Exploring appetite-related biomarkers in anorexia nervosa during treatment: associations with diet and comparison with healthy controls

Abstract Background Nutritional treatment is a cornerstone in treatment of anorexia nervosa (AN). However, the interplay between diet and appetite hormones in the gut-brain axis remains poorly understood in AN, particularly during treatment. This study assessed the effects of 12-week inpatient treatment on appetite-related biomarker profiles in patients with AN, compared these profiles with healthy controls (HCs), and explored associations between appetite-related biomarkers, clinical characteristics and diet. Methods In this exploratory study, we included 42 patients with AN undergoing inpatient treatment and 42 age-matched HCs from the Norwegian Microbiota Study in AN (NORMA). Data was collected at baseline, after 6 and 12 weeks of treatment for patients with AN, and at baseline for HCs. Appetite-related biomarkers were measured in serum using Luminex technology and dietary intake was recorded via a 3-day digital food diary/interview. Statistical analyses included group comparisons, regression models, mixed-effects models, and correlation analyses. Results Compared to HCs, patients exhibited significantly lower levels of adipsin, leptin, insulin, and resistin, and higher levels of adiponectin and glucose-dependent insulinotropic polypeptide (GIP) at baseline, with a trend for ghrelin ( p = 0.08). Group differences in glucagon-like-peptide-1 (GLP-1) and glucagon were higher in older patients. No baseline differences were observed for C-peptide, plasminogen activator inhibitor-1, or visfatin. After 12 weeks, mean BMI had increased significantly in patients with AN from 15.5 to 18.2 kg/m², adipsin, leptin, insulin, and C-peptide increased while ghrelin decreased and approached that of HCs. Glucagon, adiponectin, GIP, and GLP-1 were largely resistant to change. Notably, BMI alone did not fully account for biomarker differences; dietary composition, particularly fiber and fat, appeared important for hormone regulation in AN. Conclusion Prior to treatment, appetite-related biomarkers differed markedly between patients with AN and HCs. Although inpatient treatment increased body weight and normalized several biomarkers, BMI for most patients with AN remained below the healthy range and several biomarkers displayed limited responsiveness to treatment, suggesting continued gut–brain axis dysregulation. Whether it is possible to target unresponsive hormones by nutritional and/or pharmacological therapies to improve treatment success of AN remains to be investigated. Trial registration clinicaltrials.gov, NCT06144905, registered Sep 22, 2023