Since no recombinant canine insulin is available, use of bovine or porcine insulin to treat diabetic dogs is common because the B chains of canine, bovine, and porcine insulin are identical. However,whereas canine and porcine A chains have identical amino acid sequences, canine and bovine insulins differ at positions 8 and 10. Therefore, porcine insulin can be considered a self-antigen in dogs,whereas bovine insulin is a heterologous protein. A prospective observational study was conducted in diabetic dogs to determine whether treatment with heterologous insulin is more likely to stimulate production of antiinsulin antibodies (AIA) than is treatment with homologous insulin. The objectives were to determine the prevalence of insulin autoantibodies in untreated dogs, test the hypothesis that heterologous insulin is more immunogenic than homologous insulin, and determine the subunit specificity and isotype of AIA in insulin-treated dogs.Test groups were 1) diabetic dogs sampled before insulin therapy; 2) diabetic dogs sampled after treatment with porcine (homologous) insulin, bovine (heterologous) lente insulin, or bovine protamine zinc insulin; and 3) nondiabetic control dogs. Sera were analyzed 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 antiinsulin IgG1:IgG2 ratios. CDV and TG reactivity did not differ among the groups.There was no significant difference in AIA between control and porcine insulin–treated diabetic dogs.A small proportion of dogs demonstrated AIA before diagnosis, consistent with an autoimmune response. Antibody development after treatment was most predominant in dogs treated with (heterologous) bovine insulin preparations, but not all diabetic dogs treated with bovine insulin developed AIA.

COMMENTARY: Because of the numerous changes in insulin availability, many veterinarians have questions about suitability of human insulin preparations in treating diabetic dogs and cats or use of animal-derived insulins that have different amino acid (AA) sequences than the species for which they are intended to be used.This welldesigned study examined 40 dogs sampled before insulin treatment,100 dogs treated with porcine insulin, 100 dogs treated with bovine lente insulin, 20 dogs treated with a bovine protamine zinc insulin, and 120 nondiabetic control dogs.AIA was detected in 5 of 40 newly diagnosed dogs before insulin therapy, did not differ between control dogs and dogs treated with porcine insulin, and its levels were higher in dogs treated with both bovine insulin products.Although this finding indicates that bovine insulin is more immunogenic than porcine insulin in diabetic dogs, the role of AIA in insulin resistance or poor glycemic control is unknown.Because bovine insulins are not commercially available in the United States (as they are in Europe), AIA formation as a result of bovine insulin use probably will not present a clinical problem for our patients. It would be interesting to see a similar well-designed study examining the prevalence and clinical significance of AIA in canine patients treated with human-derived insulin preparations.—David Bruyette, DVM,MS, Diplomate ACVIM

Anti-insulin antibodies in diabetic dogs before and after treatment with different insulin preparations. Davison LJ,Walding B,Herrtage ME, Catchpole B. J VET INTERN MED 22:1317-1325, 2008.