Skip to main content
SpringerLink
Log in

Insulin Allergy

Epidemiology and Management

  • Practical Therapeutics
  • Published:
Clinical Immunotherapeutics Aims and scope Submit manuscript

Summary

The incidence of insulin allergy has decreased but has not been eliminated with the increased use of recombinant human insulin. A search of the literature for 1985 to 1993 identified a number of articles reporting hypersensitivity reactions to human insulin. Most of the reactions were local and occurred in patients allergic to insulins of animal origin who had been changed to human insulin. Nevertheless, primary allergy, sometimes severe, to human insulin and to the insulin additives protamine and zinc have been described.

We have to be able to manage diabetic patients with such reactions. It is essential to establish an accurate diagnosis of allergy to insulin itself or to its additives. Skin cutaneous tests, in association with clinical history, have a high specificity for the diagnosis of insulin allergy. The clinical relevance of anti-insulin immunoglobulin E and total immunoglobulin antibody production to insulin is speculative.

The patient should be treated with the least allergenic insulin, but if reactions still occur, it will be necessary to carry out desensitisation or other alternatives to induce tolerance to insulin. Additional investigations are necessary to understand the immunogenetics, mechanisms and implications of antibody responses to insulin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wess ME. Drug allergy. Med Clin North Am 1992; 76: 857–82

    Google Scholar 

  2. Brogden RN, Heel RC. Human insulin: a review of its biological activity, pharmacokinetics and therapeutic use. Drugs 1987; 34: 350–71

    Article  PubMed  CAS  Google Scholar 

  3. Coombs RRA, Gell PGH. Classification of allergic reactions responsible for clinical hypersensitivity and disease. In: Gell PGH, Coombs RRA, Lachmann PJ, editors. Clinical Aspects of Immunology. 3rd ed. Oxford: Blackwell Scientific, 1975: 761–81

    Google Scholar 

  4. De Leeuw I, Delvigne C, Bekaert J. Insulin allergy treated with human insulin (recombinant DNA). Diabetes Care 1982; 5Suppl. 2: 168–70

    PubMed  Google Scholar 

  5. Bruni B, Barolo P, Blatto A, et al. Treatment of allergy to heterologous monocomponent insulin with human semisynthetic insulin. Diabetes Care 1988; 5: 59–62

    Article  Google Scholar 

  6. Colagiuri S, Dellit L. Suspected allergy to insulin preparations [letter]. Diabetes Care 1988; 11: 365–6

    PubMed  CAS  Google Scholar 

  7. Plantin P, Sassolas B, Guillet MH, et al. Accidents cutanes allergiques aux insulins. Ann Dermatol Venereol 1988; 115: 813–7

    PubMed  CAS  Google Scholar 

  8. Kim R. Anaphylaxis to protamine masquerading as an insulin allergy. Del Med J 1993; 65: 17–23

    PubMed  CAS  Google Scholar 

  9. Chenon D, Fabro M, Richard JL, et al. Allergie à une insuline humaine biogenetique protamine, avec une augmentation importante des taux anticorps anti-insuline et d’eosinophiles. Presse Med 1989; 18: 1297–8

    PubMed  CAS  Google Scholar 

  10. Gossain VV, Rovner DR, Mohan K. Systemic allergy to human (recombinant DNA) insulin. Ann Allergy 1985; 55: 116–8

    PubMed  CAS  Google Scholar 

  11. Zubeldia JM, Arrieta FJ, Saavedra P, et al. Alergia a la insulina humana aspectos clinicos e inmunologicos y actitud terapeutica: a proposito de un caso. Rev Clin Esp 1988; 183: 193–6

    PubMed  CAS  Google Scholar 

  12. Small P, Lerman S. Human insulin allergy. Ann Allergy 1984; 53: 39–41

    PubMed  CAS  Google Scholar 

  13. García-Ortega P, Knobel H, Mirada A. Sensitisation to human insulin [letter]. BMJ 1984; 288: 1271

    Article  PubMed  Google Scholar 

  14. Mirza IH, Wilkin TJ. Antibody specificity in the immune response to insulin. Int Arch Allergy Appl Immunol 1989; 89: 261–3

    Article  PubMed  CAS  Google Scholar 

  15. Balsells MC, Corcoy RM, Lleonart RB, et al. Primary allergy to human insulin in patient with gestational diabetes [letter]. Diabetes Care 1991; 14: 423–4

    PubMed  CAS  Google Scholar 

  16. Nagel C, Talunlicar M, Humbert I, et al. Allergie gegen human-insulin. Dtsch Med Wochenschr 1988; 113: 1013–6

    Article  PubMed  CAS  Google Scholar 

  17. Grammer LC, Roberts M, Buchanan TA, et al. Specificity of immunoglobulin E and immunoglobulin G against human (recombinant DNA) insulin in human insulin allergy and resistance. J Lab Clin Med 1987; 109: 141–6

    PubMed  CAS  Google Scholar 

  18. Ross J. Allergy to insulin Pediatr Clin North Am 1984; 31: 675–87

    PubMed  CAS  Google Scholar 

  19. Reeves WG, Allen BR, Tattersall RB. Insulin induced lipoatrophy: Evidence for an immune pathogenesis. BMJ 1980; 280: 1500–3

    Article  PubMed  CAS  Google Scholar 

  20. Soto-Aguilar MC, de Shazo RD, Morgan JE, et al. IgG subclass response to insulin in patients with immunologic insulin resistence [abstract]. J Allergy Clin Immunol 1989; 83: 269

    Google Scholar 

  21. Ganz MA, Unterman T, Roberts M, et al. Resistance and allergy to recombinant human insulin. J Allergy Clin Immunol 1990; 86: 45–52

    Article  PubMed  CAS  Google Scholar 

  22. Reynolds JEF. Martindale: the extra pharmacopoeia. 29th ed. London: The Pharmaceutical Press, 1989

    Google Scholar 

  23. Weiss ME, Nyhan D, Zhikang P, et al. Association of protamine IgE and IgG antibodies with life-threatening reactions to intravenous protamine. N Engl J Med 1989; 320: 886–92

    Article  PubMed  CAS  Google Scholar 

  24. Levy JH, Schwieger IM, Zaidan JR, et al. Evaluation of patients at risk for protamine reactions. J Thorac Cardiovasc Surg 1989; 98: 200–4

    PubMed  CAS  Google Scholar 

  25. Gin H, Aubertin J. Generalized allergy due to zinc and protamine in insulin preparation treated with insulin pump [letter]. Diabetes Care 1987; 10: 789–90

    PubMed  CAS  Google Scholar 

  26. Van Arsdel PP, Larson EB. Diagnostic tests for patients with suspected allergic disease. Ann Intern Med 1989; 110: 304–12

    Google Scholar 

  27. American College of Physicians. Allergy testing: position paper. Ann Intern Med 1989; 110: 317–20

    Google Scholar 

  28. AAAI Board of Directors. Allergen skin testing: position statement. J Allergy Clin Immunol 1993; 92: 636–7

    Google Scholar 

  29. Arkins JA, Engbring NH, Lennon EJ, et al. The incidence of skin reactivity to insulin in diabetic patients. J Allergy 1962; 33: 69–72

    Article  PubMed  CAS  Google Scholar 

  30. Lieberman P, Patterson R, Metz R, et al. Allergic reactions to insulin. JAMA 1971; 215: 1106–12

    Article  PubMed  CAS  Google Scholar 

  31. Marcos C, Cuesta J, Cuevas M, et al. Specific IgE antibody response to human insulin in diabetic subject. Allergol Immunopathol (Madr) 1993; 21: 141–4

    CAS  Google Scholar 

  32. Würzburger MI, Prelevic GM, Despotovic N. Delayed-type allergy against various insulin preparations including human semisynthetic insulin. Ann Allergy 1987; 59: 44–7

    PubMed  Google Scholar 

  33. Weiss ME, Chatham F, Kagey-Sobotka A, et al. Serial immunological investigations in a patient who had a life-threatening reaction to intravenous protamine. Clin Exp Allergy 1990; 20: 713–20

    Article  PubMed  CAS  Google Scholar 

  34. Child DF, Johansson SGO. IgE antibody studies in a case of generalized allergic reaction to human insulin. Allergy 1984; 39: 630–3

    Article  PubMed  CAS  Google Scholar 

  35. Fireman P, Fineberg SE, Galloway JA. Development of IgE antibodies to human (recombinant DNA), porcine, and bovine insulins in diabetic subjects. Diabetes Care 1982; 5Suppl. 2: 119–25

    PubMed  Google Scholar 

  36. Petersen KG, Khalaf A, Naithani V, et al. IgE antibodies to insulin and related peptides, a result of insulin treatment? Diabetes Res Clin Pract 1987; 7: 41–6

    Article  Google Scholar 

  37. Keilacker H, Rjasanowski I, Woltanski KP, et al. Different insulin antibody formation in diabetic patients treated with crystallized or highly purified insulins is a transient phenomenon. Horm Metab Res 1989; 21: 398–9

    Article  PubMed  CAS  Google Scholar 

  38. Grammer LC, Patterson R. Proteins: chymopapain and insulin. J Allergy Clin Immunol 1984; 74: 635–40

    Article  PubMed  CAS  Google Scholar 

  39. Grammer L, Chen P, Patterson R. Evaluation and management of insulin allergy. J Allergy Clin Immunol 1983; 71: 250

    Article  PubMed  CAS  Google Scholar 

  40. Lleonart R, Balsells M, Corcoy R, et al. Primary hypersensitivity to human insulin [abstract]. Clin Exp Allergy 1990; 20Suppl. 1: 208 A

    Google Scholar 

  41. Bachmann W, Hasche H, Nehnert H, et al. Intradermal desensitisation with human insulin (recombinant DNA) in a patient with severe allergic skin reaction due to insulin. Diabetes Care 1982; 5Suppl. 2: 165–7

    PubMed  Google Scholar 

  42. Loeb JA, Herold KC, Barton KP, et al. Systematic approach to diagnosis and management of biphasic insulin allergy with local anti-inflammatory agents. Diabetes Care 1989; 12: 421–3

    Article  PubMed  CAS  Google Scholar 

  43. Haldoway IM, Wilson JD. Cutaneous insulin allergy responsive to oral desensitisation and aspirin. BMJ 1984; 289: 1565–6

    Article  Google Scholar 

  44. Spijker AJ, Poortman J, Thijssen JHH, et al. Decrease of circulating insulin antibodies in two patients treated with continuous subcutaneous infusion of human insulin (recombinant DNA). Diabetes Care 1989; 5Suppl. 2: 171–4

    Google Scholar 

  45. Valentini V, Cimino A, Rocca L, et al. CSII in management of insulin allergy [letter]. Diabetes Care 1988; 11: 97–8

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Allergy Unit, Servei d’Al.lèrgia, Hospital General de Manresa, La Culla s/n, 08240, Manresa, Barcelona, Spain

    Ramon Lleonart Bellfill

Authors
  1. Ramon Lleonart Bellfill
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bellfill, R.L. Insulin Allergy. Clin Immunother 2, 7–12 (1994). https://doi.org/10.1007/BF03258517

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03258517

Keywords

Search

Navigation