Association of type 2 diabetes mellitus and other glycemic traits with the risk of NAFLD

Abstract Extensive observational evidence has proposed an association between Non-Alcoholic Fatty Liver Disease (NAFLD) and type 2 diabetes mellitus (T2DM). However, the causal relationship between these two diseases requires further investigation. Therefore, we assessed the potential causal relationship between NAFLD and T2DM and other glycaemic traits using two-sample Mendelian randomization (MR).We selected fasting insulin, T2DM, fasting glucose and Hemoglobin A1c(Hb1Ac) from meta-analyses of four genome-wide association studies (GWASs). GWAS data for NAFLD were obtained from the FinnGen consortium. MR analysis was accomplished using the inverse variance weighted (IVW) method, weighted median (WM) method, and MR-Egger regression analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy.The results showed that only fasting insulin and T2DM were significantly causally related to the risk of NAFLD when combined with the FinnGen consortium [fasting insulin, odds ratio (OR): 9.54; 95% confidence interval (CI) 2.66–34.16; P = 0.0005, T2DM :OR: 1.20; 95% CI 1.00- 1.45; P = 0.0497]. No significant association was observed between fasting glucose and HbA1c and the risk of NAFLD.This study supports the independent causal role of fasting insulin and T2DM in the pathogenesis of NAFLD, both of which are risk factors for the development of NAFLD.