Meal-stimulated glucagon release is associated with postprandial blood glucose level and does not interfere with glycemic control in children and adolescents with new-onset type 1 diabetes.
BACKGROUND
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
Our objective was to investigate the relationship between postprandial glucose and glucagon level during the first 12 months after diagnosis of childhood type 1 diabetes.


METHODS
We conducted a prospective, noninterventional, 12-month follow-up study conducted in 22 centers in 18 countries.


METHODS
Patients included 257 children and adolescents less than 16 yr old with newly diagnosed type 1 diabetes; 204 completed the 12-month follow-up.


METHODS
The study was conducted at pediatric outpatient clinics.


METHODS
We assessed residual beta-cell function (C-peptide), glycosylated hemoglobin (HbA(1c)), blood glucose, glucagon, and glucagon-like peptide-1 (GLP-1) release in response to a 90-min meal stimulation (Boost) at 1, 6, and 12 months after diagnosis.


RESULTS
Compound symmetric repeated-measurements models including all three visits showed that postprandial glucagon increased by 17% during follow-up (P = 0.001). Glucagon levels were highly associated with postprandial blood glucose levels because a 10 mmol/liter increase in blood glucose corresponded to a 20% increase in glucagon release (P = 0.0003). Glucagon levels were also associated with GLP-1 release because 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.


CONCLUSIONS
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.
Pörksen
Sven
S
Department of Pediatrics, Forskerparken, Glostrup University Hospital, DK-2600 Glostrup, Denmark. svepor01@glo.regionh.dk
Nielsen
Lotte B
LB
Kaas
Anne
A
Kocova
Mirjana
M
Chiarelli
Francesco
F
Orskov
Cathrine
C
Holst
Jens J
JJ
Ploug
Kenneth B
KB
Hougaard
Philip
P
Hansen
Lars
L
Mortensen
Henrik B
HB
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D004435:Eating / Q000502:physiology*; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D050416:Glucagon-Secreting Cells / Q000502:physiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D019518:Postprandial Period / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D002096:C-Peptide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human