Glucagon-Like Peptide-2 as a Potential Biomarker for Nonalcoholic Fatty Liver Disease in Children with Obesity: Preliminary Assessment of Metabolic Associations and Underlying Mechanisms.

Objective: This study aimed to investigate the effects of glucagon-like peptide-2 (GLP-2) on insulin resistance and lipid metabolism, as well as potential mechanisms contributing to the development of non-alcoholic fatty liver disease (NAFLD) in children with obesity.

Methods: A cross-sectional study was conducted involving 107 children with obesity, aged between 5 and 15 years, including 55 with NAFLD and 52 without NAFLD. Anthropometric assessments and fasting blood samples were collected to evaluate GLP-2, plasma glucose, insulin (INS), lipids, leptin (LEP), and adiponectin (ADPN). Correlation and logistic regression analyses were performed to evaluate associations between GLP-2 and metabolic parameters.

Results: Children with NAFLD exhibited significantly higher levels of GLP-2, LEP, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FPG), INS, and the homeostasis model assessment of insulin resistance index (HOMA-IR) (all p<0.05), along with significantly lower levels of ADPN and high-density lipoprotein cholesterol (HDL-C) compared with those without NAFLD (p<0.05). GLP-2 concentrations correlated positively with TC (r=0.42), TG (r=0.51), LDL-C (r=0.38), FPG (r=0.61), INS (r=0.58), HOMA-IR (r=0.61), and LEP (r=0.42), and negatively with ADPN (r=-0.53; all p<0.01). In univariate analysis, GLP-2 was identified as a risk factor for NAFLD (odds ratio [OR]=1.225, 95% confidence interval [CI]: 1.001-1.499, p<0.05); however, the association was attenuated after adjustment for body mass index (OR=1.112, p=0.102). ADPN retained a protective association (OR=0.771, p<0.05).

Conclusion: GLP-2 may contribute to the pathophysiology of insulin resistance and dyslipidemia in pediatric NAFLD, potentially via modulation of adipokine activity. These findings suggest GLP-2 as a candidate biomarker and possible therapeutic target in this population.