The influence of glucagon on postprandial hyperglycaemia in children 5 years after onset of type 1 diabetes
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The influence of glucagon on postprandial hyperglycaemia in children 5 years after onset of type 1 diabetes. / Fredheim, Siri; Andersen, Marie-Louise M; Pörksen, Sven; Nielsen, Lotte B; Pipper, Christian; Hansen, Lars; Holst, Jens Juul; Thomsen, Jane; Johannesen, Jesper; Mortensen, Henrik B; Svensson, Jannet.
In: Diabetologia, Vol. 58, No. 4, 2015, p. 828-34.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The influence of glucagon on postprandial hyperglycaemia in children 5 years after onset of type 1 diabetes
AU - Fredheim, Siri
AU - Andersen, Marie-Louise M
AU - Pörksen, Sven
AU - Nielsen, Lotte B
AU - Pipper, Christian
AU - Hansen, Lars
AU - Holst, Jens Juul
AU - Thomsen, Jane
AU - Johannesen, Jesper
AU - Mortensen, Henrik B
AU - Svensson, Jannet
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.1007/s00125-014-3486-3
DO - 10.1007/s00125-014-3486-3
M3 - Journal article
C2 - 25541633
VL - 58
SP - 828
EP - 834
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 4
ER -
ID: 132046764