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: To investigate the relationship between postprandial glucose and glucagon level during the first 12 months after diagnosis of childhood type 1 diabetes.

Design: Prospective, non-interventional, 12 months follow-up study conducted in 22 centers in 18 countries.

Patients: 257 children and adolescents < 16 years with newly diagnosed type 1 diabetes. 204 completed the 12 months follow-up.

Setting: Pediatric outpatient clinic.

Main outcome measures: Residual beta cell function (C-peptide), HbA_1c, blood glucose, glucagon- and GLP-1 release in response to a 90 minute meal stimulation (BOOST) at 1, 6, and 12 months after diagnosis.

Results: Compound symmetric repeated measurements models including all 3 visits showed: Postprandial glucagon increased by 17% during follow up (P=0.001). Glucagon levels were highly associated with postprandial blood glucose levels as a 10 mmol/L increase in blood glucose corresponded to 20% increase in glucagon release (p=0.0003). Glucagon levels were also associated with GLP-1 release as 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.