Association between type 2 diabetes and autoimmune liver disease: An integrated analysis of Mendelian randomization and clinical samples

This study aims to determine the potential causal relationship between type 2 diabetes (T2D) and autoimmune liver disease (AILD) using Mendelian randomization (MR) combined with clinical case analysis. Summary statistics for T2D, autoimmune hepatitis, primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) were sourced from open genome-wide association study databases. The IVW method was used as the primary analysis. Additional sensitivity analysis was also performed to validate our results. Subsequently, clinical information on patients with AILD was collected retrospectively, while multiple potentially confounding independent effects were assessed using multivariate logistic regression analysis. The results of the forward MR analysis showed that genetically predicted T2D was associated with reduced risk of PSC (IVW: odds ratio [OR] = 0.85, 95% confidence interval [CI], 0.77–0.94, P = .001). Furthermore, the results of the reverse MR analysis revealed the genetically predicted PBC (OR = 1.96, 95% CI 1.31–3.40, P = .016) had a significant correlation with the higher risk of T2D (IVW: OR = 1.02, 95% CI, 1.00–1.04, P = .025). An analysis of the clinical sample revealed that the prevalence of T2D among patients with AILD was 27.6%. Notably, multifactorial logistic regression analysis indicated that immunoglobulin G and total bilirubin levels may serve as independent factors influencing the occurrence of T2D. Genetic evidence demonstrated that T2D reduced the risk of PSC, while PBC increased the risk of T2D. Clinical data further confirmed a high prevalence of T2D in patients with autoimmune liver disease, suggesting a bidirectional relationship that warrants further validation.