Anti-insulin antibodies in diabetic dogs before and after treatment with different insulin preparations

J Vet Intern Med. 2008 Nov-Dec;22(6):1317-25. doi: 10.1111/j.1939-1676.2008.0194.x. Epub 2008 Oct 3.


Background: Anti-insulin antibodies (AIA) occur in diabetic dogs after insulin therapy, although their clinical significance is unclear.

Hypothesis: Treatment of diabetic dogs with heterologous insulin is more likely to stimulate production of AIA than is treatment with homologous insulin.

Animals: Diabetic dogs sampled before insulin therapy (n = 40), diabetic dogs sampled following treatment with porcine (homologous) insulin (n = 100), bovine (heterologous) lente insulin (n = 100), or bovine protamine zinc (PZI) insulin (n = 20), and nondiabetic control dogs (n = 120).

Methods: Prospective observational study. Sera were analyzed by ELISA for antibodies against porcine insulin, bovine insulin, insulin A, B, or C peptides, and control antigens; canine distemper virus (CDV) and canine thyroglobulin (TG). Canine isotype-specific antibodies were used to determine total and anti-insulin IgG1 : IgG2 ratios.

Results: There was no difference in CDV or TG reactivity among the groups. AIA were detected in 5 of 40 newly diagnosed (untreated) diabetic dogs. There was no significant difference in AIA (ELISA optical density reactivity) comparing control and porcine insulin-treated diabetic dogs (P > .05). Anti-insulin reactivity was most prevalent in bovine PZI insulin-treated dogs (90%; P < .01), and bovine lente insulin-treated dogs (56%; P < .01). AIA induced by treatment were enriched for the IgG1 isotype.

Conclusions and clinical importance: This study indicates that bovine insulin is more immunogenic than porcine insulin when used for treatment of diabetic dogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology*
  • Cattle
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / veterinary*
  • Dog Diseases / drug therapy*
  • Dog Diseases / immunology
  • Dogs
  • Drug Administration Schedule
  • Female
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / immunology
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / immunology*
  • Insulin / therapeutic use*
  • Male
  • Swine


  • Antibodies
  • Hypoglycemic Agents
  • Insulin