Multiorgan Fibrosis and Risk of Type 2 Diabetes: Genetic and Observational Evidence Highlighting a Causal Role of Pancreatic Fibrosis.
Summary
A CT case-control study and Mendelian randomization converge to implicate pancreatic—rather than hepatic or myocardial—fibrosis in type 2 diabetes risk. The organ-specific association and genetic causality nominate pancreatic fibrosis as a mechanistically plausible, targetable pathway to preserve β-cell function.
Key Findings
- CT-based case-control: Greater pancreatic extracellular volume fraction associated with T2D (adjusted OR per 1-SD: 1.64; 95% CI 1.00–2.68), independent of confounders.
- Mendelian randomization: Genetically predicted pancreatic fibrosis increases T2D risk (OR per 1-SD: 1.43; 95% CI 1.09–1.89).
- No association for liver or myocardial fibrosis in either observational or genetic analyses, indicating organ specificity.
Clinical Implications
Supports evaluating pancreatic fibrosis as a biomarker for T2D risk and motivates trials of anti-fibrotic or fibrosis-modifying therapies aimed at β-cell preservation.
Why It Matters
Establishing pancreatic fibrosis as a likely causal risk factor for T2D reframes disease pathogenesis and opens avenues for imaging-based risk stratification and anti-fibrotic interventions.
Limitations
- Small CT case-control sample; extracellular volume fraction is an indirect fibrosis surrogate
- Potential MR pleiotropy and measurement heterogeneity across GWAS sources
Future Directions
Prospective imaging cohorts and interventional trials testing anti-fibrotic strategies to prevent T2D onset or preserve β-cell function.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- III - Imaging case-control combined with Mendelian randomization using large GWAS datasets
- Study Design
- OTHER