EFFECTS OF HUMAN INSULIN ON INSULIN BINDING ANTIBODY-PRODUCTION IN NONDIABETIC SUBJECTS
EFFECTS OF HUMAN INSULIN ON INSULIN BINDING ANTIBODY-PRODUCTION IN NONDIABETIC SUBJECTS
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DOI：
10.2337/diacare.15.1.124
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发表时间：
1992-01-01
期刊：
影响因子：
16.2
通讯作者：
ALBERTI, KGMM
中科院分区：
文献类型：
--
作者：
DAVIS, SN;THOMPSON, CJ;ALBERTI, KGMM
目的：验证人胰岛素可能具有低免疫原性和短期暴露可能不会引起内源性胰岛素抗体产生的假设。研究设计和方法：随机双盲前瞻性研究。收集胰岛素结合抗体的血清样本，并通过敏感的免疫化学试验进行测量。研究对象为7名从未接受过外源性胰岛素治疗的健康非糖尿病患者。每个受试者每月接受6次人胰岛素注射。在四种情况下，同时使用常规胰岛素和NPH胰岛素。在另外两种情况下，单独使用NPH或常规胰岛素。结果- 4次注射后，平均+/- SE基础胰岛素抗体水平（1.2 +/- 0.2 mu-g/L）上升至4.5 +/- 0.8 mu-g/L的最高水平。此后，抗体水平下降到研究结束时的2.5 +/- 0.3 mu-g/L。这代表了非常显著的总体增长（P < 0.001）。对照组6名胰岛素依赖型糖尿病患者在同一时间内接受人胰岛素治疗，胰岛素抗体浓度没有变化（2.8 +/- 0.7-2.7 +/- 0.6 μ g/L）。结论：这些结果表明，皮下给药的人胰岛素制剂可能比以前认为的更具免疫原性。抗原反应是迅速的，因为在非糖尿病患者中，只需四次皮下注射就足以产生胰岛素抗体水平，这与在接受慢性胰岛素替代治疗的胰岛素依赖糖尿病患者中观察到的水平相似。
OBJECTIVE - To test the hypothesis that human insulin may have a low immunogenicity and that short-term exposure may not cause endogenous insulin antibody production.RESEARCH DESIGN AND METHODS - Randomized double-blind prospective study. Serum samples collected for insulin binding antibodies and measured by a sensitive immunochemical assay. Subjects were seven healthy nondiabetic patients who had never received exogenous insulin. Each subject received 6 separate monthly injections of human insulin. On four occasions, both regular and NPH insulin were administered. On the other two occasions, either NPH or regular insulin was administered alone.RESULTS - Mean +/- SE basal insulin antibody levels (1.2 +/- 0.2-mu-g/L) increased to a maximal level of 4.5 +/- 0.8-mu-g/L after four injections. Thereafter, antibody levels declined to an end-of-study value of 2.5 +/- 0.3-mu-g/L. This represented a highly significant overall increase (P < 0.001). A control group of six insulin-dependent diabetic subjects treated with human insulin over the same period as the test subjects demonstrated no change in insulin antibody concentrations (2.8 +/- 0.7-2.7 +/- 0.6-mu-g/L).CONCLUSIONS - These results suggest that human insulin preparations, when administered subcutaneously, may be more immunogenic than previously considered. The antigenic response was rapid, because only four subcutaneous injections were sufficient to produce insulin antibody levels in nondiabetic patients similar to those observed in insulin-dependent diabetic patients receiving chronic insulin replacement therapy.