2型糖尿病患者外周血circRNA LRP6表达水平与炎症因子和糖脂代谢的相关性

Correlation of peripheral blood circRNA LRP6 expression with inflammatory factors and glucose and lipid metabolism in patients with type 2 diabetes

目的分析2型糖尿病患者外周血环状RNA-低密度脂蛋白受体相关蛋白6(circRNA LRP6)表达水平,并探究其与患者炎症因子、糖脂代谢的相关性。方法以2021年1月-2022年4月青海大学附属医院收治的96例2型糖尿病患者为观察组,另选取同期健康志愿者88名为对照组。实时荧光定量PCR(qRT-PCR)法检测血清circRNA LRP6表达水平,酶联免疫吸附(ELISA)法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、超敏C反应蛋白(hs-CRP)、脂联素(APN)、网膜素-1(Omentin-1)水平;全自动生化分析仪检测总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)水平,全自动化学发光免疫分析仪检测空腹胰岛素(FINS)水平,全自动糖化血红蛋白分析仪测定糖化血红蛋白(HbA1c)水平。比较2组血清circRNA LRP6、TNF-α、IL-6、hs-CRP、APN、Omentin-1、TC、TG、HDL-C、LDL-C、FPG、FINS、HbA1c水平。采用Pearson相关性分析circRNA LRP6与炎症因子、糖脂代谢指标的相关性。采用多因素logistic回归分析2型糖尿病发生的影响因素。结果观察组血清circRNA LRP6、TNF-α、IL-6、hs-CRP、TC、TG、LDL-C、FPG、FINS、HbA1c水平[(1.55±0.32)、(12.55±1.72)pg/mL、(26.37±3.21)pg/mL、(13.15±2.98)mg/L、(5.84±0.61)mmol/L、(1.92±0.39)mmol/L、(3.85±0.46)mmol/L、(8.16±0.89)mmol/L、(13.25±1.96)μU/mL、(7.69±0.39)%]均明显高于对照组[(1.02±0.12)、(9.10±1.15)pg/mL、(16.28±2.56)pg/mL、(8.31±1.96)mg/L、(4.15±0.53)mmol/L、(1.26±0.22)mmol/L、(2.29±0.19)mmol/L、(4.31±0.56)mmol/L、(7.72±1.58)μU/mL、(4.87±0.26)%],APN、Omentin-1、HDL-C水平[(4.02±0.74)μg/mL、(174.09±35.20)μg/L、(0.82±0.16)mmol/L]均明显低于对照组[(12.36±1.56)μg/mL、(216.32±41.05)μg/L、(1.68±0.35)mmol/L],差异均有统计学意义(P均<0.001)。Pearson相关性分析显示,2型糖尿病患者血清circRNA LRP6水平与TNF-α、hs-CRP、FPG、FINS、HbA1c均成正相关(r=0.554、0.447、0.627、0.472、0.436,P均<0.001),与APN、Omentin-1、HDL-C均成负相关(r=-0.512、-0.572、-0.584,P均<0.001)。多因素logistic回归分析显示,FPG、FINS、circRNA LRP6是影响2型糖尿病发病的危险因素(P均<0.05),APN、HDL-C是影响2型糖尿病发病的保护因素(P均<0.05)。结论2型糖尿病患者血清circRNA LRP6表达升高,与炎症因子及糖脂代谢具有相关性,可作为预测2型糖尿病的生物标志物。

Objective To analyze the expression level of circular RNA-low density lipoprotein receptor-related protein 6(circRNA LRP6)in peripheral blood of patients with type 2 diabetes,and explore its correlation with inflammatory factors and glucose and lipid metabolism in patients.Methods A total of 96 patients with type 2 diabetes admitted to the Qinghai University Affiliated Hospital from January 2021 to April 2022 were taken as the observation group.Another 88 healthy volunteers were regarded as the control group.The expression level of circRNA LRP6 in serum was detected by real-time quantitative PCR(qRT-PCR);enzyme linked immunosorbent assay(ELISA)was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),high-sensitivity C-reactive protein(hs-CRP),adiponectin(APN)and Omentin-1 in serum;automatic biochemical analyzer was used to detect the levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and fasting blood sugar(FPG);automatic chemiluminescence immunoassay was used to detect fasting insulin(FINS)level;automatic glycated hemoglobin analyzer was applied to measure the level of glycated hemoglobin(HbA1c).The serum levels of circRNA LRP6,TNF-α,IL-6,hs-CRP,APN,Omentin-1,TC,TG,HDL-C,LDL-C,FPG,FINS,and HbA1c were compared between the two groups.Pearson correlation was used to analyze the correlation of circRNA LRP6 with inflammatory factors and glucose and lipid metabolism indexes.Multivariate logistic regression was used to analyze the influencing factors of type 2 diabetes.Results The levels of serum circRNA LRP6,TNF-α,IL-6,hs-CRP,TC,TG,LDL-C,FPG,FINS,and HbA1c in the observation group[(1.55±0.32),(12.55±1.72)pg/mL,(26.37±3.21)pg/mL,(13.15±2.98)mg/L,(5.84±0.61)mmol/L,(1.92±0.39)mmol/L,(3.85±0.46)mmol/L,(8.16±0.89)mmol/L,(13.25±1.96)μU/mL,(7.69±0.39)%]were significantly higher than those in the control group[(1.02±0.12),(9.10±1.15)pg/mL,(16.28±2.56)pg/mL,(8.31±1.96)mg/L,(4.15±0.53)mmol/L,(1.26±0.22)mmol/L,(2.29±0.19)mmol/L,(4.31±0.56)mmol/L,(7.72±1.58)μU/mL,(4.87±0.26%)];the levels of APN,Omentin-1,HDL-C[(4.02±0.74)μg/mL,(174.09±35.20)μg/L,(0.82±0.16)mmol/L]were significantly lower than those in the control group[(12.36±1.56)μg/mL,(216.32±41.05)μg/L,(1.68±0.35)mmol/L],the differences were statiscally significant(all P<0.001).Pearson correlation analysis showed that serum circRNA LRP6 level in patients with type 2 diabetes was greatly positively correlated with TNF-α,hs-CRP,FPG,FINS,and HbA1c(r=0.554,0.447,0.627,0.472,0.436,all P<0.001),and was greatly negatively correlated with APN,Omentin-1 and HDL-C(r=-0.512,-0.572,-0.584,all P<0.001).Multivariate logistic regression analysis showed that FPG,FINS,and circRNA LRP6 were risk factors affecting the incidence of type 2 diabetes(all P<0.05),and APN and HDL-C were protective factors affecting the incidence of type 2 diabetes(all P<0.05).Conclusion Serum circRNA LRP6 expression was increased in patients with type 2 diabetes,which was correlated with inflammatory factors and glucose and lipid metabolism,and could be used as a biomarker for predicting type 2 diabetes.