DataSheet_2_Type 1 diabetes and combined acute and chronic complications are associated with risk of progression of liver fibrosis: a Mendelian randomization study.pdf

BackgroundThere has been controversy and uncertainty regarding the causal relationship between type 1 diabetes, its consequences, liver fibrosis, and cirrhosis. In order to determine the causal relationship, we conducted a Mendelian randomization study (MR).
MethodsFor the first time, we subjected multiple diabetes data to analyze its relationship with the progression of liver fibrosis. Once the instrumental variables had been extracted, we assessed them employing Cochran’s Q multi-analysis, inverse variance weighted, MR-Egger, MR-PRESSO, weighted mode, and weighted median.
ResultsGenetically predicted type 1 diabetes (OR = 1.13, 95% CI: 1.04–1.23, **P = 3.42 × 10−3), type 1 diabetes without complications (OR = 1.12, 95% CI: 1.03–1.23, *P = 1.26 × 10−2), type 1 diabetes with coma (OR = 1.09, 95% CI: 1–1.18, *P = 4.74 × 10−2), type 1 diabetes with ketoacidosis (OR = 1.07, 95% CI: 1.01–1.13, *P = 1.3 × 10−2), type 1 diabetes with neurological complications (OR = 1.18, 95% CI: 1.11–1.26, ***P = 4.05 × 10−7), type 1 diabetes with ophthalmic complications (OR = 1.16, 95% CI: 1.05–1.28, **P = 3.06 × 10−3), type 1 diabetes with renal complications (OR = 1.07, 95% CI: 1–1.13, *P = 3.45 × 10−2), type 1 diabetes with other specified/multiple/unspecified complications (OR = 1.12, 95% CI: 1.02–1.23, *P = 1.41 × 10−2) were all associated with an increased risk of liver fibrosis progression.
ConclusionsAccording to our MR investigation, type 1 diabetes and both its acute and chronic implications may increase the likelihood that liver fibrosis could continue to develop. Additionally, type 1 diabetes with neurological and ocular problems is more likely to accelerate the development of liver fibrosis and inflammation, which offers new insights for genetic investigations.

研究背景：关于1型糖尿病、其并发症以及肝纤维化与肝硬化之间的因果关联，目前仍存在争议与不确定性。为明确该因果关系，本研究开展了孟德尔随机化（Mendelian randomization, MR）研究。
研究方法：本研究首次利用多组糖尿病数据，分析其与肝纤维化进展的关联。在提取工具变量后，我们采用Cochran Q检验、逆方差加权法、MR-Egger回归、MR-PRESSO检验、加权众数法以及加权中位数法对工具变量进行评估。
研究结果：遗传预测的1型糖尿病（比值比OR=1.13，95%置信区间CI:1.04~1.23，**P=3.42×10⁻³）、无并发症1型糖尿病（OR=1.12，95%CI:1.03~1.23，*P=1.26×10⁻²）、伴昏迷的1型糖尿病（OR=1.09，95%CI:1~1.18，*P=4.74×10⁻²）、伴酮症酸中毒的1型糖尿病（OR=1.07，95%CI:1.01~1.13，*P=1.3×10⁻²）、伴神经系统并发症的1型糖尿病（OR=1.18，95%CI:1.11~1.26，***P=4.05×10⁻⁷）、伴眼部并发症的1型糖尿病（OR=1.16，95%CI:1.05~1.28，**P=3.06×10⁻³）、伴肾脏并发症的1型糖尿病（OR=1.07，95%CI:1~1.13，*P=3.45×10⁻²）以及伴其他明确/多重/未明确并发症的1型糖尿病（OR=1.12，95%CI:1.02~1.23，*P=1.41×10⁻²）均与肝纤维化进展风险升高显著相关。
结论：基于本孟德尔随机化研究结果，1型糖尿病及其急慢性并发症均可能增加肝纤维化进展风险。此外，伴神经系统与眼部并发症的1型糖尿病更易加速肝纤维化及炎症进展，该发现为相关遗传学研究提供了新的视角。