中国全科医学2018，Vol.21Issue(12)：1419-1427,9.DOI:10.3969/j.issn.1007-9572.2018.00.081
应激相关microRNA在2型糖尿病及糖尿病前期患者中的表达规律及意义研究
Expression and Significance of Stress-Related microRNA in Patients with Type 2 Diabetes and Pre-diabetes
摘要
Abstract
Objective To explore the expression pattern and significance of stress-related microRNA (miRNAs) in patients with type 2 diabetes (T2DM) and pre-diabetes.Methods From the occupational populations undergoing physical examination at Xuanwu Hospital,Capital Medical University during May to September 2016,we recruited 70 with new-onset T2DM (case group),42 with impaired fasting glucose (IFG) (pre-diabetes group),and also enrolled sex-matched and age-matched (within ±3 years range) 53 controls with normal fasting plasma glucose,glycosylated hemoglobin and blood lipids based on group-matching design.We collected their baseline characteristics and detected the level of stress-related hormones.Among the T2DM patients' significantly different expressed plasma stress-related miRNAs identified by miRNAs microarray analysis,we screened 7 plasma stress-related miRNAs (let-7b,let-7i,miR-142,miR-144,miR-155 and miR-29a) by bioinformatics analysis.Furthermore,we used qRT-PCR to detect the expression levels of these 7 miRNAs in plasma.Results Compared with the controls,both pre-diabetic and T2DM patients showed higher average levels of corticotropin-releasing hormone (CRH) and cortisol (Cor) (P<0.05),moreover,T2DM patients also presented higher average levels of interleukin-6 (IL-6),epinephrine (E),and norepinephrine (NE) (P<0.05).The average Cor level was higher in the T2DM cases than that of the pre-diabetic cases (P<0.05).Compared with the controls,the average plasma let-7b,miR-144 and miR-29a levels were significantly higher but average miR-142 level was lower in pre-diabetic and T2DM patients (P<0.05).The average plasma let-7b level was higher in T2DM patients than that in pre-diabetic patients (P<0.05). Among all the participants,plasma CRH was positively correlated with let-7b and miR-144 (P<0.05);plasma IL-6,E and NE were positively correlated with let-7b (P<0.05);plasma Cor was positively correlated with let-7b,miR-144 and miR-29 (P<0.05).Moreover,all of stress-related hormones in our study were negatively correlated with miR-142.In case group,plasm CRH,E and NE showed significant positive correlation with let-7b (P<0.05);IL-6 was negatively correlated with miR-142 (P<0.05);and Cor was positively correlated with miR-144 and miR-29a (P<0.05).Multivariate Logistic regression analysis revealed that up-regulated let-7b conferred an increased risk of future T2DM while elevated miR-142 was contributive to reducing the risk of T2DM (P<0.05);up-regulated miR-144 and miR-29a were risk factors for IFG (P<0.05).The miRNAs panel of let-7b,miR-142 and miR-144 distinguished T2DM patients from the healthy controls showed an area under the curve (AUC) of 0.880 [95%CI (0.820,0.941)],the cut-off point was 0.626 with corresponding sensitivity and specificity of 78.6% and 84.9%,respectively.The cross-validation showed that the average accuracy was 0.853.The federal panel of SBP,DBP,BMI, WHR,TC,TG,HDL-C,LDL-C,let-7b,miR-142 and miR-144 presented an AUC of 0.937 [95%CI (0.897,0.977)], the cut-off point was 0.680 with sensitivity and specificity of 82.9% and 94.3%,respectively.The cross-validation showed that the average accuracy was 0.902.Conclusion Compared with the controls,plasma let-7b and miR-144 levels were up-regulated but miR-142 level was down-regulated in pre-diabetic and T2DM patients,suggesting that let-7b,miR-142 and miR-144 may involve in the pathogenesis of pre-diabetes as well as T2DM by adjusting the stress reaction.关键词
糖尿病,2型/糖尿病前期/微RNAs/应激Key words
Diabetes mellitus/type 2/Prediabetic state/MicroRNAs/Stress分类
医药卫生引用本文复制引用
梁英智,闫宇翔..应激相关microRNA在2型糖尿病及糖尿病前期患者中的表达规律及意义研究[J].中国全科医学,2018,21(12):1419-1427,9.基金项目
国家自然科学基金资助项目(81573214) （81573214）
