Case Study: Immunogenicity of Insulin

  • Henriette Mersebach
  • Fannie Smith
  • Thomas Sparre
  • Lisbeth Bjerring Jensen
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume VIII)


Gestational Diabetes Mellitus Human Insulin Insulin Glargine Insulin Aspart Insulin Lispro 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agu, R. U., Ugwoke, M. I., Armand, M., Kignet, R., and Verbaeke, N. 2001. The lung as a route for systemic delivery of therapeutic proteins and peptides. Respir. Res. 2:198–209.PubMedCrossRefGoogle Scholar
  2. Bartley, P. C., Bogoev, M., Larsen, J., and Philotheou, A. 2007. Long-term efficacy and safety of insulin detemir versus NPH insulin in subjects with type 1 diabetes using a treat-to-target basal-bolus regimen with insulin aspart at meals: A 2-year, randomized, controlled trial. Diabetic Medicine (in press).Google Scholar
  3. Bolli, G., de Feo, P., Compagnucci, P., Cartechini, M. G., Angeletti, G., Santeusanio, F., Brunetti, P., and Gerich, J. E. 1983. Abnormal glucose counterregulation in insulin-dependent diabetes mellitus. Interaction of anti-insulin antibodies and impaired glucagon and epinephrine secretion. Diabetes 32:134–141.PubMedCrossRefGoogle Scholar
  4. Bolli, G. B., Dimitriadis, G. D., Pehling, G. B., Baker, B. A., Haymond, M. W., Cryer, P. E., and Gerich, J. E. 1984. Abnormal glucose counterregulation after subcutaneous insulin in insulin-dependent diabetes mellitus. N. Engl. J. Med. 310:1706–1711.PubMedCrossRefGoogle Scholar
  5. Ceglia, L., Lau, J., and Pittas, A. G. 2006. Meta-analysis: efficacy and safety of inhaled insulin therapy in adults with diabetes mellitus. Ann. Intern. Med. 145:665–675.PubMedGoogle Scholar
  6. The Diabetes Control and Complications Trial Research Group. 1993. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Eng. J. Med. 329:977–986.CrossRefGoogle Scholar
  7. D’Armiento, M., Salabé, H., Vetrano, G., Scucchia, M., and Pachi, A. 1980. Decrease of thyroid antibodies during pregnancy. J. Endocrin. Invest. 3:437–438.Google Scholar
  8. Exon, P. D., Dixon, K., and Malins, J. M. 1974. Insulin antibodies in diabetic pregnancy. Lancet 2 (7873):126–128.PubMedCrossRefGoogle Scholar
  9. Fabbri L. 2006. Pulmonary safety of inhaled insulins: a review of the current data. Curr. Med. Res. Opin. 22 (Suppl 3):21–28.CrossRefGoogle Scholar
  10. Fineberg, N. S., Fineberg, S. E., Anderson, J. H., Birkett, M. A., Gibson, R. G., and Hufferd, S. 1996. Immunologic effects of insulin lispro (Lys (B28), Pro (B29) human insulin) in IDDM and NIDDM patients previously treated with insulin. Diabetes 45:1750–1754.PubMedCrossRefGoogle Scholar
  11. Fineberg, S. E., Huang, J., Brunelle, R., Gulliya, K. S., and Anderson, J. H. 2003. Effect of long-term exposure to insulin lispro on the induction of antibody response in patients with type 1 or type 2 diabetes. Diabetes Care 26:89–96.PubMedCrossRefGoogle Scholar
  12. Fineberg, S. E., Kawabata, T., Finco-Kent, D., Liu, C., and Krasner, A. 2005. Antibody response to inhaled insulin in patients with type 1 or type 2 diabetes. An analysis of initial phase II and III inhaled insulin (Exubera) trials and a two-year extension trial. J. Clin. Endocrinol. Metab. 90:3287–3294.PubMedCrossRefGoogle Scholar
  13. Garg, S., Rosenstock, J., Silverman, B. L., Sun, B., Konkoy, C. S., de la Pena, A., and Muchmore, D. B. 2006. Efficacy and safety of preprandial human insulin inhalation powder versus injectable insulin in patients with type 1 diabetes. Diabetologia 49:891–899.PubMedCrossRefGoogle Scholar
  14. Gönsslen, M. 1925. Über inhalation von insulin. Klin. Wochenschr. 4 (Jahrgang 2):71.CrossRefGoogle Scholar
  15. Hamalainen, A. M., Ronkainen, M. S., Akerblom, H. K., and Knip, M. 2000. Postnatal elimination of transplacentally acquired disease-associated antibodies in infants born to families with type 1 diabetes. The Finnish TRIGR Study group Trial to reduce IDDM in the genetically at risk. J. Clin. Endocrionol. Metab. 85: 4249–4253.CrossRefGoogle Scholar
  16. Heise, T., Bott, S., Tusek, C., Stephan, J.-A., Kawabata, T., Finco-Kent, D., Liu, C., and Krasner, A. 2005. The effect of insulin antibodies on the metabolic action of inhaled and subcutaneous insulin: a prospective randomized pharmacodynamic study. Diabetes Care 28:2161–2169.PubMedCrossRefGoogle Scholar
  17. Heding, L. G., Marshall, M. O., Persson, B., Dahlquist, G., Thalme, B., Lindgren, F., Åkerblom, H. K., Rilva, A., Knip, M., Ludvigsson, J., Stenhammar, L., Strömberg, L., Søvik, O., Bævre, H., Wefring, K., Vidnes, J., Kjærgård, J. J., Bro, P., and Kaad, P. H. 1984. Immunogenicity of monocomponent human and porcine insulin in newly diagnosed Type 1 (insulin-dependent) diabetic children. Diabetologia 27:96–98.PubMedCrossRefGoogle Scholar
  18. Hermansen, K., Rönnemaa, T., Petersen, A. H., Bellaire, S., and Adamson, U. 2004. Intensive therapy with inhaled insulin via the AERx insulin diabetes management system: a 12-week proof-of-concept trial in patients with type 2 diabetes. Diabetes Care 27:162–167.PubMedCrossRefGoogle Scholar
  19. Heubner, W., De Jongh, S. E., and Laquer, E. 1924. Über inhalation von insulin. Klin. Wochenschr. 3 (Jahrgang 51):2342–2343.Google Scholar
  20. Holmberg, H., Mersebach, H., Kanc Hanzel, K., and Ludvigsson, J. 2007. Antibody response to insulin in children and adolescents with newly diagnosed type 1 diabetes. Diabetes 56 (Suppl 1):A476 (submitted for publication).Google Scholar
  21. Jovanovic, L., Ilic, S., Pettitt, D. J., Hugo, K., Gutierrez, M., Bowsher, R. R., and Bastyr, E.J. 1999. Metabolic and immunologic effects of insulin lispro in gestational diabetes. Diabetes Care 22:1422–1427.PubMedCrossRefGoogle Scholar
  22. Jovanovic, L., Howard, C., Pettitt, D., Zisser, H., and Ospina P. 2005. Insulin aspart vs. regular human insulin in basal/bolus therapy for patients with gestational diabetes mellitus: safety and efficacy. Diabetologia 48 (Suppl 1):A317.Google Scholar
  23. Lapolla, A., Dalfra, M. G., and Fedele, D. 2005. Insulin therapy in pregnancy complicated by diabetes: are insulin analogs a new tool? Diabetes Metab. Res. Rev. 21:241–52.PubMedCrossRefGoogle Scholar
  24. Lindholm, A., Jensen, L. B., Home, P. D., Raskin, P., Boehm, B. O., and Rastam, J. 2002. Immune responses to insulin aspart and biphasic insulin aspart in people with type 1 and type 2 diabetes. Diabetes Care 25:876–882.PubMedCrossRefGoogle Scholar
  25. Lindsay, R. S., Ziegler, A. G., Hamilton, B. A., Calder, A. A., Johnstone, F. D., and Walker, J. D. 2004. Type 1 diabetes-related antibodies in the fetal circulation: Prevalence and influence on cord insulin and birth weight in offspring of mothers with type 1 diabetes. J. Clin. Endocrinol. Metab. 89:3436–3439.PubMedCrossRefGoogle Scholar
  26. Marshall, M. O., Heding, L. G., Villumsen, J., Aakerblom, H. K., Baevre, H., Dahlquist, G., Kjaergaard, J. J., Knip, M., Lindgren, F., Ludvigsson, J., Persson, B., Stenhammar, L., Stromberg, L., Sovik, O., Thalme, B., Vidnes, J., and Wefring, K. 1988. Development of insulin antibodies, metabolic control and beta cell function in newly diagnosed insulin dependent diabetic children treated with monocomponent human insulin or monocomponent porcine insulin. Diabetes Res. 9:169–175.PubMedGoogle Scholar
  27. Mathiesen, E., Kinsley, B., McCance, D., Duran, S., Heller, S., Bellaire, S., and Raben, A. 2007. Maternal Hypoglycemia and Glycemic Control in Pregnancy: A Randomized Trial Comparing Insulin Aspart with Human Insulin in 322 Subjects with Type 1 Diabetes. Diabetes Care 30:771–776.PubMedCrossRefGoogle Scholar
  28. McCance, D., Damm, P., Mathiesen, E., Kaaja, R., Dunne, F., Hod, M., Jensen, L.E., and Mersebach, H. 2007. No increase in insulin antibodies during pregnancy and no clear evidence of transfer of insulin aspart across the placenta in pregnant women with type 1 diabetes. Diabetes 56 (Suppl 1):A22 (submitted for publication).Google Scholar
  29. Menon, R. K., Cohen, R. M., Sperling, M. A., Cutfield, W. S., Mimouni, F., and Khoury, J. C. 1990. Transplacental passage of insulin in pregnant women with insulin-dependent diabetes mellitus. Its role in fetal macrosomia. N. Engl. J. Med. 323:309–315.PubMedCrossRefGoogle Scholar
  30. Moses, R., Lunt, H., Bartley, P., O’Brien, R., Clauson, P., Vesterager, A., Wollmer, P., and Roberts, A. 2006. Periprandial inhaled human insulin via the AERx insulin Diabetes Management System (iDMS) vs. subcutaneous insulin aspart in type 1 diabetes. Diabetic Med. 23 (Suppl 4):338.Google Scholar
  31. Roberts, A., Wilson, D., McElduff, A., Prins, J., Simpson, R., Haahr, H., Raastam, J., and Moses, R. 2006. Pharmacokinetics of inhaled human insulin via the AERx™ insulin Diabetes Management System (iDMS) in subjects with type 1 diabetes, naïve and non-naïve to inhaled insulin. Diabetic Med. 23 (Suppl 4):343.Google Scholar
  32. Schernthaner, G. 1993. Immunogenicity and allergenic potential of animal and human insulins. Diabetes Care 16:155–165.PubMedGoogle Scholar
  33. Spellacy, W. N., and Goetz, F. C. 1963. Insulin antibodies in pregnancy. Lancet 2:222–224.PubMedCrossRefGoogle Scholar
  34. Teeter, J. G., and Riese, R. J. 2006. Dissociation of lung function changes with humoral immunity during inhaled human insulin therapy. Am. J. Respir. Crit. Care Med. 173:1194–2000.PubMedCrossRefGoogle Scholar
  35. UKPDS Group. 1998. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853.CrossRefGoogle Scholar
  36. Quattrin, T., Berlanger, A., Bohannon, N. J., Schwartz, S. L., and Exubera Phase III Study Group. 2004. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 1 diabetes: results of a 6-month, randomized, comparative trial. Diabetes Care 27:2622–2627.PubMedCrossRefGoogle Scholar
  37. Velcovsky, H. G., and Federlin, K. F. 1982. Insulin-specific IgG and IgE antibody response in type 1 diabetes subjects exclusively treated with human insulin (recombinant DNA). Diabetes Care 5 (Suppl 2):126–128.PubMedGoogle Scholar
  38. Weiss, P. A., Kainer, F., and Haas J. 1998. Cord blood insulin to assess the quality of treatment in diabetic pregnancies. Early Hum. Dev. 51:187–195.PubMedCrossRefGoogle Scholar
  39. Wollmer, P., Peiber, T. R., Gall, M.-A., and Brunton, S. 2007. Delivering Needle-Free Insulin using AERxiDMS (Insulin Diabetes Management System) Technology. Diabetes Technol. & Ther. 9 (Suppl 1):S57–64.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2008

Authors and Affiliations

  • Henriette Mersebach
  • Fannie Smith
  • Thomas Sparre
  • Lisbeth Bjerring Jensen

There are no affiliations available

Personalised recommendations