The influence of glucagon on postprandial hyperglycaemia in children 5 years after onset of type 1 diabetes

Abstract

Aims/hypothesis: The influence of glucagon on glycaemic control in type 1 diabetes is debated. We investigated the relationship between postprandial glucagon levels and HbA1c during a period up to 60 months after diagnosis of childhood type 1 diabetes.

Methods: The Danish remission phase cohort comprised 129 children (66 boys) with type 1 diabetes whose mean (SD) age at onset was 10.0 (3.9) years. Liquid mixed-meal tests were performed prospectively at 1, 3, 6 and 12 months and a subset of 40 patients completed follow-up at 60 months. Postprandial (90 min) plasma levels of glucagon, glucose (PG), C-peptide, total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and HbA1c were analysed. Multivariate regression (repeated measurements with all five visits included) was applied and results expressed as relative change (95% CI).

Results: Postprandial glucagon levels increased 160% from 1 to 60 months after diagnosis (p < 0.0001). A doubling in postprandial PG corresponded to a 21% increase in postprandial glucagon levels (p = 0.0079), whereas a doubling in total GLP-1 levels corresponded to a 33% increase in glucagon levels (p < 0.0001). Postprandial glucagon associated negatively with postprandial C-peptide (p = 0.017). A doubling in postprandial glucagon corresponded to a 3% relative increase in HbA1c levels (p = 0.0045).

Conclusions/interpretation: Postprandial glucagon levels were associated with deterioration of glycaemic control and declining beta cell function in the first 5 years after diagnosis of type 1 diabetes. The positive association of glucagon with total GLP-1 and PG suggests that physiological regulation of alpha cell secretion in type 1 diabetes is seriously disturbed.