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- Biochemistry (medical)
- Clinical Biochemistry
- Endocrinology
- Biochemistry
- Endocrinology, Diabetes and Metabolism
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, 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.