Altered glucagon and GLP-1 responses to oral glucose in children and adolescents with obesity and insulin resistance

Sara Elizabeth Stinson, Ierai Fernández de Retana Alzola, Emilie Damgaard Brünner Hovendal, Morten Asp Vonsild Lund, Cilius Esmann Fonvig, Louise Aas Holm, Anna Elisabet Jonsson, Christine Frithioff-Bøjsøe, Michael Christiansen, Oluf Pedersen, Lars Ängquist, Thorkild I.A. Sørensen, Jens Juul Holst, Bolette Hartmann, Jens-Christian Holm*, Torben Hansen*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstract

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.

OriginalsprogEngelsk
Sider (fra-til)1590-1600
Antal sider11
TidsskriftThe Journal of clinical endocrinology and metabolism
Vol/bind109
Udgave nummer6
Tidlig onlinedato13 dec. 2023
DOI
StatusUdgivet - 17 maj 2024

Bibliografisk note

© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.

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