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 6-19-year-old children and adolescents with overweight/obesity from an obesity clinic group (n = 2154) and a population-based group with normal weight (n = 1858). Fasting concentrations of plasma glucagon and cardiometabolic risk outcomes were assessed, 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 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. Conclusions Compared to 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.

The relationship between glucose and the liver-alpha cell axis – A systematic review

“…While fasting glucagon was associated with cardiometabolic risk markers (e.g., BMI SDS, body fat percentage, liver fat percentage, triglycerides, blood pressure), it was not associated with hyperglycemia. Thus, hyperglucagonemia might precede impairments in glucose regulation ( 160 ). This finding is in line with the pediatric data from the RISE study ( 71 ).…”

Helicobacter pyloriseropositivity associates with hyperglycemia, but not obesity in Danish children and adolescents

“…We used a random subset of individuals from The HOLBAEK Study, that has been described elsewhere (55,56). Briefly, serum samples derived from two groups of children and adolescents: (a) an obesity clinic group (n = 713) consisting of individuals with a BMI SDS > 90th percentile (BMI SDS > 1.28) according to Danish reference values (57), who followed a multifaceted childhood obesity management program at Holbæk Hospital and (b) a population-based reference group (n = 990) consisting of subjects recruited from schools in the same geographical area.…”

“…The study participants have been thoroughly characterized in relation to their age, sex, socioeconomic status and various cardiometabolic risk factors. The characteristics of the full obesity clinic and population-based cohorts have been described elsewhere (56). In brief, the study groups did not differ in age, but there were more boys in the obesity-clinic cohort (45.8%) than in the population-based cohort (40.3%).…”

“…We used a random subset of individuals from The HOLBAEK Study, that has been described elsewhere (55,56). Briefly, serum samples derived from two groups of children and elsewhere (56).…”

An adult‐based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents

“…Venous blood samples were collected after an overnight fasting. Fasting biochemical measurements including in plasma: ALT, aspartate transaminase (AST), gammaglutamyltransferase (GGT), lactate dehydrogenase (LDH), bilirubin, 27 high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), triglycerides (TG), 28 glucose, 22 total glucagon‐like peptide‐1 (GLP‐1), 21 and glucagon, 29 in serum: insulin, C‐peptide, 22 hs‐CRP, 30 and in whole blood HbA1c, 22 total white blood cells (WBC), 30 as previously described.…”