Diabetes Mellitus and Cavalier King Charles Spaniels
The Cavalier King Charles Spaniel is genetically susceptible to developing an incurable disease known as diabetes mellitus, and Cavaliers are at a greater risk of developing diabetes mellitus than many other breeds.
What It Is
Diabetes mellitus is commonly called "sugar diabetes", because it results in excessively high levels of blood sugar, and the presence of sugar (glucose) in the urine. The disease prevents the Cavalier from converting the glucose in its diet into energy. It is caused by a deficiency of the hormone insulin. Insulin is required by muscles, fat tissue, and the liver to utilize carbohydrates, proteins, and fats ingested in the diet.
The average age of dogs that develop diabetes mellitus is 6 to 8 years. However, Cavaliers as young as six months of age have become diabetic and have remained so for the rest of their lives.
In a 2007 study, UK researchers found that the CKCS "showed 8 positive associations for [an IL-10 haplotype which is associated with diabetes], all of which had OR [odds ratio] between 3.30 and 4.05. Such a high number of associated alleles in this gene were indicative of a risk haplotype for this breed. IL-10 did not show any associations for any other breed in this analysis." In a 2009 follow-up study, the same research team found that, "when SNPs were examined for an association with diabetes ... significant associations were observed for ... IL-10 in the Cavalier King Charles Spaniel. These results suggest that canine cytokine genes regulating the TH1/TH2 immune balance might play a contributory role in determining susceptibility to diabetes in [the CKCS]".
Symptoms
Symptoms of the disease include a grossly exaggerated thirst, a poor appetite, weight loss, and a sweet smell on the breath. If the diabetic Cavalier is not treated soon enough and correctly, it can develop far more serious form of diabetes mellitus, called ketoacidosis, with symptoms including sudden onset of cataracts in the eyes, lethargy, vomiting, diarrhea, blindness due to degeneration of the retina, and coma. Ketoacidosis represents a very serious disruption to the dog's metabolism and will most likely result in death if left untreated.
Diagnosis
Diabetes mellitus is diagnosed on the basis of the dog's symptoms and an abnormally high blood glucose measurement. The normal level of glucose in the blood is 4 to 7 mmol/L. Diabetes mellitus is the only common disease which will cause blood glucose levels to rise above and stay above that normal level.
Treatment
Diabetes mellitus cannot be cured, and the Cavalier will require daily, carefully measured and administered injections of insulin for its entire life. The administration of insulin is the most important aspect of controlling diabetes mellitus. Most dogs require only one injection of insulin per day, though two may be needed. Drugs in tablet form which stimulate the pancreas to produce more insulin have proven to be ineffective in controlling diabetes in dogs.
In addition to injecting the insulin daily, the owner of the diabetic Cavalier will need to closely monitor the dog to ensure its diabetes is under control. This may require that the owner collect and test urine samples daily to determine the presence of glucose and adjust the dose of insulin accordingly. Blood glucose monitoring is another way of determining the dosage of insulin.
Breeders' Responsibilities
The Canine Inherited Disorders Database recommends that dogs with symptoms of diabetes mellitus should not be bred, and parents and siblings should be considered potential carriers. As it is considered a likely genetic disease in Cavaliers, all breeding stock should be tested for consistently high blood glucose levels. Any littermates of breeding stock having diabetes mellitus should be taken into consideration. Unfortunately, since the disease is known to not develop until as late as 8 years, breeding stock which may test clear for symptoms of diabetes mellitus may well carry the genes which cause it and may themselves develop symptoms of the disease later in life. Therefore, there is no certain test to assure that any Cavalier breeding stock is clear of diabetes mellitus.
Related Links
Chronic Pancreatitis
Questions for Breeders
Cataracts
Diets
Dogs, Diet,
and Disease: An Owner’s Guide to Diabetes Mellitus, etc.
Veterinary Resources
Control of Canine Genetic Diseases. Padgett, G.A., Howell Book House 1998, pp. 198-199, 232.
Cavalier King Charles Spaniels: An Owner's Companion. John Evans. Crowood Press, 2003, pp. 36, 37.
Guide to Congenital and Heritable Disorders in Dogs. Dodds WJ, Hall S, Inks K, A.V.A.R., Jan 2004, Section II(85).
Dogs, Diet, and Disease: An Owner’s Guide to Diabetes Mellitus, Pancreatitis, Cushing’s Disease, and More. Caroline D. Levin RN. Lantern Publ.2001
Analysis of Candidate Susceptibility Genes in Canine Diabetes. Andrea D. Short, Brian Catchpole, Lorna J. Kennedy, Annette Barnes, Neale Fretwell, Chris Jones, Wendy Thomson, and William E. R. Ollier. J. Heredity; 2007:98(5):518–525. Quote: "This study demonstrates that a number of the candidate genes previously associated with human T1D also appear to be associated with canine diabetes and identifies an IL-10 haplotype which is associated with diabetes in the Cavalier King Charles Spaniel. This suggests that canine diabetes is an excellent comparative and spontaneously occurring disease model of human T1D. ... Of the high-risk alleles, the most striking observation was the number of IL-10 alleles showing association to diabetes in the Cavalier King Charles Spaniel. This breed showed 8 positive associations for this gene, all of which had OR between 3.30 and 4.05. Such a high number of associated alleles in this gene were indicative of a risk haplotype for this breed. IL-10 did not show any associations for any other breed in this analysis. ... In the Cavalier King Charles Spaniel, IL-10 showed a high number of SNPs* to be associated with DM. This is supportive that the gene contributes to disease susceptibility/resistance as the associations are found with more than one SNP. Given the high level of LD that exists across the canine genome, these SNPs are likely to be in strong allelic association and represent haplotypes; such heterogeneity would therefore be better assessed through haplotype analysis. Haplotype analysis in this study identified an associated haplotype in the Cavalier King Charles Spaniel with a v2 of 7.48 (P 5 0.005). This haplotype did not appear to be significant in the other breeds ... " *SNP stands for a "single-nucleotide polymorphism", which is a DNA sequence variation occurring when a single nucleotide in the genome (or other shared sequence) differs between members of a species or between paired chromosomes in an individual.
T cell cytokine gene polymorphisms in canine diabetes mellitus. Short AD, Catchpole B, Kennedy LJ, Barnes A, Lee AC, Jones CA, Fretwell N, Ollier WE. Vet Immunol Immunopathol. 2009 Mar 15;128(1-3):137-46. Quote: "Insulin-deficiency diabetes in dogs shares some similarities with human latent autoimmune diabetes of adults (LADA). Canine diabetes is likely to have a complex pathogenesis with multiple genes contributing to overall susceptibility and/or disease progression. An association has previously been shown between canine diabetes and MHC class II genes, although other genes are also likely to contribute to the genetic risk. Potential diabetes susceptibility genes include immuno-regulatory TH1/TH2 cytokines such as IFNgamma, IL-12, IL-4 and IL-10. We screened these candidate genes for single nucleotide polymorphisms (SNPs) in a range of different dog breeds using dHPLC analysis and DNA sequencing. Thirty-eight of the SNPs were genotyped in crossbreed dogs and seven other breed groups (Labrador Retriever, West Highland White Terrier, Collie, Schnauzer, Cairn Terrier, Samoyed and Cavalier King Charles Spaniel), which demonstrated substantial intra-breed differences in allele frequencies. When SNPs were examined for an association with diabetes by case:control analysis significant associations were observed for IL-4 in three breeds, the Collie, Cairn Terrier and Schnauzer and for IL-10 in the Cavalier King Charles Spaniel. These results suggest that canine cytokine genes regulating the TH1/TH2 immune balance might play a contributory role in determining susceptibility to diabetes in some breeds."
Canine Inherited Disorders Database: http://www.upei.ca/~cidd/Diseases/endocrine%20diseases/diabetes%20mellitus.htm
