IGF-1 and recovery in anorexia nervosa: evidence from population-based and clinical cohorts

CONTEXT: Anorexia nervosa (AN) is associated with severe metabolic and endocrine alterations, including growth hormone (GH) resistance and reduced insulin-like growth factor 1 (IGF-1). The longitudinal behavior of IGF-1 during treatment remains incompletely characterized. OBJECTIVE: To evaluate IGF-1 levels in current and weight restored AN, determine metabolic correlates, and examine longitudinal changes during clinical treatment. DESIGN: Cross-sectional analysis in a population-based cohort and longitudinal analysis in a clinical cohort. SETTING: UK Biobank (UKB) and a specialist eating disorder clinic. PARTICIPANTS: (i) UKB: 129 adult women with current AN, 2,380 weight restored AN, and 2,380 healthy controls (HC) matched for age, sex, and BMI. (ii) Clinical cohort: 189 adult women with AN assessed at baseline and 12-month follow-up. MAIN OUTCOMES MEASURES: Plasma IGF-1 levels; secondary metabolic and reproductive hormones including GH, insulin, glucose, FT3, and gonadal hormones. RESULTS: Across the UKB groups, IGF-1 levels showed a graded pattern: lowest in current AN, medium in weight restored AN, and highest in HC. In the clinical cohort, IGF-1 correlated positively with insulin, glucose, and FT3, and negatively with GH, consistent with GH resistance. IGF-1 levels increased significantly over 12 months of treatment (p = 0.003), with higher BMI at baseline predicting greater increases. Higher IGF-1 levels were associated with greater likelihood of menstrual function independent of BMI (p < 0.001). CONCLUSIONS: IGF-1 appears reduced in current AN and may only partly normalize with weight restoration. IGF-1 may reflect metabolic state and reproductive function, suggesting value as an indicator of severity and treatment response.