medwireNews: Research shows that postprandial glucagon levels increase over time in children with newly diagnosed Type 1 diabetes, and are associated with worsening glycaemic control, suggesting an adjunctive treatment approach.

Glucagon levels rose by 51% within the first year of follow-up, and by 160% at 5 years, say Siri Fredheim (Herlev Hospital, Copenhagen, Denmark) and study co-authors.

“Notably, hyperglucagonaemia in response to liquid mixed-meal feeding is evidently established shortly after disease onset and seems to persist after several years with diabetes”, they write in Diabetologia.

The team obtained the results in 129 children, aged an average of 10 years at the time of diagnosis, who were initially in partial remission (postprandial C-peptide >300 pmol/L). All children underwent a liquid mixed-meal test at 1, 3, 6 and 12 months after diagnosis, and 40 were also tested at 60 months.

During this time, the number of children in partial remission fell from 71% at 6 months to 48% at 12 months and 5% at 5 years. Postprandial plasma glucose levels rose by 38% over the first 12 months and 68% over the full follow-up, while glycated haemoglobin (HbA1c) levels fell sharply over the first 3 months but then rose steadily.

Glucagon-like protein (GLP)-1 levels rose by a significant 10% during the first 12 months of the study and by a nonsignificant 10% over the entire follow-up.

Postprandial glucagon levels were positively associated with older age at diagnosis and with male gender, but not with body mass index. They rose by 21% with each doubling of plasma glucose and by 33% with each doubling of GLP-1 levels over the whole study period.

The researchers note that GLP-1 is known to have a suppressive effect on glucagon, and say that the association found in their study “may indicate that the secretion of both GLP-1 and glucagon in type 1 diabetes is influenced by factors that outweigh their normal mutual interaction.”

Glucagon was significantly associated with glycaemic control, such that each doubling in glucagon levels corresponded to a 3% relative increase in HbA1c levels. This association was independent of C-peptide levels above 300 pmol/L, indicating that it was an effect of the presence of children with residual beta cell function.

“The association of hyperglucagonaemia with GLP-1 and impaired glycaemic control suggests that GLP-1 in physiological doses is not sufficient to suppress glucagon”, conclude Fredheim et al. “GLP-1 analogues as add-on therapy to insulin early in the course of type 1 diabetes should be investigated in further studies.”

By Eleanor McDermid, Senior medwireNews Reporter

Diabetologia 2014; Advance online publication

Free abstract