The Immunogenicity of Insulin Preparation. Antibody Levels before and after Transfer to Highly Purified Porcine Insulin

Ninety-two insulin-dependent diabetics (aged 4–20 years, mean±SD: 13±4) with a duration of diabetes from 2 to 17 years (7±3) were transferred from Lente or NPH (5 × crystallised insulin) to Monotard insulin (highly purified insulin). Total serum immunoreactive insulin levels and concentrations of antibodies against insulin, porcine proinsulin, a-component and pancreatic polypeptide were determined prior to [I] and at a mean of 220 [II], 460 [III], 830 [IV], and 1170 [V] days after the change. All but two subjects had insulin antibodies (IgG) at the start, with a mean value of 2864 μU/ml. There was a significant fall in the mean insulin antibody level between [I] and [II] to 2165 μU/ml (p<10-7), followed by an increase between [II] and [III] whereafter a slight decrease was observed being significant between [III] and [IV], as well as between [IV] and [V] (p<0.05); some patients showed a constant fall over the entire period, while others showed fluctuations. Total serum insulin showed a similar pattern, with a mean value of 1141 μU/ml at [I] declining to 522 μU/ml at [V]. The percentage fall between [I] and [V] was greater (54%) than that in the insulin antibodies (30%). Antibodies against acomponent, proinsulin and pancreatic polypeptide were present in 96%, 72% and 41% of the patients respectively before the change in therapy. There was a decline in these antibodies between each sampling (p values between <10-3 and 10-8) and, at the end of the investigation antibodies against a-component were above the detection limit in only 4 patients, and none of the patients showed antibodies against proinsulin or pancreatic polypeptide. Thus, removal of the impurities, including the hormonal contaminants of insulin, leads to a slow fall in antibodies to insulin and a much faster disappearance of antibodies against acomponent, proinsulin and pancreatic polypeptide.