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Abstract：
Multiple observational studies have demonstrated an association between type 2 diabetes mellitus (T2DM) and chronic liver diseases (CLDs). However, the causality of T2DM on CLDs remained unknown in various ethnic groups.
We obtained instrumental variables for T2DM and conducted a two-sample mendelian randomization (MR) study to examine the causal effect on nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), viral hepatitis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection risk in Europeans and East Asians. The primary analysis utilized the inverse variance weighting (IVW) technique to evaluate the causal relationship between T2DM and CLDs. In addition, we conducted a series of rigorous analyses to bolster the reliability of our MR results.
In Europeans, we found that genetic liability to T2DM has been linked with increased risk of NAFLD (IVW : OR =1.3654, 95% confidence interval [CI], 1.2250-1.5219, p=1.85e-8), viral hepatitis (IVW : OR =1.1173, 95%CI, 1.0271-1.2154, p=0.0098), and a suggestive positive association between T2DM and HCC (IVW : OR=1.2671, 95%CI, 1.0471-1.5333, p=0.0150), HBV (IVW : OR=1.1908, 95% CI, 1.0368-1.3677, p=0.0134). No causal association between T2DM and HCV was discovered. Among East Asians, however, there was a significant inverse association between T2DM and the proxies of NAFLD (ALT: IVW OR=0.9752, 95%CI 0.9597-0.9909, p=0.0021; AST: IVW OR=0.9673, 95%CI, 0.9528-0.9821, p=1.67e-5), and HCV (IVW: OR=0.9289, 95%CI, 0.8852-0.9747, p=0.0027). Notably, no causal association was found between T2DM and HCC, viral hepatitis, or HBV.
Our MR analysis revealed varying causal associations between T2DM and CLDs in East Asians and Europeans. Further research is required to investigate the potential mechanisms in various ethnic groups, which could yield new insights into early screening and prevention strategies for CLDs in T2DM patients.
We obtained instrumental variables for T2DM and conducted a two-sample mendelian randomization (MR) study to examine the causal effect on nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), viral hepatitis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection risk in Europeans and East Asians. The primary analysis utilized the inverse variance weighting (IVW) technique to evaluate the causal relationship between T2DM and CLDs. In addition, we conducted a series of rigorous analyses to bolster the reliability of our MR results.
In Europeans, we found that genetic liability to T2DM has been linked with increased risk of NAFLD (IVW : OR =1.3654, 95% confidence interval [CI], 1.2250-1.5219, p=1.85e-8), viral hepatitis (IVW : OR =1.1173, 95%CI, 1.0271-1.2154, p=0.0098), and a suggestive positive association between T2DM and HCC (IVW : OR=1.2671, 95%CI, 1.0471-1.5333, p=0.0150), HBV (IVW : OR=1.1908, 95% CI, 1.0368-1.3677, p=0.0134). No causal association between T2DM and HCV was discovered. Among East Asians, however, there was a significant inverse association between T2DM and the proxies of NAFLD (ALT: IVW OR=0.9752, 95%CI 0.9597-0.9909, p=0.0021; AST: IVW OR=0.9673, 95%CI, 0.9528-0.9821, p=1.67e-5), and HCV (IVW: OR=0.9289, 95%CI, 0.8852-0.9747, p=0.0027). Notably, no causal association was found between T2DM and HCC, viral hepatitis, or HBV.
Our MR analysis revealed varying causal associations between T2DM and CLDs in East Asians and Europeans. Further research is required to investigate the potential mechanisms in various ethnic groups, which could yield new insights into early screening and prevention strategies for CLDs in T2DM patients.
摘要：
■多项观察性研究表明2型糖尿病（T2DM）与慢性肝病（CLD）之间存在关联。然而,T2DM对CLDs的因果关系在不同种族中仍然未知.
■我们获得了T2DM的工具变量，并进行了双样本孟德尔随机化（MR）研究，以检查非酒精性脂肪肝（NAFLD）的因果关系。肝细胞癌（HCC），病毒性肝炎,乙型肝炎病毒（HBV）感染，欧洲人和东亚人的丙型肝炎病毒（HCV）感染风险。主要分析使用逆方差加权（IVW）技术来评估T2DM和CLD之间的因果关系。此外,我们进行了一系列严格的分析,以增强MR结果的可靠性.
■在欧洲人中，我们发现，T2DM的遗传倾向与NAFLD的风险增加有关（IVW：OR=1.3654，95％置信区间[CI]，1.2250-1.5219，p=1.85e-8)，病毒性肝炎（IVW：OR=1.1173，95CI，1.0271-1.2154，p=0.0098），T2DM和HCC之间存在暗示性正相关（IVW：OR=1.2671，95CI，1.0471-1.5333，p=0.0150），HBV（IVW：OR=1.1908，95%CI，1.0368-1.3677，p=0.0134）。未发现T2DM和HCV之间的因果关系。在东亚人中，然而,T2DM与NAFLD的代理之间存在显着负相关（ALT：IVWOR=0.9752，95CI0.9597-0.9909，p=0.0021；AST：IVWOR=0.9673，95CI，0.9528-0.9821，p=1.67e-5），和HCV（IVW：OR=0.9289，95CI，0.8852-0.9747，p=0.0027）。值得注意的是,T2DM和HCC之间没有因果关系，病毒性肝炎,或HBV。
■我们的MR分析揭示了东亚人和欧洲人的T2DM和CLDs之间不同的因果关系。需要进一步研究，以调查各个种族群体的潜在机制，这可能会对T2DM患者CLDs的早期筛查和预防策略产生新的见解。
■我们获得了T2DM的工具变量，并进行了双样本孟德尔随机化（MR）研究，以检查非酒精性脂肪肝（NAFLD）的因果关系。肝细胞癌（HCC），病毒性肝炎,乙型肝炎病毒（HBV）感染，欧洲人和东亚人的丙型肝炎病毒（HCV）感染风险。主要分析使用逆方差加权（IVW）技术来评估T2DM和CLD之间的因果关系。此外,我们进行了一系列严格的分析,以增强MR结果的可靠性.
■在欧洲人中，我们发现，T2DM的遗传倾向与NAFLD的风险增加有关（IVW：OR=1.3654，95％置信区间[CI]，1.2250-1.5219，p=1.85e-8)，病毒性肝炎（IVW：OR=1.1173，95CI，1.0271-1.2154，p=0.0098），T2DM和HCC之间存在暗示性正相关（IVW：OR=1.2671，95CI，1.0471-1.5333，p=0.0150），HBV（IVW：OR=1.1908，95%CI，1.0368-1.3677，p=0.0134）。未发现T2DM和HCV之间的因果关系。在东亚人中，然而,T2DM与NAFLD的代理之间存在显着负相关（ALT：IVWOR=0.9752，95CI0.9597-0.9909，p=0.0021；AST：IVWOR=0.9673，95CI，0.9528-0.9821，p=1.67e-5），和HCV（IVW：OR=0.9289，95CI，0.8852-0.9747，p=0.0027）。值得注意的是,T2DM和HCC之间没有因果关系，病毒性肝炎,或HBV。
■我们的MR分析揭示了东亚人和欧洲人的T2DM和CLDs之间不同的因果关系。需要进一步研究，以调查各个种族群体的潜在机制，这可能会对T2DM患者CLDs的早期筛查和预防策略产生新的见解。
