Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study
BackgroundNAFLD (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 o...
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2024.1315046/full |
| _version_ | 1797213527597907968 |
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| author | Lin Tuo Li-ting Yan Yi Liu Xing-xiang Yang |
| author_facet | Lin Tuo Li-ting Yan Yi Liu Xing-xiang Yang |
| author_sort | Lin Tuo |
| collection | DOAJ |
| description | BackgroundNAFLD (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.MethodsWe 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.ResultsWe 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.ConclusionOur 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. |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-24T10:59:42Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-63c78fce141541bfacf41909add78ec02024-04-12T04:18:22ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-04-011510.3389/fendo.2024.13150461315046Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization studyLin TuoLi-ting YanYi LiuXing-xiang YangBackgroundNAFLD (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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fendo.2024.1315046/fulltwo-sample Mendelian randomizationtype 1 diabetes mellitusnon-alcoholic fatty liver diseasemetabolic syndromecausality |
| spellingShingle | Lin Tuo Li-ting Yan Yi Liu Xing-xiang Yang Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study Frontiers in Endocrinology two-sample Mendelian randomization type 1 diabetes mellitus non-alcoholic fatty liver disease metabolic syndrome causality |
| title | Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study |
| title_full | Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study |
| title_fullStr | Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study |
| title_full_unstemmed | Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study |
| title_short | Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study |
| title_sort | type 1 diabetes mellitus and non alcoholic fatty liver disease a two sample mendelian randomization study |
| topic | two-sample Mendelian randomization type 1 diabetes mellitus non-alcoholic fatty liver disease metabolic syndrome causality |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1315046/full |
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