Monday, July 21, 2008

Too Much Glucagon, Too Little Insulin: Time course of pancreatic islet dysfunction in new-onset type 1 diabetes

OBJECTIVE: To determine the time course of changes in glucagon and insulin secretion in children with recently diagnosed type 1 diabetes.

RESEARCH DESIGN AND METHODS: Glucagon and C-peptide concentrations were determined in response to standard mixed meals in 23 patients with type 1 diabetes aged 9.4 +/- 4.6 years, beginning within 6 weeks of diagnosis, and every 3 months thereafter for 1 year.

RESULTS: Glucagon secretion in response to a physiologic stimulus (mixed meal) increased by 37% over 12 months, while C-peptide secretion declined by 45%. Fasting glucagon concentrations remained within the normal (nondiabetic) reference range.

CONCLUSIONS: Postprandial hyperglucagonemia worsens significantly during the first year after diagnosis of type 1 diabetes and may represent a distinct therapeutic target. Fasting glucagon values may underestimate the severity of hyperglucagonemia. The opposing directions of abnormal glucagon and C-peptide secretion over time support the link between dysregulated glucagon secretion and declining [beta]-cell function.

(C) 2008 by the American Diabetes Association, Inc.