TY - JOUR
T1 - Altered glucagon and GLP-1 responses to oral glucose in children and adolescents with obesity and insulin resistance
AU - Stinson, Sara Elizabeth
AU - Fernández de Retana Alzola, Ierai
AU - Brünner Hovendal, Emilie Damgaard
AU - Lund, Morten Asp Vonsild
AU - Fonvig, Cilius Esmann
AU - Holm, Louise Aas
AU - Jonsson, Anna Elisabet
AU - Frithioff-Bøjsøe, Christine
AU - Christiansen, Michael
AU - Pedersen, Oluf
AU - Ängquist, Lars
AU - Sørensen, Thorkild I A
AU - Holst, Jens Juul
AU - Hartmann, Bolette
AU - Holm, Jens-Christian
AU - Hansen, Torben
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2024/6/1
Y1 - 2024/6/1
N2 - CONTEXT: Pediatric obesity is characterized by insulin resistance, yet it remains unclear whether insulin resistance contributes to abnormalities in glucagon and incretin secretion.OBJECTIVE: To examine whether fasting and stimulated glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations differ between children and adolescents with obesity and insulin resistance (OIR), obesity and normal insulin sensitivity (OIS), and controls with normal weight (NW).METHODS: 80 (34 boys) children and adolescents, aged 7-17 years with OIR (n = 22), OIS (n = 22), and NW (n = 36) underwent an oral glucose tolerance test with measurements of serum insulin, plasma glucose, glucagon, total GLP-1, and total GIP. Homeostatic model assessment of insulin resistance (HOMA-IR), single point insulin sensitivity estimator (SPISE), Matsuda index, insulinogenic index (IGI), and oral disposition index (ODI) were calculated.RESULTS: Fasting concentrations of glucagon and GLP-1 were higher in the OIR group, with no significant differences for GIP. The OIR group had higher glucagon total area under the curve (tAUC0-120) and lower GLP-1 incremental AUC (iAUC0-120), with no significant differences in GIP iAUC0-120. Higher fasting glucagon was associated with higher HOMA-IR, lower Matsuda index, lower SPISE, higher IGI, and higher plasma alanine transaminase, whereas higher fasting GLP-1 was associated with higher HOMA-IR, lower Matsuda index, and lower ODI. Higher glucagon tAUC0-120 was associated lower SPISE and lower Matsuda index, whereas lower GLP-1 iAUC0-120 was associated with a higher HOMA-IR, lower Matsuda index, and lower ODI.CONCLUSION: Children and adolescents with OIR have elevated fasting concentrations of glucagon and GLP-1, higher glucagon and lower GLP-1 responses during an OGTT compared to those with OIS and NW. In contrast, individuals with OIS have similar hormone responses to those with NW.
AB - CONTEXT: Pediatric obesity is characterized by insulin resistance, yet it remains unclear whether insulin resistance contributes to abnormalities in glucagon and incretin secretion.OBJECTIVE: To examine whether fasting and stimulated glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations differ between children and adolescents with obesity and insulin resistance (OIR), obesity and normal insulin sensitivity (OIS), and controls with normal weight (NW).METHODS: 80 (34 boys) children and adolescents, aged 7-17 years with OIR (n = 22), OIS (n = 22), and NW (n = 36) underwent an oral glucose tolerance test with measurements of serum insulin, plasma glucose, glucagon, total GLP-1, and total GIP. Homeostatic model assessment of insulin resistance (HOMA-IR), single point insulin sensitivity estimator (SPISE), Matsuda index, insulinogenic index (IGI), and oral disposition index (ODI) were calculated.RESULTS: Fasting concentrations of glucagon and GLP-1 were higher in the OIR group, with no significant differences for GIP. The OIR group had higher glucagon total area under the curve (tAUC0-120) and lower GLP-1 incremental AUC (iAUC0-120), with no significant differences in GIP iAUC0-120. Higher fasting glucagon was associated with higher HOMA-IR, lower Matsuda index, lower SPISE, higher IGI, and higher plasma alanine transaminase, whereas higher fasting GLP-1 was associated with higher HOMA-IR, lower Matsuda index, and lower ODI. Higher glucagon tAUC0-120 was associated lower SPISE and lower Matsuda index, whereas lower GLP-1 iAUC0-120 was associated with a higher HOMA-IR, lower Matsuda index, and lower ODI.CONCLUSION: Children and adolescents with OIR have elevated fasting concentrations of glucagon and GLP-1, higher glucagon and lower GLP-1 responses during an OGTT compared to those with OIS and NW. In contrast, individuals with OIS have similar hormone responses to those with NW.
KW - Adolescent
KW - Blood Glucose/analysis
KW - Child
KW - Fasting/blood
KW - Female
KW - Gastric Inhibitory Polypeptide/blood
KW - Glucagon-Like Peptide 1/blood
KW - Glucagon/blood
KW - Glucose Tolerance Test
KW - Humans
KW - Insulin Resistance/physiology
KW - Insulin/blood
KW - Male
KW - Pediatric Obesity/blood
UR - http://www.scopus.com/inward/record.url?scp=85193564094&partnerID=8YFLogxK
U2 - 10.1210/clinem/dgad728
DO - 10.1210/clinem/dgad728
M3 - Journal article
C2 - 38087928
SN - 0021-972X
VL - 109
SP - 1590
EP - 1600
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 6
ER -