重组人胰岛素治疗2型糖尿病免疫原性研究

目的探讨重组人胰岛素治疗2型糖尿病的免疫原性及其临床意义。方法应用放射免疫法检测179例重组人胰岛素治疗的2型糖尿病患者及429例未用胰岛素治疗的2型糖尿病患者胰岛素抗体（INS-Ab）的阳性率,并分析INS-Ab阳性患者的临床特征及其危险因素。结果 （1）重组人胰岛素治疗组中INS-Ab阳性率为36.31%,而未用重组人胰岛素组INS-Ab阳性率为0.23%,差异具有统计学意义（χ2=166.19,P=0.000）。（2）Logistic回归分析显示在应用重组人胰岛素的患者中INS-Ab阳性的危险因素分别为胰岛素治疗时间（OR=1.201,P=0.006）及糖尿病病程（OR=1.07,P=0.004）。应用重组人胰岛素半年以上、糖尿病病程5年以上并已接受重组人胰岛素治疗时,INS-Ab阳性率明显升高（P〈0.05）。重组人胰岛素治疗组中,INS-Ab阳性组HOMR-IR明显高于INS-Ab阴性组（18.48±21.58 vs.6.90±14.39,t=3.68,P=0.000）,高胰岛素血症组INS-Ab阳性率也明显高于无高胰岛素血症组（59.26%vs.20.99%,χ2=33.684,P=0.000）。（3）INS-Ab阳性患者空腹胰岛素及餐后2 h胰岛素水平均明显高于INS-Ab阴性者（P〈0.05）,低血糖发生次数明显高于阴性者（Z=-6.109,P=0.000）。（4）INS-Ab阳性组糖化血红蛋白达标率明显低于阴性组（χ2=4.422,P=0.035）。（5）诺和灵30R、甘舒林30R及优泌林30R胰岛素抗体阳性率分别为37.25%、38.46%、28.13%,差异无统计学意义（χ2=0.948,P=0.623）。结论 （1）重组人胰岛素治疗2型糖尿病仍具有免疫原性,在应用重组人胰岛素的患者中重组人胰岛素应用超过半年、低血糖频发、糖尿病病程5年以上的应及时检测INS-Ab。（2）已经使用重组人胰岛素的糖尿病患者也应常规查血清胰岛素水平,及时发现高胰岛素血症及免疫性胰岛素抵抗。（3）INS-Ab是胰岛素抵抗的危险因素,是影响糖尿病患者糖化血红蛋白达标率的因素之一。

Study about the immunogenicity of recombinant human insulin in treatment of type 2 diabetes meilitus

Objective To study the immunogenicity and its clinical significance of recombinant human insulin during in treatment of type 2 diabetes mellitus （T2DM） patients. Methods Using radioimmunoassay to detect insulin antibody of 179 T2DM patients treated with recombinant human insulin and 429 patients without insulin treatment, to compare the antibody positive rate, and to analyze the clinical features of antibody-positive patients and the risk factors for insulin antibodies. Results （1） The INS-Ab positive rate of insulin-treatment group was 36.31%, while 0.23% in without-using insulin group. The difference was statistically significant （x2= 166.19, P=0.000）. （2） Logistic regression analysis showed that insulin-treated duration （OR= 1.201, P=0.006）, DM course （OR= 1.07, P=0.004） were the risk factors for insulin antibodies in insulin-treated patients. While the application of recombinant human insulin was more than half year and the DM course was more than five years, the positive rate was significantly higher （P〈0.05）. HOMR-IR in INS-Ab positive patients was significantly higher than in INS-Ab negative ones（18.48±21.58 vs. 6.90±14.39, t=3.68, P=0.000）. The INS-Ab positive rate of patients with hyperinsulinemia was 78.43%, while 19.53% of patients without hyperinsulinemia, the difference was significantly（x^2=33.684, P=0.000）. （3） Fasting insulin and 2-hour postprandial insulin levels in INS-Ab positive patients were significantly higher than in INS-Ab negative ones（P〈 0.05）. The occurrence of hypoglycemia in INS-Ab positive patients was significantly higher than in INS-Ab negative ones（Z=-6.109, P=0.000）. （4） The compliance rate of glycated hemoglobin in INS-Ab positive group was significantly lower than in INS-Ab negative group（x^2=4.422, P=0.035）. （5） The INS-Ab positive rate ofNovolin 30R, Gan Shulin 30R and Humulin 30R were 37.25%, 38.46%, 28.13%, respectively. The difference was not statistically significant （x^2= 0.948, P=0.623）. Conclusions Recombinant human insulin to treat T2DM has immunogenicity, when the application of recombinant human insulin is more than half year in insulin-treated patients, hypoglycemia happened frequently, and the DM course is more than five years, it is time to detect insulin antibody. Diabetic patients who have used recombinant human insulin should be routinely check serum insulin levels to discover hyperinsulinemia and immune insulin resistance. INS-Ab is a risk factor for insulin resistance, and it is one of the impactions on the compliance rate of glycated hemoglobin in type 2 diabetes.