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

Diabetologia, Feb 1980

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.

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

Decrease of Antibodies to Insulin, Proinsulin and Contaminating Hormones after Changing Treatment from Conventional Beef to Purified Pork Insulin A. B. Kurtz 0 J. A. Matthews 0 B. E. Mustaffa 0 P. R. Daggett 0 J. D. N. N a b a r r o 0 0 Department of Nuclear Medicine and Cobbold Laboratories, Thorn Institute of Clinical Science, The MiddlesexHospital Medical School , London, England Summary. T h e sera of 30 patients who h a d b e e n t r e a t e d with conventional b e e f 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 n o n e of the sera b o u n d vasoactive intestinal peptide or somatostatin. A f t e r changing t h e r a p y to highly purified p o r k insulin the binding capacity of sera for insulin and the other horm o n e s was m o n i t o r e d for up to 35 m o n t h s and a steady fall was f o u n d in nearly all cases. In eight of the patients conventional b e e f insulin t r e a t m e n t was resumed: in one m o n t h binding of insulin and of the o t h e r h o r m o n e s increased b a c k to the initial levels. In eighteen subjects w h o h a d only received highly purified p o r k insulin low levels of insulin binding were found with no binding of proinsulin or other h o r m o n e s . T h e a m o u n t s of proinsulin and contaminating h o r m o n e s in highly purified p o r k insulin are so low that they are not immunogenic; conventional b e e f insulin not only contains i m m u n o g e n i c a m o u n t s of proinsulin and the contaminating horm o n e s pancreatic p o l y p e p t i d e and glucagon but also is m o r e i m m u n o g e n i c than purified p o r k insulin. Insulin; proinsulin; pancreatic p o l y p e p tide; glucagon; antibodies - Conventional b e e f insulin p r e p a r a t i o n s are m o r e i m m u n o g e n i c than highly purified p o r k insulin [ 1 ]. T h e y contain appreciable quantities of proinsulin, pancreatic p o l y p e p t i d e (PP), glucagon, somatostatin and vasoactive intestinal peptide (VIP) [ 2 ]. T h e g r e a t e r immunogenicity of the conventional b e e f insulins has b e e n attributed to the contaminants although o t h e r factors such as alteration or p o l y m e r isation of the insulin m a y be m o r e important. A change of t h e r a p y f r o m b e e f to purified p o r k insulin involves b o t h 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 V I P have b e e n m e a s u r e d in patients t r e a t e d with conventional beef insulin b e f o r e and at intervals after a change to highly purified p o r k insulin. Materials and Methods Patients Thirty 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 collected at approximately monthly intervals for six months and thereafter at 4-6 monthly intervals. The group was followed for an average of 30 months (range 23-35): twenty two patients have continued on the purified pork insulin while eight patients, at their own request, have changed back to conventional beef insulin after an average of 8.4 months (range 6-12) on the purified pork insulin. For comparison with this group of patients the sera from 18 subjects never treated with other than highly purified pork insulin were checked for antibody binding. This group had been on insulin for an average of 13 months (range 2-24). Blood samples were collected at routine diabetic clinic visits and the plasma or serum stored deep-frozen until studied. For all the ligands tested the same general method was used to measure antibody binding. Ten ul of plasma was incubated for 24 h 100 :,],I - m - ~ C ,e,,i iF | i ! 9 9 ~, J ~ . ~ 9 N i l I ,ON \0"1 D | I I "~ ",ol 9 "..9 o" 9 'lJl ,ON] \ ~ ",Ol IKI '~1 t 9 l at 4 ~C with 150 Ixl of 0,04 re9 sodium phosphate buffer, pH 7.5, containing sodium chloride 0.15mol/1, bovine serum albumin 0.5 g/l, bovine gamma globulin 0.25 g/1 and 125I labelled ligand, approximately 200,000 cpm/ml. Then foll (...truncated)


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A. B. Kurtz, J. A. Matthews, B. E. Mustaffa, P. R. Daggett, J. D. N. Nabarro. Decrease of antibodies to insulin, proinsulin and contaminating hormones after changing treatment from conventional beef to purified pork insulin, Diabetologia, 1980, pp. 147-150, Volume 18, Issue 2, DOI: 10.1007/BF00290492