Circulating levels of gut hormones in anorexia nervosa before and after short-term weight restoration

Gastrointestinal hormones such as glucagon-like peptide-1 (GLP-1), gastric inhibitory peptide (GIP), glucagon, and glicentin are important regulators of appetite and glucose homeostasis. While agonists of GLP-1 and GIP receptors are approved treatments for type 2 diabetes and obesity, their role in anorexia nervosa (AN) remains largely unknown. In this study, we measured fasting serum levels of GLP-1, GIP, glucagon, and glicentin in 80 female patients with AN before (acAN-T1) and after short-term weight restoration (acAN-T2) compared to 80 age-matched female healthy controls (HC). GIP levels were higher (42.9%) in acAN-T1 than in HC, while GLP-1, glicentin, and glucagon showed no group differences. Additionally, acAN-T1 patients exhibited lower fasting glucose (-8.4%) and insulin (-42.6%) levels than HC. In acAN-T2, GIP, GLP-1, and glicentin levels decreased (-30.4%, -9.7%, -15.7 %, respectively), with only GIP normalizing. Glucose and insulin levels increased (4.5% and 41.4%, respectively), although they remained lower than in HC. Importantly, changes in GIP levels after short-term weight restoration negatively correlated (r = -0.279) with changes in glucose levels. Furthermore, GIP levels in acAN-T1 were positively associated with disordered eating and depressive symptoms, independent of BMI-SDS. These results reveal that GIP shows a distinct pattern of dysregulation and normalization in AN and link GIP levels to both glucose metabolism and symptom severity in AN. Thus, our findings support the rationale for investigating GIP receptor-targeted therapies in AN.