Abstract
We report a 66-year-old female patient, who showed an unusually high serum level of immunoreactive proinsulin (IRP) after treatment with bovine-porcine mixed insulin. On the 14th day of secondary heterologous insulin therapy, total-IRI, -CPR and-IRP levels in serum were 428μU/ml, 128 ng/ml and 49.3 ng/ml, respectively. Most of IRI and CPR activity consisted of antibodybound forms. Direct and competitive studies demonstrated that antibodies in the serum did not recognize the free C-peptide and matched only a little of the C-peptide portion of proinsulin (proinsulin specific antibody). However, insulin antibody level reached 64.3% in insulin-binding capacity and 1008 ng/ml, in antibody index. These antibodies were dissociated more easily from bound insulin by the addition of variable concentrations of cold porcine proinsulin, compared with antibodies from 7 other insulin-treated diabetic patients. After acid-ethanol extraction, most of the CPR and IRI activity corresponded to the proinsulin marker in Bio-Gel P 30 column analysis. This case has received 3 series of insulin treatment sufficiently recovering her metabolic state after each series to the extent that she did not need exogenous insulin administration for at least several months. After the 2nd series with heterologous insulin, insulin antibody and proinsulin levels in serum gradually decreased in parallel. Insulinoma, renal failure, insulin autoimmune syndrome and autosomal dominant familial hyperproinsulinemia, accompanied by hyperproinsulinemia, could be ruled out from laboratory findings and the screening of serum IRP levels in her family. The hyperproinsulinemia in this case was therefore likely to be due to insulin antibody which has high affinity for proinsulin. During the last series with human (recombinant DNA) insulin, she was brought under a good level of control without any remarkable rise of proinsulin or insulin antibody levels in her serum. She was since maintained a good condition without any hypoglycemic agents. In this case therefore, homologous insulin is better than the heterologous type with respect to antibody production.
