Circulating IGF-1 levels show complex, non-linear associations with 27 digestive diseases in a large UK Biobank cohort
Background
Insulin-like growth factor-1 (IGF-1) is a critical endocrine hormone, primarily produced by the liver, that mediates many of the effects of growth hormone. It plays a fundamental role in cell growth, differentiation, and survival, with specific regulatory functions in gastrointestinal mucosal repair, hepatocyte function, and overall metabolic homeostasis. Dysregulation of IGF-1 signaling has been implicated in various conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD), and its balance is crucial for tissue maintenance. Despite its known pleiotropic effects and importance for systemic health, a systematic, large-scale epidemiological analysis comprehensively linking circulating IGF-1 levels to a broad spectrum of digestive diseases has been notably absent, leaving a significant gap in understanding its full impact on gastrointestinal health.
Study Design
Researchers conducted a prospective analysis of 461,401 UK Biobank participants, aged 40-69 years, with baseline IGF-1 measurements. Participants were followed up to August 2024 (median: 66-184 months). IGF-1 levels were stratified into quartiles (Q1 ≤ 17.525 nmol/L, Q2 17.526-21.253 nmol/L, Q3 21.254-24.825 nmol/L, Q4 ≥ 24.826 nmol/L). Cox proportional hazards regression and restricted cubic spline (RCS) analyses were employed to assess associations between IGF-1 levels and 27 ICD-10-classified digestive diseases.
Results
Cox proportional hazards regression models confirmed inverse associations between IGF-1 levels and 17 distinct digestive diseases. Further RCS analysis uncovered critical non-linear relationships, highlighting that both low and high IGF-1 levels can be detrimental to gastrointestinal health. Specifically, IGF-1 deficiency was significantly associated with an increased risk of 19 different digestive diseases. Conversely, excessively high IGF-1 levels were linked to an elevated risk for specific conditions.
> 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 also exhibited a non-linear positive correlation with IGF-1 levels, suggesting a complex dose-response relationship where risk increases with higher IGF-1 but not necessarily linearly.
Key Findings
- IGF-1 deficiency increased risk for 19 different digestive diseases.
- Excessively high IGF-1 levels raised risk for ventral hernia, paralytic ileus, diverticular disease, and haemorrhoids.
- Inguinal hernia showed a non-linear positive correlation with IGF-1 levels.
Cox regressionfound inverse associations between IGF-1 levels and 17 digestive diseases.
Why It Matters
This extensive prospective analysis provides unprecedented clarity on the complex, non-linear relationship between circulating IGF-1 levels and a wide array of digestive diseases. The key takeaway for clinicians and biohackers is the critical importance of maintaining optimal IGF-1 levels, as both deficiency and excess are associated with increased risk for distinct gastrointestinal pathologies. This moves beyond a simplistic 'more is better' paradigm for IGF-1, suggesting that personalized monitoring and modulation of IGF-1 might be beneficial. For example, individuals with low IGF-1 may need interventions to support its production, while those with high levels might need to address underlying factors contributing to that elevation, especially if they present with conditions like hernias or diverticular disease. This research lays a foundation for future studies to explore the mechanisms behind these non-linear associations and potentially develop targeted preventative or therapeutic strategies for digestive health.
igf-1
digestive-diseases
gastrointestinal-health
cohort-study
epidemiology
uk-biobank