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.


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.
Brown
Rebecca J
RJ
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA. brownrebecca@mail.nih.gov
Sinaii
Ninet
N
Rother
Kristina I
KI
D000293:Adolescent; D017668:Age of Onset; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004435:Eating; D005215:Fasting; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000503:physiopathology*; D008297:Male
D002096:C-Peptide; D007328:Insulin; D005934:Glucagon