Decrease of antibodies to insulin, proinsulin and contaminating hormones after changing treatment from conventional beef to purified pork insulin

Abstract

Summary. The sera of 30 patients who had been treated with conventional beef insulin were tested for binding of insulin and other pancreatic hormones. All showed antibody binding of insulin, 29 binding of proinsulin, 29 binding of pancreatic polypeptide, two binding of glucagon but none of the sera bound vasoactive intestinal peptide or somatostatin. After changing therapy to highly purified pork insulin the binding capacity of sera for insulin and the other hormones was monitored for up to 35 months and a steady fall was found in nearly all cases. In eight of the patients conventional beef insulin treatment was resumed: in one month binding of insulin and of the other hormones increased back to the initial levels. In eighteen subjects who had only received highly purified pork insulin low levels of insulin binding were found with no binding of proinsulin or other hormones. The amounts of proinsulin and contaminating hormones in highly purified pork insulin are so low that they are not immunogenic; conventional beef insulin not only contains immunogenic amounts of proinsulin and the contaminating hormones pancreatic polypeptide and glucagon but also is more immunogenic than purified pork insulin.Key words: Insulin, proinsulin, pancreatic polypeptide, glucagon, antibodies.Conventional beef insulin preparations are more immunogenic than highly purified pork insulin [1]. They contain appreciable quantities of proinsulin, pancreatic polypeptide (PP), glucagon, somatostatin and vasoactive intestinal peptide (VIP) [2]. The greater immunogenicity of the conventional beef insulins has been attributed to the contaminants although other factors such as alteration or polymerisation of the insulin may be more important. A change of therapy from beef to purified pork insulin involves both a change in the species of insulin origin and an increase in purity as well as a possible change in the physical or chemical state of the insulin.In the present study the antibodies to insulin, proinsulin, PP, glucagon, somatostatin and VIP have been measured in patients treated with conventional beef insulin before and at intervals after a change to highly purified pork insulin. Materials and Methods PatientsThirty insulin treated patients were studied; 17 males and 13 females with an average age at the start of the study of 33 years (range 12-67) and an average duration of diabetes of 12 years (range 5-38).For at least six months before the start of this study all the patients were treated with twice daily soluble and isophane beef insulin with an average daily dose of 55 U (range 24-84): before this some had received other beef insulin preparations including beef/pork mixtures. None of the patients were regarded as "britfie" or insulin resistant, their antibody status was not known when they entered this study and none were taking immunosuppressive drugs or steroids.An initial blood sample was collected and then, after changeover to highly purified pork insulin (twice daily Leo Neutral | and Leo Retard | insulins), blood samples were col...

Immunogenicity of highly purified bovine insulin: a comparison with conventional bovine and highly purified human insulins

“…Previous studies have shown that changing from conventional bovine to highly purified porcine insulin (i. e. a change in both species and purity) reduces levels of insulin antibody and antibodies reactive with other pancreatic peptides and hormones [2,3,7,12]. However, we [7] found that a reduction in proinsulin contamination of bovine insulin to 20-40 ppm did not lower antibody levels in patients previously "immunised" with a conventional bovine preparation.…”

“…Not only are levels of insulin antibody higher but antibodies to C-peptide and other islet proteins are often present after using the conventional preparation [3][4][5][6]. We previously studied patients on conventional bovine soluble and isophane insulins who were transferred to equivalent bovine preparations purified to a proinsulin content of 20-40 ppm [7].…”

“…Starter and Switch groups were subsequently treated with semi-synthetic human isophane insulin for 6 months during which insulin antibody levels fell significantly from a geometric mean of 8.5 to 4.4 ~tg/1 (p< 0.001). We conclude that bovine insulin purified to less than 1 ppm proinsulin is significantly less immunogenic than its conventional proinsulin contaminated counterpart but even at this level of purity is still more immunogenic than human insulin of equivalent purity.Key words: Immunogenicity, Bovine insulin, Lipoatrophy, Insulin antibodies, Human insulin Previous studies [1][2][3] have shown that bovine insulin purified by sequential recrystallisation to > 1000ppm proinsulin (conventional bovine insulin) is much more immunogenic that its highly purified ( < 1 ppm proinsulin) porcine counterpart. Not only are levels of insulin antibody higher but antibodies to C-peptide and other islet proteins are often present after using the conventional preparation [3][4][5][6].…”

“…Key words: Immunogenicity, Bovine insulin, Lipoatrophy, Insulin antibodies, Human insulin Previous studies [1][2][3] have shown that bovine insulin purified by sequential recrystallisation to > 1000ppm proinsulin (conventional bovine insulin) is much more immunogenic that its highly purified ( < 1 ppm proinsulin) porcine counterpart. Not only are levels of insulin antibody higher but antibodies to C-peptide and other islet proteins are often present after using the conventional preparation [3][4][5][6].…”

Immunogenicity of intraperitoneal insulin infusion using programmable implantable devices

“…The insulin used in this study is a semi-synthetic human purified insulin and thus should show very little immunogenicity [24][25][26]. In this study neither the difference in insulin concentration nor the type of device used had any consequence in the evolution of AIA titres.…”