Too Much Glucagon, Too Little Insulin
Time course of pancreatic islet dysfunction in new-onset type 1 diabetes
- Rebecca J. Brown, MD1,
- Ninet Sinaii, PHD, MPH2 and
- Kristina I. Rother, MD, MHSC1
- 1National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
- 2National Institutes of Health, Clinical Center, Bethesda, Maryland
- Corresponding author: Rebecca J. Brown, brownrebecca{at}mail.nih.gov
Abstract
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 β-cell function.
Footnotes
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- Accepted April 10, 2008.
- Received March 21, 2008.
- DIABETES CARE
