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

TY - JOUR

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

SN - 0021-972X

VL - 92

SP - 2910

EP - 2916

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 8

ER -