Too much glucagon, too little insulin: time course of pancreatic islet dysfunction in new-onset type 1 diabetes

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 beta-cell function.

Figure 1—

Glucagon secretion after a mixed meal (A) and glucagon and C-peptide AUC after a mixed meal (B) during the first year after diagnosis of type 1 diabetes. Data are means ± SEM.