AUTHOR=Tuo Lin , Yan Li-ting , Liu Yi , Yang Xing-xiang 

TITLE=Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study

JOURNAL=Frontiers in Endocrinology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1315046

DOI=10.3389/fendo.2024.1315046

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>NAFLD (Nonalcoholic fatty liver disease) is becoming an increasingly common cause of chronic liver disease. Metabolic dysfunction, overweight/obesity, and diabetes are thought to be closely associated with increased NAFLD risk. However, few studies have focused on the mechanisms of NAFLD occurrence in T1DM.</p></sec><sec><title>Methods</title><p>We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal association between T1DM and NAFLD with/without complications, such as coma, renal complications, ketoacidosis, neurological complications, and ophthalmic complications. Multiple Mendelian randomization methods, such as the inverse variance weighted (IVW) method, weighted median method, and MR-Egger test were performed to evaluate the causal association of T1DM and NAFLD using genome-wide association study summary data from different consortia, such as Finngen and UK biobank.</p></sec><sec><title>Results</title><p>We selected 37 SNPs strongly associated with NAFLD/LFC (at a significance level of <italic>p</italic> &lt; 5 × 10−8) as instrumental variables from the Finnish database based on the T1DM phenotype (8,967 cases and 308,373 controls). We also selected 14/16 SNPs based on with or without complications. The results suggest that the genetic susceptibility of T1DM does not increase the risk of NAFLD (OR=1.005 [0.99, 1.02], IVW p=0.516, MR Egger <italic>p</italic>=0.344, Weighted median <italic>p</italic>=0.959, Weighted mode <italic>p</italic>=0.791), regardless of whether complications are present. A slight causal effect of T1DM without complications on LFC was observed (OR=1.025 [1.00, 1.03], MR Egger <italic>p</italic>=0.045). However, none of the causal relationships were significant in the IVW (<italic>p</italic>=0.317), Weighted median (<italic>p</italic>=0.076), and Weighted mode (<italic>p</italic>=0.163) methods.</p></sec><sec><title>Conclusion</title><p>Our study did not find conclusive evidence for a causal association between T1DM and NAFLD, although clinical observations indicate increasing abnormal transaminase prevalence and NAFLD progression in T1DM patients.</p></sec>