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
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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. / Pörksen, Sven; Nielsen, Lotte B; Kaas, Anne; Kocova, Mirjana; Chiarelli, Francesco; Orskov, Cathrine; Holst, Jens Juul; Ploug, Kenneth B; Hougaard, Philip; Hansen, Lars; Mortensen, Henrik B.
In: The Journal of clinical endocrinology and metabolism, Vol. 92, No. 8, 08.2007, p. 2910-6.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - 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
AU - Pörksen, Sven
AU - Nielsen, Lotte B
AU - Kaas, Anne
AU - Kocova, Mirjana
AU - Chiarelli, Francesco
AU - Orskov, Cathrine
AU - Holst, Jens Juul
AU - Ploug, Kenneth B
AU - Hougaard, Philip
AU - Hansen, Lars
AU - Mortensen, Henrik B
PY - 2007/8
Y1 - 2007/8
N2 - CONTEXT: 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.DESIGN: We conducted a prospective, noninterventional, 12-month follow-up study conducted in 22 centers in 18 countries.PATIENTS: Patients included 257 children and adolescents less than 16 yr old with newly diagnosed type 1 diabetes; 204 completed the 12-month follow-up.SETTING: The study was conducted at pediatric outpatient clinics.MAIN OUTCOME MEASURES: 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.CONCLUSION: 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.
AB - CONTEXT: 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.DESIGN: We conducted a prospective, noninterventional, 12-month follow-up study conducted in 22 centers in 18 countries.PATIENTS: Patients included 257 children and adolescents less than 16 yr old with newly diagnosed type 1 diabetes; 204 completed the 12-month follow-up.SETTING: The study was conducted at pediatric outpatient clinics.MAIN OUTCOME MEASURES: 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.CONCLUSION: 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.
KW - ATP-Binding Cassette Transporters
KW - Adolescent
KW - Blood Glucose
KW - C-Peptide
KW - Child
KW - Cohort Studies
KW - Diabetes Mellitus, Type 1
KW - Eating
KW - Female
KW - Glucagon
KW - Glucagon-Like Peptide 1
KW - Glucagon-Secreting Cells
KW - Hemoglobin A, Glycosylated
KW - Humans
KW - Immunohistochemistry
KW - Insulin-Secreting Cells
KW - Male
KW - Postprandial Period
KW - Potassium Channels
KW - Potassium Channels, Inwardly Rectifying
KW - Receptors, Drug
KW - Sulfonylurea Receptors
U2 - 10.1210/jc.2007-0244
DO - 10.1210/jc.2007-0244
M3 - Journal article
C2 - 17519307
VL - 92
SP - 2910
EP - 2916
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 8
ER -
ID: 132050126