The Immunogenic Properties of Highly Purified Insulin Preparations. The Clinical Importance of Insulin-Binding Antibodies

Abstract

Twenty-four diabetic patients were treated with porcine protamine-insulin (NPH-insulin) containing 7\p=n-\13 mmol proinsulin per mol insulin and 27 diabetic patients were treated with porcine protamine-insulin (HP-insulin) containing 0.36 mmol proinsulin per mol insulin. 75 % of the patients treated with NPH-insulin and 15 % of the patients treated with HP\x=req-\ insulin formed detectable insulin-binding antibodies. The difference in the antibody titre in the two groups was significant. As a group, patients treated with HP-insulin did not have a significant rise in the plasma insulin-binding capacity when compared to pre-treatment values. When comparing patients with antibodies and patients without detectable antibodies no difference in the degree of regulation could be demonstrated between the two groups. Young patients with antibodies had a higher insulin requirement per kg per day than patients without detectable antibodies.Among patients in remission those without detectable antibodies had a longer remission period than those with antibodies. Apart from the difference in antibody formation and hence a different distribution in the groups compared, the patients treated with NPH-insulin and HP-insulin did not differ with regard to the degree of regulation, the insulin requirement or the duration of the remission period.Commonly available recrystallized insulin preparations contain 1-2 per cent proinsulin (Steiner et al. 1968; Chance 8c Ellis 1969). The molecular weight of proinsulin is about 150 per cent of that of insulin (Frank 8c Veros 1968), and while the insulins generally used differ from human insulin in only one amino

Insulin immunogenicity in pregnancy: maternal and fetal studies

“…These results agree with those of studies on non-pregnant diabeticpatients [20,24,29,31]. Furthermore, very low levels of insulin antibodies have been reported in newly diagnosed diabetic patients treated with highly purified porcine insulin [32,33]. Our results have shown that it is necessary not only to use highly purified but also porcine, rather than bovine insulin, if insulin antibody formation is to be minimised.…”

“…The protamine is unlikely to contribute towards the immunogenicity because its occurrence in highly purified porcine insulin (Leo retard or Insulatard) is not significantly immunogenic. It is possible that the combination of an acidic insulin (soluble) with a particulate insulin (PZI) may enhance the immunogenicity [32].…”

Persistent insulin secretion, assessed by plasma C-peptide estimation in long-term juvenile diabetics with a low insulin requirement

“…The prevalence of insulin antibodies in these patients was rather low, viz. 45% as compared to 75% in patients treated with porcine NPH insulin preparations in Andersen's study [3]. But it must be remembered that all patients in the present material were treated with highly purified porcine insulin for 1-2 years.…”

“…Insulin antibodies have been shown to be of significance to the duration of the remission period (the period of considerable endogenous insulin production) in juvenile diabetics [3]. It has also been suggested that insulin antibodies may cause beta-cell exhaustion [3,11].…”

Insulin autoantibodies are associated with islet cell antibodies; their relation to insulin antibodies and B-cell function in diabetic children

“…Insulin antibodies in response to exogenous insulin is a common phenomenon, Their clinical importance is unclear but studies have indicated that insulin antibodies have a negative effect on the metabolic balance and on the duration of the metabolically stable period early after diagnosis, the so-called partial remission [12][13][14]. It has been shown that even very low concentrations of insulin antibodies are related to a diminished residual insulin secretion and an increased requirement of insulin at 9 months duration of diabetes [15].…”