Data Sheet 1_Association between steatotic liver disease and microvascular complications in individuals with type 2 diabetes: a cohort study in the UK Biobank.docx

BackgroundCross-sectional studies have revealed that steatotic liver disease (SLD) is associated with prevalent diabetic microvascular complications, but longitudinal evidence in large samples is insufficient. We aimed to prospectively investigate the association between SLDs and the risk of microvascular complications in patients with type 2 diabetes (T2D), and to explore whether glycemic control played a mediating role in this association.
MethodsThe population-based cohort, which was based on the UK Biobank study, included 25,630 T2D patients at baseline. SLD was defined as a fatty liver index ≥ 60. A glycated hemoglobin level ≥ 7% (53 mmol/mol) was considered poor glycemic control. The primary outcome was total incident diabetic microvascular complications, defined as the first occurrence of diabetic nephropathy, diabetic neuropathy, and/or diabetic retinopathy. The cox proportional hazard regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for diabetic microvascular complications. Mediation analysis was applied to explore whether the association between SLDs and diabetic microvascular complications was mediated by glycemic control.
ResultsThe mean age of the study participants was 59.6 years, and 58.1% of them were males. During a median follow-up period of 12.1 years, 5,171 participants were diagnosed with microvascular complications. Compared with non-SLD participants, SLD participants had a HR of 1.15 (95% CI: 1.04, 1.27) for total microvascular complications, a HR of 1.20 (95% CI: 1.06, 1.35) for diabetic nephropathy, a HR of 1.05 (95% CI: 0.91, 1.21) for diabetic retinopathy, and a HR of 1.46 (95% CI: 1.15, 1.86) for diabetic neuropathy. The results of the mediation analysis revealed that the mediating proportion of glycemic control in the association between the SLD group and total diabetic microvascular complications was 22.5% (95% CI: 10.4%, 91.0%).
ConclusionsSLD was associated with an increased risk of microvascular complications, especially diabetic nephropathy and diabetic neuropathy, in T2D patients. Glycemic control partially mediated the association between SLDs and diabetic microvascular complications.

### 背景
既往横断面研究已表明，脂肪性肝病（steatotic liver disease, SLD）与已确诊的糖尿病微血管并发症存在关联，但大样本的纵向研究证据仍较为匮乏。本研究旨在前瞻性探究2型糖尿病（type 2 diabetes, T2D）患者的脂肪性肝病与微血管并发症发病风险之间的关联，并探讨血糖控制是否在该关联中发挥中介作用。

### 方法
本研究基于英国生物银行（UK Biobank）构建人群队列，基线共纳入25630名2型糖尿病患者。本研究将脂肪肝指数≥60定义为脂肪性肝病；将糖化血红蛋白≥7%（53 mmol/mol）判定为血糖控制不佳。主要结局为新发糖尿病微血管并发症总和，定义为糖尿病肾病、糖尿病神经病变及/或糖尿病视网膜病变的首次发生。本研究采用Cox比例风险回归模型计算糖尿病微血管并发症的风险比（hazard ratios, HRs）及95%置信区间（95% confidence intervals, CIs），并通过中介分析探究血糖控制是否介导脂肪性肝病与糖尿病微血管并发症之间的关联。

### 结果
本研究纳入的参与者平均年龄为59.6岁，其中男性占比58.1%。在中位随访12.1年期间，共有5171名参与者被诊断为微血管并发症。与非脂肪性肝病参与者相比，脂肪性肝病参与者的总微血管并发症风险比为1.15（95% CI: 1.04, 1.27），糖尿病肾病风险比为1.20（95% CI: 1.06, 1.35），糖尿病视网膜病变风险比为1.05（95% CI: 0.91, 1.21），糖尿病神经病变风险比为1.46（95% CI: 1.15, 1.86）。中介分析结果显示，血糖控制在脂肪性肝病组与总糖尿病微血管并发症关联中的中介占比为22.5%（95% CI: 10.4%, 91.0%）。

### 结论
在2型糖尿病患者中，脂肪性肝病与微血管并发症的发病风险升高相关，尤其是糖尿病肾病与糖尿病神经病变。血糖控制在脂肪性肝病与糖尿病微血管并发症的关联中发挥部分中介作用。