Liu Longfu, You Qiqi, Yu Wenxiang, Lett Aaron M, Wu Yucen, Zeng Jingjing, Fan Menglin, Chen Bo, Fu Wan, Xu Shaoyong
Department of Endocrinology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.
Center for Clinical Evidence-Based and Translational Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.
Front Endocrinol (Lausanne). 2025 May 28;16:1554798. doi: 10.3389/fendo.2025.1554798. eCollection 2025.
Cross-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.
The 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.
The 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%).
SLD 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.
横断面研究表明，脂肪性肝病（SLD）与糖尿病微血管并发症的患病率相关，但大样本的纵向证据不足。我们旨在前瞻性研究SLD与2型糖尿病（T2D）患者微血管并发症风险之间的关联，并探讨血糖控制是否在这种关联中起中介作用。
基于英国生物银行研究的人群队列在基线时纳入了25,630例T2D患者。SLD定义为脂肪肝指数≥60。糖化血红蛋白水平≥7%（53 mmol/mol）被认为血糖控制不佳。主要结局是糖尿病微血管并发症的总发生率，定义为首次出现糖尿病肾病、糖尿病神经病变和/或糖尿病视网膜病变。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（HR）和95%置信区间（CI）。应用中介分析来探讨SLD与糖尿病微血管并发症之间的关联是否由血糖控制介导。
研究参与者的平均年龄为59.6岁，其中58.1%为男性。在中位随访期12.1年期间，5171名参与者被诊断出患有微血管并发症。与非SLD参与者相比，SLD参与者发生总微血管并发症的HR为1.15（95%CI：1.04，1.27），糖尿病肾病的HR为1.20（95%CI：1.06，1.35），糖尿病视网膜病变的HR为1.05（95%CI：0.91，1.21），糖尿病神经病变的HR为1.46（95%CI：1.15，1.86）。中介分析结果显示，血糖控制在SLD组与糖尿病微血管并发症总发生率之间的关联中的中介比例为22.5%（95%CI：10.4%，91.0%）。
SLD与T2D患者微血管并发症风险增加相关，尤其是糖尿病肾病和糖尿病神经病变。血糖控制部分介导了SLD与糖尿病微血管并发症之间的关联。
