2型糖尿病合并骨质疏松患者血清miR-29c-3p、HDAC4的表达水平及其与骨折的关系-东南大学学报医学版

2型糖尿病合并骨质疏松患者血清miR-29c-3p、HDAC4的表达水平及其与骨折的关系

单位：河南中医药大学第五临床医学院/郑州人民医院内分泌代谢科, 河南郑州 450000

分类号：R587

出版年·卷·期（页码）：2026·45·第四期（647-653）

摘要：

目的:分析2型糖尿病(T2DM)合并骨质疏松症(OP)患者血清微小RNA-29c-3p(miR-29c-3p)、组蛋白去乙酰化酶4(HDAC4)表达对骨折的预测价值。方法:选取2022年8月至2024年9月本院收治的182例T2DM合并OP患者为合并OP组,同期182例未合并OP的T2DM患者为单纯T2DM组。根据1年随访期内是否发生骨折将T2DM合并OP患者分为无骨折亚组和骨折亚组。收集Ⅰ型胶原羧基端β降解产物(β-CTX)、25羟维生素D₃[25(OH)D₃]、Ⅰ型前胶原N末端前肽(PINP)等临床资料。采用实时荧光定量PCR法检测血清miR-29c-3p水平,ELISA法检测HDAC4水平。采用Pearson法分析相关性,Logistic回归分析影响因素,ROC曲线分析血清指标的预测价值,多因素非条件Logistic回归分析评估交互作用,决策曲线分析预测模型的临床适用性。结果:合并OP组血清miR-29c-3p表达低于单纯T2DM组,HDAC4质量浓度高于单纯T2DM组(P＜0.05)。骨折亚组β-CTX、HDAC4质量浓度高于无骨折亚组,25(OH)D₃、PINP、miR-29c-3p水平低于无骨折亚组(P＜0.05)。T2DM合并OP患者血清miR-29c-3p与25(OH)D₃、PINP正相关,与β-CTX负相关(P＜0.05);血清HDAC4与25(OH)D₃、PINP负相关,与β-CTX正相关(P＜0.05)。血清miR-29c-3p、HDAC4联合预测T2DM合并OP患者骨折的ROC曲线下面积高于单独预测(Z值分别为2.730、2.561,均P＜0.05)。血清miR-29c-3p、HDAC4在T2DM合并OP患者骨折风险中存在强交互效应,低miR-29c-3p和高HDAC4同时存在的效应是单独存在效应之和的1.812倍(P＜0.05)。联合预测模型的净收益高于miR-29c-3p、HDAC4单独净收益。结论:血清miR-29c-3p、HDAC4联合检测可作为临床预测T2DM合并OP患者骨折风险的可靠依据。

Objective: To analyze the predictive value of serum levels of microRNA-29c-3p(miR-29c-3p) and histone deacetylase 4(HDAC4) for fractures in type 2 diabetes mellitus(T2DM) patients with osteoporosis(OP). Methods: From August 2022 to September 2024, 182 T2DM patients with OP who visited our hospital were selected as combined OP group, and 182 T2DM patients without OP were as the simple T2DM group. The combined OP group was divided into a non-fracture subgroup and a fracture subgroup according to the occurrence of fracture during 1-year follow-up. Clinical data such as β-C-terminal telopeptide of type I collagen(β-CTX), 25-hydroxyvitamin D₃[25(OH)D₃], and procollagen type I N-terminal propeptide(PINP) were collected. Serum level of miR-29c-3p was detected by real-time fluorescence quantitative PCR, and HDAC4 was measured by ELISA. Pearson method was used to explore the correlation. Logistic regression was performed to analyze the influencing factors. Receiver operating characteristic(ROC) curve was used to explore the predictive value of serum indicators. Multivariate unconditional Logistic regression analysis was adopted to assess the interaction. Decision curve analysis evaluated the clinical applicability of the prediction model. Results: The serum miR-29c-3p level in the combined OP group was lower than that in the simple T2DM group, and HDAC4 level was higher than that in the simple T2DM group(P<0.05). Compared with the non-fracture subgroup, β-CTX and HDAC4 levels in the fracture subgroup were increased, while the 25(OH)D₃, PINP and miR-29c-3p levels were decreased(P<0.05). Serum miR-29c-3p in T2DM patients with OP was positively correlated with 25(OH)D3 and PINP, and negatively correlated with β-CTX(P<0.05). Serum HDAC4 was negatively correlated with 25(OH)D3 and PINP, and positively correlated with β-CTX(P<0.05). The combined prediction of serum miR-29c-3p and HDAC4 for fractures in T2DM patients with OP had a markedly larger AUC than the prediction using either biomarker alone(Z=2.730, 2.561, P<0.05). There was a strong interaction effect of serum miR-29c-3p and HDAC4 on fracture risk in T2DM patients with OP(P<0.05). The combined effect of low miR-29c-3p and high HDAC4 was 1.812 times the sum of the individual effects. The net benefit of the combined prediction model was higher than that of miR-29c-3p and HDAC4 alone. Conclusion: The combined detection of serum miR-29c-3p and HDAC4 can be used as a reliable serological biomarker panel to predict fracture risk in T2DM patients with OP.

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