2型糖尿病合并骨质疏松患者血清miR-9-5p和NFAT5的表达及其与骨折的关系

Expression of serum miR-9-5p and NFAT5 in patients with type 2 diabetes mellitus and osteoporosis and its relationship with fractures

目的:2型糖尿病(type 2 diabetes mellitus,T2DM)是一种多病因代谢性疾病,骨质疏松(osteoporosis,OP)和骨折是其常见并发症。本研究旨在探讨T2DM合并OP患者血清中微RNA(microRNA,miR)-9-5p和核转录因子5(nuclear factor of activated T-cells 5,NFAT5)的表达水平,以及其与骨折的关系。方法:收集郑州市第七人民医院就诊的T2DM合并OP患者184例(OP组),另纳入同时间段单纯T2DM患者184例(T2DM组)。实时聚合酶链反应检测血清miR-9-5p、NFAT5表达水平。随访2年,根据新发骨折情况,将T2DM合并OP患者分为骨折组(43例)与无骨折组(141例)。Pearson法分析血清miR-9-5p、NFAT5分别与空腹血糖(fasting plasma glucose,FPG)、I型前胶原N末端前肽(procollagen I N-terminal propeptide,PINP)、空腹胰岛素(fasting insulin,FINS)、胰岛素抵抗指数(insulin resistance index,HOMA-IR)、骨密度T值、I型胶原羧基端β降解产物(type I collagen hydroxy terminal peptideβdegradation products,β-CTX)相关性,以及miR-9-5p与NFAT5的相关性;采用受试者操作特征(receiver operator characteristic,ROC)曲线评估血清miR-9-5p、NFAT5对T2DM合并OP患者骨折的预测价值,多因素logistic回归分析T2DM合并OP患者骨折的影响因素。结果:OP组血清miR-9-5p水平高于T2DM组,NFAT5水平低于T2DM组(均P<0.05)。与无骨折组相比,骨折组患者糖尿病病程、FPG、HOMA-IR、β-CTX、miR-9-5p水平均升高,而PINP、NFAT5水平均降低(均P<0.05)。骨折患者血清miR-9-5p与NFAT5水平呈负相关(r=−0.716,P<0.05);miR-9-5p水平与FPG、HOMA-IR、β-CTX均呈正相关,与PINP呈负相关(均P<0.05),而血清NFAT5水平与FPG、HOMA-IR、β-CTX均呈负相关,与PINP呈正相关(均P<0.05)。血清miR-9-5p、NFAT5单一预测T2DM合并OP患者骨折风险的曲线下面积(area under curve,AUC)分别为0.878和0.868,联合预测的AUC为0.933。β-CTX、miR-9-5p为T2DM合并OP患者骨折的危险因素,PINP、NFAT5为T2DM合并OP患者骨折的保护因素(均P<0.05)。结论:T2DM合并OP患者血清miR-9-5p表达水平升高,NFAT5表达水平降低,两者与骨折发生均有一定关系,miR-9-5p联合NFAT5对骨折预测价值更高。

Objective:Type 2 diabetes mellitus(T2DM)is a multi-factorial metabolic disease,with osteoporosis(OP)and fractures being common complications.This study aims to investigate the expression levels of serum microRNA(miR)-9-5p and nuclear factor of activated T-cells 5(NFAT5)in patients with T2DM combined with OP,and their relationship with fractures.Methods:A total of 184 patients with T2DM combined with OP(OP group)and 184 patients with T2DM alone(T2DM group)were recruited from the 7th People’s Hospital of Zhengzhou.The expression levels of serum miR-9-5p and NFAT5 were detected by RTPCR.Over a follow-up period of 2 years,patients with T2DM combined with OP were divided into a fracture group(43 cases)and a non-fracture group(141 cases)based on new fracture occurrences.Pearson correlation analysis was used to examine the relationships between serum miR-9-5p,NFAT5,fasting plasma glucose(FPG),procollagen I N-terminal propeptide(PINP),fasting insulin(FINS),insulin resistance index(HOMA-IR),bone density T-score,and type I collagen hydroxy terminal peptideβdegradation products(β-CTX),as well as the correlation between miR-9-5p and NFAT5.The predictive value of serum miR-9-5p and NFAT5 for fractures in patients with T2DM combined with OP was assessed using receiver operator characteristic(ROC)curves.Multivariate logistic regression was used to analyze the factors influencing fractures in these patients.Results:The OP group had higher serum miR-9-5p levels and lower NFAT5 levels compared to the T2DM group(both P<0.05).Compared to the non-fracture group,the fracture group had longer diabetes duration,higher FPG,HOMA-IR,β-CTX,and miR-9-5p levels,and lower PINP and NFAT5 levels(all P<0.05).Serum miR-9-5p levels were negatively correlated NFAT5 levels(r=−0.716,P<0.05),and positively correlated with FPG,HOMA-IR,andβ-CTX,and negatively correlated with PINP(all P<0.05).Conversely,serum NFAT5 levels were negatively correlated with FPG,HOMA-IR,andβ-CTX,and positively correlated with PINP(all P<0.05).The area under the curve(AUC)for predicting fracture risk using serum miR-9-5p and NFAT5 alone were 0.878 and 0.868,respectively,while the combined prediction AUC was 0.933.β-CTX and miR-9-5p were identified as risk factors for fractures in patients with T2DM combined with OP,whereas PINP and NFAT5 were protective factors(all P<0.05).Conclusion:In patients with T2DM combined with OP,serum miR-9-5p expression levels are elevated,and NFAT5 expression levels are decreased.Both are associated with the occurrence of fractures,with the combination of miR-9-5p and NFAT5 having higher predictive value for fractures.