Circulating IGF-1 levels and 27 digestive diseases: 461,401 UK biobank prospective analysis

Insulin-like growth factor-1 (IGF-1) regulates gastrointestinal mucosal repair, hepatocyte function, and metabolic homeostasis, but its association with a broad spectrum of digestive diseases remains unsystematic. We analyzed 461,401 UK Biobank participants (aged 40-69 years) with baseline IGF-1 measurements (stratified into quartiles: Q1 ≤ 17.525, Q2 17.526-21.253, Q3 21.254-24.825, Q4 ≥ 24.826 nmol/L) and followed up to August 2024 (median: 66-184 months). Cox proportional hazards regression and restricted cubic spline (RCS) analyses assessed associations between IGF-1 and 27 ICD-10-classified digestive diseases. Cox proportional hazards regression models confirmed inverse associations between IGF-1 levels and 17 diseases. RCS analysis uncovered key non-linear relationships between IGF-1 levels and disease risk: excessively high IGF-1 levels were associated with an elevated risk of ventral hernia, paralytic ileus and intestinal obstruction without hernia, diverticular disease of the intestine, and haemorrhoids; inguinal hernia exhibited a non-linear positive correlation with IGF-1 levels; and IGF-1 deficiency contributed to an increased risk of 19 diseases.