Altered glucagon and GLP-1 responses to oral glucose in children and adolescents with obesity and insulin resistance
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Altered glucagon and GLP-1 responses to oral glucose in children and adolescents with obesity and insulin resistance. / Stinson, Sara Elizabeth; Fernández de Retana Alzola, Ierai; Brünner Hovendal, Emilie Damgaard; Lund, Morten Asp Vonsild; Fonvig, Cilius Esmann; Holm, Louise Aas; Jonsson, Anna Elisabet; Frithioff-Bøjsøe, Christine; Christiansen, Michael; Pedersen, Oluf; Ängquist, Lars; Sørensen, Thorkild I A; Holst, Jens Juul; Hartmann, Bolette; Holm, Jens-Christian; Hansen, Torben.
In: The Journal of clinical endocrinology and metabolism, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2024
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, GLP-1, and 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 for 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.CONCLUSIONS: The OIR-group had elevated fasting concentrations of glucagon and GLP-1, and higher glucagon, but lower GLP-1 responses during an OGTT compared to the OIS- and NW-groups. In contrast, the OIS-group had similar hormone responses to the NW-group.
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, GLP-1, and 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 for 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.CONCLUSIONS: The OIR-group had elevated fasting concentrations of glucagon and GLP-1, and higher glucagon, but lower GLP-1 responses during an OGTT compared to the OIS- and NW-groups. In contrast, the OIS-group had similar hormone responses to the NW-group.
U2 - 10.1210/clinem/dgad728
DO - 10.1210/clinem/dgad728
M3 - Journal article
C2 - 38087928
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
ER -
ID: 379060153