, Volume 28, Issue 9, pp 667–670

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

  • R. M. Wilson
  • C. A. Douglas
  • R. B. Tattersall
  • W. G. Reeves


Twenty-six Type 1 diabetic patients previously treated for 10–20 months with twice daily conventional bovine isophane insulin (containing at least 1000 ppm proinsulin) were changed to highly purified (<1 ppm proinsulin) bovine isophane for 6 months (Switch group). Insulin antibody levels fell significantly from a geometric mean of 14.9 to 9.1 μg/l. Thirty-two patients with newly diagnosed Type 1 diabetes were treated with the same highly purified bovine isophane insulin twice daily for 6 months (Starter group). Their insulin antibody levels rose from a geometric mean of 1.9 to 8.2 μg/l in contrast to values of 1.4 rising to 16.3 μg/l in an age and sex matched historical control group treated from diagnosis only with twice daily conventional bovine isophane insulin. Lipoatrophy at injection sites developed in three (9%) in the Starter group treated with highly purified bovine isophane compared to 7 (22%) of those on conventional bovine isophane. Insulin dose and diabetic control did not differ between the groups. Starterand 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 μg/l (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 


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  1. 1.
    Reeves WG (1980) Immunology of diabetes and insulin therapy. In: Thompson RA (ed) Recent advances in clinical immunology. Churchill Livingstone, Edinburgh, pp 183–220Google Scholar
  2. 2.
    Walford S, Allison SP, Reeves WG (1982) The effect of insulin antibodies on insulin dose and diabetic control. Diabetologia 22: 106–110PubMedCrossRefGoogle Scholar
  3. 3.
    Kurtz AB, Mathews JA, Mustaffa BE, Daggett PR, Nabarro JDN (1980) Decrease of antibodies to insulin, proinsulin and contaminating hormones after changing treatment from conventional beef to purified pork insulin. Diabetologia 18: 147–150PubMedCrossRefGoogle Scholar
  4. 4.
    Reeves WG (1981) Antibody production during insulin therapy — patterns of response and clinical sequels. In: Keck K and Erb P (eds) Basic and clinical Aspects of immunity to insulin. Walter De Gruyter, Berlin, pp 219–235Google Scholar
  5. 5.
    Reeves WG, Douglas CA (1982) C-peptide antibodies induced by bovine insulin therapy. Clin Exp Immunol 50: 171–177PubMedGoogle Scholar
  6. 6.
    Reeves WG, Kelly U (1982) Insulin antibodies induced by bovine insulin therapy. Clin Exp Immunol 50: 163–170PubMedGoogle Scholar
  7. 7.
    Peacock I, Taylor A, Tattersall RB, Douglas CA, Reeves WG (1983) Effects of new insulins of insulin and C-peptide antibodies, insulin dose and diabetic control. Lancet 1: 149–152PubMedCrossRefGoogle Scholar
  8. 8.
    Wilson RM, van der Minne P, Deverill I, Heller SR, Gelsthorpe K, Reeves WG, Tattersall RB (1985) Insulin dependence: problems with the classification of 100 consecutive patients. Diabetic Med 2: 167–172PubMedCrossRefGoogle Scholar
  9. 9.
    Reeves WG, Barr D, Douglas CA, Gelsthorpe K, Hanning I, Skene A, Wells L, Wilson RM, Tattersall RB (1984) Factors governing the human immune response to injected insulin. Diabetologia 26: 266–271PubMedCrossRefGoogle Scholar
  10. 10.
    Menard L, Dempsey ME, Blankstein LA, Aleyassine H, Wacks M, Soeldner JS (1980) Quantitative determination of glycosylated haemoglobin AI by agar gel electrophoresis. Clin Chem 26: 1598–1602PubMedGoogle Scholar
  11. 11.
    Peacock I (1984) Glycosylated haemoglobin: measurement and clinical use. J Clin Pathol 37: 841–851PubMedCrossRefGoogle Scholar
  12. 12.
    Heding LG, Larsson Y, Ludvigsson J (1980) The immunogenicity of insulin preparations. Antibody levels before and after transfer to highly purified porcine insulin. Diabetologia 19: 511–515PubMedGoogle Scholar
  13. 13.
    Holman RR, Steemson J, Darling P, Reeves WG, Turner RC (1984) Human ultralente insulin. Br Med J 228: 665–669CrossRefGoogle Scholar
  14. 14.
    Blundell TL, Cutfield JF, Cutfield SM, Dodson EJ, Dodson GG, Hodgkin DC, Mercola DA (1972) Three-dimensional atomic structure of insulin and its relationship to activity. Diabetes 21: (Suppl 2) 492–505PubMedGoogle Scholar
  15. 15.
    Reeves WG (1985) Immunological aspects of therapy. In: KGMM Alberti & LP Krall (eds) The Diabetes Annual. Elsevier, Amsterdam, pp 67–81Google Scholar
  16. 16.
    Reeves WG, Allen BR, Tattersall RB (1980) Insulin-induced lipoatrophy: evidence for an immune pathogenesis. Br Med J 280: 1500–1503PubMedCrossRefGoogle Scholar
  17. 17.
    Evans-Jones LG (1982) Lipoatrophy in a patient on highly purified beef insulin. Arch Dis Child 57: 638–639PubMedCrossRefGoogle Scholar
  18. 18.
    Jones GR, Statham B, Owens DR, Jones MK, Hayes TM (1981) Lipoatrophy and monocomponent porcine insulin. Br Med J 282: 190CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • R. M. Wilson
    • 1
  • C. A. Douglas
    • 1
  • R. B. Tattersall
    • 1
  • W. G. Reeves
    • 1
  1. 1.Departments of Immunology and MedicineUniversity Hospital, Queen's Medical CentreNottinghamUK

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