Pancreatic fibrosis has been proposed as a contributor to type 2 diabetes (T2D) by impairing islet function, but whether it plays a causal role remains unclear. We investigated this question using two complementary approaches. First, we performed a computed tomography–based retrospective case-control study (T2D case patients: n = 58; control participants: n = 58) assessing extracellular volume fraction as a marker of fibrosis in the pancreas, liver, and myocardium. Greater pancreatic fibrosis was associated with T2D (adjusted odds ratio [OR] per 1 [SD] increase: 1.64; 95% CI 1.00–2.68), independent of age, sex, BMI, liver fibrosis, and myocardial fibrosis. Second, we conducted a Mendelian randomization analysis using genome-wide association study (GWAS) data on multiorgan fibrosis derived from MRI in the UK Biobank (n = 43,881), along with T2D GWAS data from the Diabetes Genetics Replication and Meta-analysis (DIAGRAM) consortium (n = 242,283 T2D case patients and 1,569,734 control participants). Genetically predicted pancreatic fibrosis levels were associated with an increased T2D risk (OR per 1-SD increase: 1.43; 95% CI 1.09–1.89), whereas liver and myocardial fibrosis levels showed no associations. These findings support a potential causal and organ-specific role of pancreatic fibrosis in the pathogenesis of T2D, highlighting pancreatic fibrosis as a mechanistically plausible and potentially targetable target in diabetes prevention.
- Pancreatic, but not liver or myocardial, fibrosis is specifically and independently linked to type 2 diabetes.
- Mendelian randomization analysis reveals a causal role of pancreatic fibrosis in diabetes development.
- Pancreatic fibrosis might be a potential therapeutic target to preserve β-cell function and prevent diabetes.
Leave a Reply