| Objective:with the gradual progress of human beings into the aging society,combined with the factors such as environmental degradation,the rhythm of life increases and so on,the number of diabetic patients is increasing.Since 1922,exogenous insulin was used to treat diabetes for the first time.It is almost irreplaceable because of its definite curative effect and minimal adverse reaction.As scientists gradually improve the effect of exogenous insulin,and reduce the side effects,the development of insulin experienced a phased change:the first generation of animal insulin,the second generation of biosynthetic insulin,including semi-synthetic insulin and recombinant human insulin,third-generation insulin analogues.In clinic,animal insulin has been phased out because of its high immunogenicity.The insulin analogues are widely used as a substitute for recombinant human insulin,because they are more accord with physiological human insulin spectrum.With extensive use of the application of exogenous insulin,there is a gradual increase in adverse reactions,such as insulin resistance,allergy and hypoglycemia and so on.Since 1959,Besron and Yalow for the first time to sensitively detect insulin antibody with 125 iodinated insulin.Scholars have paid more and more attention to the immunogenicity of insulin.It is gradually recognized that exogenous insulin induces the production of insulin antibodies in the circulation,which may be an important factor in changing the bioavailability and pharmacokinetics of insulin and inducing a series of immune responses.It is also one of the important reasons to promote the regeneration of exogenous insulin.In the past,many experiments have proved that both animal insulin and recombinant human insulin have potential immunogenicity.The only way to discover the immunogenicity of a protein is to review the immunoreaction of it with a retrospective review.Through observing the difference in the positive rate of insulin antibodies between T2DM patients treated with insulin analogues and T2DM patients not treated with insulin,the study expounded the immunogenicity of insulin analogues,analyzed the related factors that affect the positive antibodies of insulin,and explored the risk factors of insulin antibody formation,so as to guide clinical medication.Method:1.Object of study:the study selected 183 type 2 diabetic patients treated with insulin analogues(Treatment group)and 472 type 2 diabetes without exogenous insulin treatment(Non treatment group),The treatment group was divided into insulin antibody positive group and insulin antibody negative group according to the results of insulin antibody test.2.Research method:the difference of positive rate of insulin antibody between treatment group and non treatment group was compared.The differences in sex,age,history of diabetes,BMI,time,dose,dose,TC,TG,HDL,LDL,ALT,AST,BUN,Cr,UA,TSH,FT3,TSH,in the group of insulin antibody positive groups and negative groups were analyzed.The risk factors for insulin antibody positive were identified.3.Statistical methods:data analysis has used SPSS21.0 statistical analysis software.The quantitative data was described by mean number+standard deviation(?x±s)or median(interquartile range)(M(QR)).The groups were compared with two independent sample t test or two sample Wilcoxon rank sum test;qualitative data was described with percentage number,and chi square test was used among groups.Logistic regression analysis was used to analyze the influencing factors of IAA in patients treated with insulin analogues.P<0.05 as a statistical difference.Result:1.There was no significant difference between the two groups in the treatment group and the non treatment group.Comparison of the positive rate of IAA between the treatment group and the non treatment group:there were37 cases of IAA positive patients in insulin analogue treatment group,the positive rate of IAA was 20.22%(37/183);and treatment without exogenous insulin group only 6 cases were IAA positive,the positive rate of IAA was1.27%(6/472).The difference between the positive rate of IAA in the two groups were statistically significant(χ~2=77.182,P=0.000).2.The factors may affect the insulin antibody in the IAA positive group and the IAA negative group were compared(Table 2),there were significant statistical differences between the positive and negative groups of which age(t=-3.215,P=0.002),duration of diabetes(Z=-7.402,P=0.000),duration of insulin use(year)(Z=-3.371,P=0.001),insulin dose(Z=-5.624,P=0.000),systolic blood pressure(SBP)(Z=-2.461,P=0.014),diastolic b l o o d p r e s s u r e(D B P)(Z=-4.5 7 1,P=0.0 0 0),H b A 1 c s t a n d a r d rate(56.2%(82/146)&8.1%(3/37),χ~2=-27.407,P=0.000).3.Analysis of related risk factors of IAA:In insulin analogue treatment group,IAA was the dependent variable,the patients’age,duration of diabetes,duration of insulin use(years),insulin analogue dose,systolic blood pressure,diastolic blood pressure and Hb A1c were independent variables.The assignment of 7 possible risk factors was shown in Table 3.Logistic regression analysis showed that the risk factors of the IAA positive were duration of diabetes(OR=17.376,95%CI:5.422-55.680,P=0.000),insulin analogue dose(OR=3.089,95%CI:1.555-6.139,P=0.001),HbA1c(OR=19.921,95%CI:3.444-115.242,P=0.001),diastolic pressure(OR=0.021,95%CI:0.001-0.679,P=0.029)(Table 4).4.Duration of diabetes and insulin analogue dose were two of the IAA positive risk factors in the logistic regression analysis which have multiple groups assignment were further analyzed,rough estimated the distinct differences nodes in two risk factors.divided the duration of diabetes into 4groups according to:1=to 1 years,2=2 to 5 years,3=6 to 9 years,and 4=10years.The IAA positive rate in different groups were compared(Fig.1).In the four groups of diabetes,the positive rate of insulin antibody from the third groups was statistically different from that of the first group.The risk of IAA positive increased more than 6 years of illness.The insulin analogue dose group was divided according to:1=<20U/d,2=20~U/d,,3=30~U/d,,4=40~U/d,and the IAA positive rate of different insulin analogs were compared(Figure 2).In the four groups of insulin analogues,the positive rate of insulin antibody from the fourth groups was significantly different from that of the f i r s t g r o u p.T h e r i s k o f I A A p o s itive was higher when insulin analogues were used more than 40 U/d.Conclusion1.Insulin analogues still have immunogenicity in the treatment of type 2diabetes.2.More longer the duration of diabetes,more greater the use of insulin analogues and the failure of glycated hemoglobin made the higher the risk of insulin antibody positive.The positive rate of insulin antibody increased when diastolic blood pressure reduced.3.In patients treated by insulin analogues who suffer from diabetes for more than 6 years,used insulin analogues over 40U/d,and glycosylated hemoglobin control did not reach the standard,diastolic pressure is low,IAA should be detected in time. |
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