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

J Clin Endocrinol Metab. 2007 Aug;92(8):2910-6. doi: 10.1210/jc.2007-0244. Epub 2007 May 22.

Abstract

Context: 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.

Design: We conducted a prospective, noninterventional, 12-month follow-up study conducted in 22 centers in 18 countries.

Patients: Patients included 257 children and adolescents less than 16 yr old with newly diagnosed type 1 diabetes; 204 completed the 12-month follow-up.

Setting: The study was conducted at pediatric outpatient clinics.

Main outcome measures: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Adolescent
  • Blood Glucose / metabolism*
  • C-Peptide / metabolism
  • Child
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Eating / physiology*
  • Female
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Secreting Cells / physiology
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Immunohistochemistry
  • Insulin-Secreting Cells / physiology
  • Male
  • Postprandial Period / physiology*
  • Potassium Channels / metabolism
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Receptors, Drug / metabolism
  • Sulfonylurea Receptors

Substances

  • ABCC8 protein, human
  • ATP-Binding Cassette Transporters
  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Kir6.2 channel
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Glucagon-Like Peptide 1
  • Glucagon