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

Front Endocrinol (Lausanne). 2024 Apr 12:15:1315046. doi: 10.3389/fendo.2024.1315046. eCollection 2024.

Abstract

Background: 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.

Methods: 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.

Results: We selected 37 SNPs strongly associated with NAFLD/LFC (at a significance level of p < 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 p=0.344, Weighted median p=0.959, Weighted mode p=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 p=0.045). However, none of the causal relationships were significant in the IVW (p=0.317), Weighted median (p=0.076), and Weighted mode (p=0.163) methods.

Conclusion: 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.

Keywords: causality; metabolic syndrome; non-alcoholic fatty liver disease; two-sample Mendelian randomization; type 1 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / epidemiology
  • Diabetes Mellitus, Type 1* / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Mendelian Randomization Analysis*
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / epidemiology
  • Non-alcoholic Fatty Liver Disease* / genetics
  • Polymorphism, Single Nucleotide*

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Young Talent Fund of Sichuan Provincial People’s Hospital (No. 2020QN03), and the Scientific Research Fund of Chengdu Science and Technology Bureau (2020-YF05-00053-SN).