Fasting Plasma GLP-1 Is Associated With Overweight/Obesity and Cardiometabolic Risk Factors in Children and Adolescents

Abstract

Context The importance of fasting GLP-1 in altered metabolic outcomes has been questioned. Objective To assess if fasting GLP-1 differs in children and adolescents with overweight/obesity compared to a population-based reference, and whether concentrations predict cardiometabolic risk (CMR) factors. Methods Analyses were based on The Danish Childhood Obesity Data- and Biobank, a cross-sectional study including children and adolescents, 6-19 years old, from an obesity clinic group (n = 1978) and from a population-based group (n = 2334). Fasting concentrations of plasma total GLP-1 and quantitative CMR factors were assessed. The effects of GLP-1 as a predictor of CMR risk outcomes were examined by multiple linear and logistic regression modelling. Results The obesity clinic group had higher fasting GLP-1 concentrations (median 3.3 pmol/L; interquartile range 2.3–4.3) than the population-based group (2.8 pmol/L; 2.1–3.8; P < 2.2E-16). BMI SDS, waist circumference and total body fat percentage were significant predictors of fasting GLP-1 concentrations in boys and girls. Fasting GLP-1 concentrations positively associated with HOMA-IR, fasting values of insulin, hs-CRP, C-peptide, triglycerides, ALT, HbA1c and SDS of diastolic and systolic blood pressure. A 1-SD increase in fasting GLP-1 associated with an increased risk of insulin resistance (Odds ratio [OR] 1.59), dyslipidemia (OR 1.16), increased ALT (OR 1.14), hyperglycemia (OR 1.12) and hypertension (OR 1.12). Conclusions Overweight/obesity in children and adolescents is associated with increased fasting plasma total GLP-1 concentrations, which was predictive of higher cardiometabolic risk factors.

The Association between Peptide Hormones with Obesity and Insulin Resistance Markers in Lean and Obese Individuals in the United Arab Emirates

“…We found that fasting GLP-1 was significantly higher in obese participants, as seen elsewhere [ 39 , 40 ]. Notably, GLP-1 was the only independent gut peptide predictor of obesity markers and IR.…”

“…This suggestion is plausible, as overfeeding was shown to increase fasting levels of GLP-1 [ 42 ]. Obesity is also associated with intestinal microbiota dysbiosis, altering GLP-1 secretion [ 40 ]. Our findings seem to be aligned with the emerging literature [ 40 , 41 ], whereby fasting GLP-1 may be considered an indicator of cardiometabolic risk.…”

“…Obesity is also associated with intestinal microbiota dysbiosis, altering GLP-1 secretion [ 40 ]. Our findings seem to be aligned with the emerging literature [ 40 , 41 ], whereby fasting GLP-1 may be considered an indicator of cardiometabolic risk. Most importantly, these findings suggest therapeutic implications.…”

Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation

“…An enhanced GLP-1-secretion may, according to both in vitro and rodent studies, be mediated by toll-like receptors at the basolateral sides of the L-cells, which become exposed to endotoxins due to mucosal barrier disruption ( 16 , 46 , 47 ). Such mechanisms might be active in critically ill patients where fasting GLP-1 levels have been found elevated ( 25 , 47 ). In this study, GLP-1 levels in the patients, including pre-transplant levels, were generally higher than in healthy controls, suggesting that similar mechanisms may, to some extent, be activated already at the timepoint of referral in these often severely affected patients.…”

“…A control cohort matched by sex and nearest age option with a patient/control frequency ratio of 1:5 (N = 410 controls, Table 2 ) was included from a population-based cohort of Danish/North-European children and adolescents without obesity and diabetes, 6-18 years of age (N = 2,266), enrolled in The Danish Childhood Obesity Data- and Biobank from 2009 - 2019 and previously described ( 24 , 25 ).…”