8-isoPGF2α、Metrnl、LC3B-Ⅱ/LC3B-Ⅰ与T2MD患者血糖在目标范围内时间的相关性及预测糖尿病周围神经病变的价值

Correlation between 8-isoPGF2α,Metrnl,LC3B-Ⅱ/LC3B-Ⅰand time in range in T2MD patients and their value for predicting diabetes peripheral neuropathy

目的探讨8-异前列腺素F2α(8-isoPGF2α)、镍纹样蛋白(Metrnl)、微管相关蛋白3B-Ⅱ(LC3B-Ⅱ)/微管相关蛋白-Ⅰ(LC3B-Ⅰ)与2型糖尿病(T2MD)患者血糖在目标范围内时间(TIR)的相关性及对糖尿病周围神经病变(DPN)预测价值。方法选取2020年5月至2022年10月新乡医学院第一附属医院收治的187例T2DM患者进行前瞻性研究,根据是否合并DPN分为DPN组(n=48)和无DPN组(n=139)。比较两组患者及根据TIR四分位数分组的患者8-isoPGF2α、Metrnl、LC3B-Ⅱ/LC3B-Ⅰ水平,采用Pearson相关性分析8-isoPGF2α、Metrnl、LC3B-Ⅱ/LC3B-Ⅰ与TIR相关性,采用多因素Logistic回归分析DPN的相关影响因素;绘制受试者工作特征曲线(ROC)评价8-isoPGF2α、Metrnl、LC3B-Ⅱ预测DPN的价值。结果DPN组患者的TIR为(51.43±7.68)%,明显低于无DPN组的(56.94±8.12)%,差异有统计学意义(P<0.05);DPN组患者的8-isoPGF2α、Metrnl分别为(162.78±51.33)pg/mL、(259.18±74.42)pg/mL,明显高于无DPN组的(129.56±43.00)pg/mL、(208.37±65.61)pg/mL,LC3B-Ⅱ/LC3B-Ⅰ为0.89±0.27,明显低于无DPN组的1.15±0.31,差异均有统计学意义(P<0.05);根据TIR第25、50、75百分位数将全部患者分为Q1~Q4四组,8-isoPGF2α、Metrnl在Q4组最低,LC3B-Ⅱ/LC3B-Ⅰ在Q4组最高;8-isoPGF2α、Metrnl随着TIR降低逐渐升高,LC3B-Ⅱ/LC3B-Ⅰ随着TIR降低而降低,四组间比较差异均有统计学意义(P<0.05);Pearson相关性分析结果显示,8-isoPGF2α、Metrnl与TIR呈显著负相关(r=-0.786、-0.665,P<0.01),LC3B-Ⅱ/LC3B-Ⅰ与TIR呈显著正相关(r=0.711,P<0.01);多因素Logistic回归分析结果显示,TIR、LC3B-Ⅱ/LC3B-Ⅰ是DPN的独立相关保护因素(P<0.05),8-isoPGF2α、Metrnl是DPN的独立相关危险因素(P<0.05);ROC分析结果显示,单一指标中,Metrnl预测DPN的AUC最大(0.830),特异度最高(87.05%),8-isoPGF2α+Metrnl+LC3B-Ⅱ预测DPN的AUC为0.923(95%CI:0.875~0.957),大于Metrnl,预测敏感度为87.50%,特异度为85.61%(P<0.05)。结论8-isoPGF2α、Metrnl、LC3B-Ⅱ/LC3B-Ⅰ与T2MD患者TIR有关,均是患者并发DPN的预警因素。联合检测三者能为临床分层管理和早期识别DPN高风险人群提供参考。

Objective To investigate the correlation between 8-isoprostaglandin F2α(8-isoPGF2α),nickel pat-tern protein(Metrnl),microtubule-associated protein 1 light chain 3B-Ⅱ(LC3B-Ⅱ)/microtubule-associated protein 1 light chain 3B-Ⅰ(LC3B-Ⅰ)and time in range in patients with type 2 diabetes mellitus(T2MD)and their predictive value on diabetic peripheral neuropathy(DPN).Methods A prospective study was conducted on 187 patients with T2DM admitted to the First Affiliated Hospital of Xinxiang Medical University from May 2020 to October 2022.The pa-tients were divided into DPN group(n=48)and non-DPN group(n=139)according to whether they had DPN.The levels of 8-isoPGF2α,Metrnl,LC3B-Ⅱ/LC3B-Ⅰwere compared between the two groups and among patients grouped ac-cording to TIR quartiles.Pearson correlation analysis was used to analyze the correlation between 8-isoPGF2α,Metrnl,LC3B-Ⅱ/LC3B-Ⅰand TIR,and multiple factor logistic regression analysis was used to analyze the related factors of DPN.The receiver operating characteristic curve(ROC)was used to evaluate the value of 8-isoPGF2α,Metrnl,LC3B-Ⅱin predicting DPN.Results The TIR of patients in the DPN group was(51.43±7.68)%,which was significantly lower than(56.94±8.12)%of patients in the non-DPN group(P<0.05).The levels of 8-isoPGF2αand Metrnl in the DPN group were(162.78±51.33)pg/mL and(259.18±74.42)pg/mL,respectively,which were significantly higher than(129.56±43.00)pg/mL and(208.37±65.61)pg/mL in the non-DPN group,respectively;the LC3B-Ⅱ/LC3B-Ⅰratio was 0.89±0.27,which was significantly lower than 1.15±0.31 in the non-DPN group;the differences were statistically signifi-cant(P<0.05).According to the 25th,50th,and 75th percentiles of TIR,the patients were divided into four groups:Q1 to Q4.The level of 8-isoPGF2αand Metrnl was the lowest in Q4,while the LC3B-Ⅱ/LC3B-Ⅰratio was the highest in Q4;the levels of 8-isoPGF2αand Metrnl gradually increased with the decrease of TIR,while the LC3B-Ⅱ/LC3B-Ⅰra-tio decreased with the decrease of TIR;there were statistically significant differences in the three indexes among the four groups(P<0.05).Pearson correlation analysis showed that 8-isoPGF2αand Metrnl were significantly negatively corre-lated with TIR(r=-0.786,-0.665,P<0.01),and LC3B-Ⅱ/LC3B-Ⅰwas positively correlated with TIR(r=0.711,P<0.01).The results of multivariable logistic regression analysis showed that TIR and LC3B-Ⅱ/LC3B-Ⅰwere indepen-dent protective factors for DPN(P<0.05),while 8-isoPGF2αand Metrnl were independent risk factors for DPN(P<0.05).ROC analysis showed that among single indicators,Metrnl had the highest AUC(0.830)and specificity(87.05%)for predicting DPN,while 8-isoPGF2α+Metrnl+LC3B-Ⅱhad an AUC of 0.923(95%CI:0.875-0.957)for predicting DPN,which was greater than that of Metrnl,with a sensitivity of 87.50%and specificity of 85.61%(P<0.05).Conclusion 8-isoPGF2α,Metrnl,LC3B-Ⅱ/LC3B-Ⅰare related to TIR of T2MD patients,and all of them are early warning factors of DPN.Combined detection of these three factors can provide a reference for clinical stratification man-agement and early identification of high-risk populations with DPN.