Glucagon levels were also associated with GLP-1 release because a 10% increase in GLP-1 corresponded to a 2% increase in glucagon release (P = 0.0003). Glucagon levels were not associated (coefficient -0.21, P = 0.07) with HbA(1c), adjusted for insulin dose. Immunohistochemical staining confirmed the presence of Kir6.2/SUR1 in human alpha-cells.
  
  
  CONCLUSIONS
  Our study supports the recent in vitro data showing a stimulation of glucagon secretion by high glucose levels. Postprandial glucagon levels were not associated with HbA(1c), adjusted for insulin dose, during the first year after onset of childhood type 1 diabetes.
authors.affiliation: Department of Pediatrics, Forskerparken, Glostrup University Hospital, DK-2600 Glostrup, Denmark. svepor01@glo.regionh.dk
authors.forename: Sven
authors.initials: S
authors.lastname: Pörksen
authors.forename: Lotte B
authors.initials: LB
authors.lastname: Nielsen
authors.forename: Anne
authors.initials: A
authors.lastname: Kaas
authors.forename: Mirjana
authors.initials: M
authors.lastname: Kocova
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
authors.forename: Cathrine
authors.initials: C
authors.lastname: Orskov
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Ploug
authors.forename: Philip
authors.initials: P
authors.lastname: Hougaard
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Mortensen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D004435:Eating / Q000502:physiology*; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D050416:Glucagon-Secreting Cells / Q000502:physiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D019518:Postprandial Period / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D002096:C-Peptide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human