Elevation of Fasting GLP-1 Levels in Child and Adolescent Obesity: Friend or Foe?

Glucagon-like peptide-1 (GLP-1) receptor agonists have been gaining much attention as a therapeutic approach to type 2 diabetes and obesity. Stinson et al recently reported that fasting GLP-1 is higher in children and adolescents with overweight/obesity and that it associates with cardiometabolic risk factors in a cross-sectional study comprising more than 4000 subjects. Obvious questions include why fasting GLP-1 is significantly increased in children and adolescents with overweight/obesity and why this is correlated with cardiometabolic risks. It has been shown that the inflammatory cytokine interleukin-6 (IL-6) stimulates GLP-1 secretion from pancreatic α-cells. IL-6-induced GLP-1 secretion could therefore play a role in expanding the β-cell reservoir in compensation for increased insulin needs due to exacerbation of insulin resistance. On the other hand, augmented GLP-1 secretion leads to increased insulin secretion, thereby enhancing hepatic lipogenesis and stimulating adipogenesis, which might underlie the associations of fasting GLP-1 with % body fat, triglycerides, and alanine aminotransferase. It is also possible that GLP-1 levels are naturally increased to oppose body weight gain to maintain body weight. However, it is important to note the differing biological effects of GLP-1 at physiological and pharmacological levels, which are evident in body weight reduction by GLP-1 receptor agonists and DPP-4 inhibitors. The Stinson study clearly demonstrated that fasting GLP-1 associates with overweight/obesity and cardiometabolic risk factors in children and adolescents. However, additional experiments need to be carried out to fully understand the relevance of these observations to human disease and health.