Abstract #1405175: Temporal Association Between Nonalcoholic Fatty Liver Disease and Type 2 Diabetes: Observational and Mendelian Randomization Study

Abstract

Nonalcoholic fatty liver disease and diabetes are both chronic multi-system disease and their prevalence are emerging every year, causing considerable clinical and health burden worldwide. Previous epidemiological studies have found a bidirectional relationship between them but the actual causal effect remained unknown. We aim to verify this bidirectional association and find out the exact causal relationship between these two diseases. The study consisted of two datasets. The SPECT-China dataset included 2099 participants who attended SPECT-China 2014 and SPECT-China2 2019 simultaneously, and the UK Biobank dataset included 502414 participants aged 37-73 years across the UK. SNPs were extracted from IEU OPEN GWAS PROJECT. Logistic regression model and cox regression model were used to analyze the association between NAFLD and T2DM. Bidirectional mendelian randomization analysis were conducted to investigate the causal effects. During the follow-up, 129 cases of diabetes and 263 cases of NAFLD were observed in the SPECT-China dataset, and 30274 cases of diabetes and 4896 cases of NAFLD happened in the UK Biobank dataset. Baseline NAFLD is associated with an increased risk of incident T2DM in both datasets while baseline diabetes is only associated with incident NAFLD in the UK Biobank dataset. Bidirectional MR analysis found a causal relationship from NAFLD to T2DM. (OR: 1.05, 95%CI :1.03-1.07, P< 0.001) We found a potentially causal NAFLD→T2DM relationship, therefore public awareness should be raised in maintaining an optimal glycemic profile, especially in those with NAFLD.