The effect of insulin antibodies on insulin dose and diabetic control

Abstract

Summary.In a single blind randomised cross-over study, 40 patients were changed from ordinary bovine to highly purified porcine insulins for a period of 6 months. Half were later rechallenged with bovine insulin. Sequential determinations of IgG insulin binding capacity for bovine insulin were correlated with insulin dose and diabetic control. After changing to highly purified insulins the following correlations were observed between percentage change in insulin dose and change in insulin binding capacity: at 2 months r = 0.35 (p < 0.05), at 4 months r = 0.38 (p < 0.02) and at 6 months r = 0.37 (p < 0.02). When the patients who showed substantial changes in HbA~ were removed from the analysis, the remaining 29 demonstrated a clearer relationship between these two variables (r = 0.56,p < 0.01). Removal of patients with a low initial insulin binding capacity left 18 patients with stable diabetes, and changes in insulin binding capacity and insulin dose showed an even closer correlation for this group (r = 0.77, p < 0.001). A similar degree of positive correlation was observed after rechallenge with bovine insulin. We conclude that the level of circulating insulin antibody affects the dose of insulin required to maintain stable diabetic control.Key words: Insulin, insulin antibody, diabetic control.Most patients treated with ordinary bovine insulins develop circulating insulin antibodies [1]. Higt/ly purified porcine insulins are much less immunogenic and patients changing to these insulins often experience a reduction in insulin requirement [2,3], a fall in circulating insulin binding capacity [4] and an increase in circulating levels of free insulin [5]. Although antibody mediated insulin resistance is unusual [6], injection site lipoatrophy is a common complication of the use of ordinary bovine insulins [7]. Other possible effects of insulin antibodies are less clear. Andersen [8] showed that the presence of antibodies was associated with a reduction in the honeymoon period independent of the level of diabetic control and the hypothesis that insulin antibody might 'buffer' the effect of circulating insulin [9] has not been substantiated. We report a study of the relationship between changes in insulin antibody, insulin dose and diabetic control in established diabetics changing from ordinary bovine soluble and isophane to highly purified porcine equivalents and the effects of rechallenge with the original insulins. Patients and MethodsThe practice of one hospital diabetologist was surveyed to identify all the patients aged between 16 and 65 years who had had diabetes for at least 3 years and had been treated regularly with ordinary bovine soluble and isophane insulins for at least that time. Those who were blind or pregnant or who had other serious medical or psychological illness were excluded. Fifty-nine of the 71 eligible patients consented to be studied and 40 completed the 18 month protocol. These 14 women and 26 men were aged between 16 and 64 years (mean 40 years). The age at diagnosis ranged from 2 to 5...

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.…”

“…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].…”

Insulin antibody determination: Theoretical and practical considerations

“…The production of insulin antibody is not only of academic interest for it does have a role in insulin allergy, injection site lipoatrophy [17] and some types of insulin resistance as well as having more subtle effects on the dose requirement, and on the pharmacokinetics of injected insulin [18][19][20][21]. Insulin-antibody complexes may have a deleterious effect in patients with vascular disease but there are insufficient data to be sure.…”

Breed differences in development of anti-insulin antibodies in diabetic dogs and investigation of the role of dog leukocyte antigen (DLA) genes

“…Alternatively, it is feasible that the AIA are having a partial neutralising effect on insulin activity, which would therefore require higher doses of insulin to maintain glycaemic control. In human diabetic patients, it has been shown that high levels of circulating AIA can affect the dose of insulin required to maintain glycaemic control and that by changing to a less immunogenic insulin there is a reduction in AIA and the dose of insulin required by the patient (Walford et al, 1982).…”