TY - JOUR
T1 - Hyperglucagonemia in pediatric adiposity associates with cardiometabolic risk factors but not hyperglycemia
AU - Stinson, Sara Elizabeth
AU - Jonsson, Anna E
AU - Fernández de Retana Alzola, Ierai
AU - Lund, Morten A V
AU - Frithioff-Bøjsøe, Christine
AU - Holm, Louise Aas
AU - Fonvig, Cilius E
AU - Pedersen, Oluf
AU - Ängquist, Lars
AU - Sørensen, Thorkild I.A.
AU - Holst, Jens Juul
AU - Christiansen, Michael
AU - Holm, Jens-Christian
AU - Hartmann, Bolette
AU - Hansen, Torben
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2022/5/17
Y1 - 2022/5/17
N2 - 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.
AB - 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.
KW - Adiposity/physiology
KW - Adolescent
KW - Blood Glucose/metabolism
KW - Body Mass Index
KW - Cardiometabolic Risk Factors
KW - Cardiovascular Diseases/epidemiology
KW - Child
KW - Cross-Sectional Studies
KW - Diabetes Mellitus, Type 2
KW - Glucagon
KW - Glucose
KW - Humans
KW - Hyperglycemia/complications
KW - Insulin Resistance
KW - Insulin/metabolism
KW - Overweight/complications
KW - Pediatric Obesity/complications
KW - Risk Factors
KW - Young Adult
U2 - 10.1210/clinem/dgac108
DO - 10.1210/clinem/dgac108
M3 - Article
C2 - 35213713
SN - 0021-972X
VL - 107
SP - 1569
EP - 1576
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 6
ER -