胰岛素样生长因子-1与手足口病重症化的相关性研究

Association between insulin like growth factor-1 and severe hand,foot and mouth disease

目的探讨胰岛素样生长因子-1(IGF-1)与手足口病(HFMD)患儿重症化的关联性。方法选取西安市儿童医院2020年6月至2022年7月收治住院的HFMD患儿共147例为病例组,根据《手足口病诊疗指南(2018年版)》,分为轻症组(99例)和重症组(48例)。选择本院儿童保健科同时期性别、年龄相匹配的健康体检45例儿童为对照组。收集各组儿童血清标本,采用ELISA方法检测IGF-1及其他实验室指标水平,并收集各组临床资料,计量资料采用t检验或非参数检验,计数资料采用χ^(2)检验,将可能影响HFMD重症化的指标进行多因素Logistic回归分析,并绘制受试者工作曲线(ROC)。结果病例组患儿急性期血清IGF-1水平[100.83(79.12,127.56)ng/ml]显著低于对照组[133.00(117.16,157.85)ng/ml](Z=-5.867、P<0.001),HFMD重症组患儿急性期血清IGF-1水平[88.83(70.97,100.77)ng/ml]显著低于轻症组[113.09(85.80,135.36)ng/ml](Z=-4.484、P<0.001),差异均有统计学意义;治疗后轻症组患儿恢复期血清IGF-1水平[140.25(123.45,154.34)ng/ml]较急性期[113.09(85.80,135.36)ng/ml]显著升高(Z=-5.473、P<0.001),重症组患儿恢复期血清IGF-1水平[(120.93±26.96)ng/ml]同样较急性期[(87.24±21.17)ng/ml]显著升高(t=-6.809、P=0.025),差异均有统计学意义;重症组患儿恢复期血清IGF-1水平[123.25(98.51,136.65)ng/ml]仍显著低于对照组,差异有统计学意义(Z=-2.552、P=0.011)。重症组与轻症组患儿白细胞计数(WBC)>15×10^(9)/L(χ^(2)=19.959、P<0.001)、空腹血糖(GLU)>8.3 mmol/L(χ^(2)=22.162、P<0.001)、热程(Z=-7.872、P<0.001)和出现神经系统症状(χ^(2)=21.475、P<0.001)病例占比差异均有统计学意义。ROC分析表明,IGF-1最佳临界值为105.83 ng/ml,灵敏度和特异度分别为55.6%和87.5%,曲线下面积为0.728。多因素Logistic回归分析显示,IGF-1<105.83 ng/ml(OR=9.182、95%CI:2.377~35.465、P=0.001)、WBC>15×10^(9)/L(OR=4.836、95%CI:1.473~15.871、P=0.009)、空腹血糖>8.3 mmol/L(OR=22.10^(9)、95%CI:2.736~178.664、P=0.004)和热程(OR=2.413、95%CI:1.706~3.413、P<0.001)均为HFMD重症化的危险因素。结论血清IGF-1水平与HFMD严重程度相关,血清IGF-1水平降低为HFMD病情进展的危险因素,IGF-1<105.83 ng/ml对HFMD重症化有预警价值。

Objective To investigate the association between insulin like growth factor-1(IGF-1)and severe disease in children with hand,foot and mouth disease(HFMD).Methods Total of 147 children with HFMD hospitalized in Xi’an Children’s Hospital from June 2020 to July 2022 were selected as HFMD case group,who were divided into mild disease group(99 cases)and severe disease group(48 cases)according to the Guidelines for Diagnosis and Treatment of HFMD(2018 edition);while 45 healthy children matching gender and age at the same period were selected as control group.Serum samples of children in each group were collected,and the levels of IGF-1 and other laboratory indicators were detected by enzyme-linked immunosorbent assay(ELISA)method.Clinical data of children in all group were collected.T-test or non-parametric test were used for measurement data,andχ^(2)test was used for counting data.Multiple Logistic regression analysis was performed for indicators that might affect the severity of HFMD,and the receiver operating curve(ROC)was plotted.Results Serum IGF-1 level of cases in case group[100.83(79.12,127.56)ng/ml]in acute stage was significantly lower than that of control group[133.00(117.16,157.85)ng/ml](Z=-5.867,P<0.001).Serum IGF-1 level of cases in severe disease group[88.83(70.97,100.77)ng/ml]was significantly lower in acute stage than that of mild disease group[113.09(85.80,135.36)ng/ml](Z=-4.484,P<0.001),with significant differences.After treatment,the level of serum IGF-1 in the mild disease group during convalescence[140.25(123.45,154.34)ng/ml]was significantly higher than that in the acute stage[113.09(85.80,135.36)ng/ml](Z=-5.473,P<0.001).Serum IGF-1 level[(120.93±26.96)ng/ml]of cases in severe disease group in the recovery stage was also significantly higher than that of the acute stage[(87.24±21.17)ng/ml](t=-6.809,P=0.025),with significant differences.The level of serum IGF-1 of cases in the severe disease group[123.25(98.51,136.65)ng/ml]was still significantly lower than that of the control group,with significant difference(Z=-2.552,P=0.011).White blood cell(WBC)>15×10^(9)/L(χ^(2)=19.959,P<0.001),fasting blood-glucose(GLU)>8.3 mmol/L(χ^(2)=22.162,P<0.001),heat range(Z=-7.872,P<0.001)and neurological symptoms(χ^(2)=21.475,P<0.001)were significantly different in severe disease group and mild disease group.ROC analysis showed that the optimal critical value of IGF-1 was 105.83 ng/ml,the sensitivity and specificity were 55.6%and 87.5%,respectively,and the area under the curve was 0.728.Multivariate Logistic regression analysis showed that IGF-1<105.83 ng/ml(OR=9.182,95%CI:2.377-35.465,P=0.001),WBC>15×10^(9)/L(OR=4.836,95%CI:1.473-15.871,P=0.009),fasting blood-glucose>8.3 mmol/L(OR=22.10^(9),95%CI:2.736-178.664,P=0.004),thermal range(OR=2.413,95%CI:1.706-3.413,P<0.001)were all risk factors for severe HFMD.Conclusions The level of serum IGF-1 is related to the severity of HFMD,and the decrease of serum IGF-1 level is a risk factor for the progression of HFMD disease,and IGF-1<105.83 ng/ml has early warning value for severe HFMD.