Hyperglucagonemia Linked to Adverse Cardiometabolic Profiles in Pediatric Adiposity

An overweight child's stomach with a tape measure
An overweight child’s stomach with a tape measure
Investigators studied a group of children and adolescents to determine whether a relationship exists between fasting plasma glucagon levels and cardiometabolic risk outcomes.

Children and adolescents who are overweight or obese were found to demonstrate hyperglucagonemia, which correlated with worse cardiometabolic risk factors except hyperglycemia, according to the results of a study published in the Journal of Clinical Endocrinology & Metabolism.

Investigators analyzed data from 2154 children and adolescents between 6 and 19 years of age who were overweight or obese and treated at a Danish obesity clinic. They compared outcomes with 1858 individuals of similar ages who were of normal weight.

Outcome measures included fasting plasma glucagon levels and cardiometabolic risk factors such as body mass index (BMI), waist circumference, body fat percentage, liver fat percentage, alanine transaminase (ALT), C-peptide, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, insulin, insulin resistance, glycated hemoglobin (HbA1C), high-sensitivity C-reactive protein, fasting glucose, and systolic and diastolic blood pressures.

The obesity clinic group demonstrated higher glucagon concentrations than the group of normal weight (median 7.8 vs 5.5 pmol/L; P <.001). The researchers found that glucagon levels corresponded positively with most cardiometabolic risk factors with the exception of fasting glucose levels, which exhibited an inverse relationship with glucagon. Glucagon levels especially correlated with higher incidence of insulin resistance, dyslipidemia, hypertension, increased ALT, and fasting total glucagon-like peptide-1 (GLP-1) levels. Glucagon did not demonstrate statistically significant associations with high-density lipoprotein cholesterol or HbA1C.

“These findings demonstrate that fasting glucagon is an indicator of adverse cardiometabolic risk traits in children and adolescents with overweight/obesity but does not associate with hyperglycemia in this age group,” the authors said. “Higher fasting concentrations of glucagon are also present in adults with obesity and normal glucose tolerance, suggesting that hyperglucagonemia manifests early in the development of glucose intolerance.”

Limitations of the study include the inability to assess temporality of overweight/obesity progression due to single-point-in-time collection of outcome measurements, as well as the inability to establish causality due to the cross-sectional study design.


Stinson SE, Jonsson AE, Fernández de Retana Alzola I, et al. Hyperglucagonemia in pediatric adiposity associates with cardiometabolic risk factors but not hyperglycemia. J Clin Endocrinol Metab. Published online February 25, 2022. doi:10.1210/clinem/dgac108