Hyperglucagonemia in Pediatric Adiposity Associates With Cardiometabolic Risk Factors but Not Hyperglycemia.

Abstract

CONTEXT:

In adults, hyperglucagonemia is associated with type 2 diabetes, impaired glucose tolerance, and obesity. The role of glucagon in pediatric overweight/obesity remains unclear.

OBJECTIVE:

We examined whether fasting concentrations of glucagon are elevated in youth with overweight/obesity and whether this associates with cardiometabolic risk profiles.

METHODS:

Analyses were based on the cross-sectional HOLBAEK study, including children and adolescents 6 to 19 years of age, with overweight/obesity from an obesity clinic group (n = 2154) and with normal weight from a population-based group (n = 1858). Fasting concentrations of plasma glucagon and cardiometabolic risk outcomes were assessed, and multiple linear and logistic regressions models were performed.

RESULTS:

The obesity clinic group had higher glucagon concentrations than the population-based group (P < 0.001). Glucagon positively associated with body mass index (BMI) standard deviation score (SDS), waist, body fat %, liver fat %, alanine transaminase (ALT), high-sensitivity C-reactive protein, homeostasis model assessment of insulin resistance, insulin, C-peptide, LDL-C, triglycerides, SDS of diastolic and systolic blood pressure, and was inversely associated with fasting glucose. The inverse relationship between glucagon and glucose was attenuated in individuals with high BMI SDS and high fasting insulin. Glucagon was associated with a higher prevalence of insulin resistance, increased ALT, dyslipidemia, and hypertension, but not with hyperglycemia. Glucagon was positively associated with fasting total glucagon-like peptide-1.

CONCLUSION:

Compared with normal weight peers, children and adolescents with overweight/obesity had elevated concentrations of fasting glucagon, which corresponded to worsened cardiometabolic risk outcomes, except for hyperglycemia. This suggests hyperglucagonemia in youth may precede impairments in glucose regulation.

• Authors: Sara E Stinson, Anna E Jonsson, Ierai Fernández de Retana Alzola, Morten A V Lund, Christine Frithioff-Bøjsøe, Louise Aas Holm, Cilius E Fonvig, Oluf Pedersen, Lars Ängquist, Thorkild I A Sørensen, Jens J Holst, Michael Christiansen, Jens-Christian Holm, Bolette Hartmann, Torben Hansen
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 107 Issue 6 Pg. 1569-1576 (05 17 2022) ISSN: 1945-7197 [Electronic] United States
• PMID: 35213713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

Chemical References

• Blood Glucose
• Insulin
• Glucagon
• Glucose

Topics

• Adiposity (physiology)
• Adolescent
• Blood Glucose (metabolism)
• Body Mass Index
• Cardiometabolic Risk Factors
• Cardiovascular Diseases (epidemiology)
• Child
• Cross-Sectional Studies
• Diabetes Mellitus, Type 2
• Glucagon
• Glucose
• Humans
• Hyperglycemia (complications, epidemiology)
• Insulin (metabolism)
• Insulin Resistance
• Overweight (complications, epidemiology)
• Pediatric Obesity (complications, epidemiology)
• Risk Factors
• Young Adult