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 peptide β degradation 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.
Expression of serum miR-9-5p and NFAT5 in patients with type 2 diabetes mellitus and osteoporosis and its relationship with fractures
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 RT-PCR.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 peptide β degradation 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,and β-CTX,and negatively correlated with PINP(all P<0.05).Conversely,serum NFAT5 levels were negatively correlated with FPG,HOMA-IR,and β-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.
type 2 diabetes mellitusosteoporosismicroRNA-9-5pnuclear factor of activated T-cells 5fractures
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