Han Dongxu, Liu Jingnan, Wang Yu, Wang Hongxia, Yuan Lingdan, Jin Wei, Song Lige
Department of Endocrinology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, China.
Front Endocrinol (Lausanne). 2025 Feb 26;16:1490214. doi: 10.3389/fendo.2025.1490214. eCollection 2025.
A20, also known as TNF-α-induced protein 3 (TNFAIP3), is a crucial negative regulator of inflammation and immune responses. Emerging evidence suggests that A20 is involved in the regulation of glucose metabolism and plays a significant role in bone metabolic diseases by inhibiting nuclear factor (NF)-κB activation. However, the potential relationship between serum A20 level and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM) has not been explored. This study aims to investigate the association between serum A20 level with BMD and bone turnover markers (BTMs) in patients with T2DM.
A total of 189 patients with T2DM and 183 non-diabetic individuals were included in the study based on the inclusion and exclusion criteria. Participants were categorized into normal BMD and low BMD groups. Baseline clinical histories were collected through face-to-face questionnaires. Participants underwent measurements of blood biochemistry and anthropometric, hand grip strength records and short physical performance battery (SPPB) assessment. Serum A20 level was quantified by enzyme-linked immunosorbent assay kit. Areal BMD was measured using dual-energy x-ray absorptiometry (DXA). A T-score of less than -1.0 at the lumbar spine 1-4, femoral neck and/or total hip was classified as low BMD.
Serum A20 level was lower in patients with T2DM compared to controls [41.30 (29.91, 61.87) vs 76.01 (54.90, 109.64) pg/mL, P<0.001]. Bivariate correlation analysis revealed that A20 level was not associated with SPPB but negatively correlated with waist-to-hip ratio (WHR). Pearson correlation analysis showed A20 level was positively correlated with lumbar spine 1-4 BMD in male diabetic patients (r=0.253, P=0.032). Multivariate regression analysis showed a positive association between serum A20 level and lumbar spine 1-4 BMD (Beta=0.047; 95% CI: 0.007-0.086; P=0.024) after multivariate adjustment. Logistic regression analysis showed that lower serum A20 level predicted low BMD in male patients with T2DM (OR: 0.22; 95% CI: 0.09-0.59; P=0.002).
Type 2 diabetic patients exhibited lower serum A20 level compared to non-diabetic individuals. In male patients with T2DM, serum A20 level showed a significant positive correlation with lumbar spine 1-4 BMD and could serve as an independent negative predictor for low BMD.
A20，也称为肿瘤坏死因子-α诱导蛋白3（TNFAIP3），是炎症和免疫反应的关键负调节因子。新出现的证据表明，A20参与葡萄糖代谢的调节，并通过抑制核因子（NF）-κB激活在骨代谢疾病中发挥重要作用。然而，2型糖尿病（T2DM）患者血清A20水平与骨密度（BMD）之间的潜在关系尚未得到探索。本研究旨在探讨T2DM患者血清A20水平与BMD及骨转换标志物（BTMs）之间的关联。
根据纳入和排除标准，共有189例T2DM患者和183例非糖尿病个体纳入本研究。参与者被分为正常BMD组和低BMD组。通过面对面问卷调查收集基线临床病史。参与者接受血液生化、人体测量、握力记录和短身体性能测试（SPPB）评估。血清A20水平采用酶联免疫吸附测定试剂盒进行定量。使用双能X线吸收法（DXA）测量面积BMD。腰椎1-4、股骨颈和/或全髋部T值小于-1.0被分类为低BMD。
与对照组相比，T2DM患者血清A20水平较低[41.30（29.91，61.87）对76.01（54.90，109.64）pg/mL，P<0.001]。双变量相关性分析显示，A20水平与SPPB无关，但与腰臀比（WHR）呈负相关。Pearson相关性分析显示，男性糖尿病患者A20水平与腰椎1-4 BMD呈正相关（r=0.253，P=0.032）。多变量回归分析显示，多变量调整后，血清A20水平与腰椎1-4 BMD呈正相关（β=0.047；95%CI：0.007-0.086；P=0.024）。Logistic回归分析显示，较低的血清A20水平可预测男性T2DM患者的低BMD（OR：0.22；95%CI：0.09-0.59；P=0.002）。
与非糖尿病个体相比，2型糖尿病患者血清A20水平较低。在男性T2DM患者中，血清A20水平与腰椎1-4 BMD呈显著正相关，可作为低BMD的独立负性预测指标。
