Background: Canine diabetes mellitus (DM) is a common endocrinopathy with an unclear etiology. For a better understanding of the underlying mechanisms, there is a need for comprehensive epidemiologic studies. Earlier studies have shown that the risk of disease is higher in certain dog breeds.Hypothesis: Incidence, age of onset, survival and sex proportion of DM vary by breed. Animals: Data from a cohort of 182,087 insured dogs aged 5-12 years accounting for 652,898 dog-years at risk were studied retrospectively.Methods: Incidence rates by sex, breed, and geography were calculated with exact denominators. Age-specific incidence and survival after 1st DM claim were computed with Cox's regression and Kaplan-Meier survival function. Multivariable survival analysis was performed for the outcome diagnosis of DM with age, sex, and geography tested as fixed effects, previous endocrine or pancreatic diseases tested as time-dependent covariates, and breed tested as a random effect.Results: The mean age at 1st insurance claim for the 860 DM dogs (72% females) was 8.6 years. The incidence of DM was 13 cases per 10,000 dog-years at risk. Australian Terriers, Samoyeds, Swedish Elkhounds, and Swedish Lapphunds were found to have the highest incidence. The proportion of females with DM varied significantly among breeds. Swedish Elkhounds, Beagles, Norwegian Elkhounds, and Border Collies that developed DM were almost exclusively females. The multivariable model showed that breed, previous hyperadrenocorticism, and female sex were risk factors for developing DM. Median survival time was 57 days after 1st claim. Excluding the 223 dogs that died within 1 day, the median survival time was 2 years after 1st claim of DM.Conclusion: The significant breed-specific sex and age differences shown in this study indicate that genetic variation could make breeds more or less susceptible to different types of DM.

The unique canine breed structure makes dogs an excellent model for studying genetic diseases. Within a dog breed, linkage disequilibrium is extensive, enabling genome-wide association (GWA) with only around 15,000 SNPs and fewer individuals than in human studies. Incidences of specific diseases are elevated in different breeds, indicating that a few genetic risk factors might have accumulated through drift or selective breeding. In this study, a GWA study with 81 affected dogs (cases) and 57 controls from the Nova Scotia duck tolling retriever breed identified five loci associated with a canine systemic lupus erythematosus (SLE)-related disease complex that includes both antinuclear antibody (ANA)-positive immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). Fine mapping with twice as many dogs validated these loci. Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases.

Background: Female Elkhounds are shown to be at increased risk for diabetes mellitus, and occurrence of diabetes during pregnancy has been described in several cases.Hypothesis: Onset of diabetes mellitus in Elkhounds is associated with diestrus. Animals: Sixty-three Elkhounds with diabetes mellitus and 26 healthy controls. Methods: Medical records from 63 Elkhounds with diabetes were reviewed and owners were contacted for follow-up information. Blood samples from the day of diagnosis were available for 26 dogs. Glucose, fructosamine, C-peptide, growth hormone (GH), insulin-like growth factor-1, progesterone, and glutamate decarboxylase isoform 65-autoantibodies were analyzed and compared with 26 healthy dogs. Logistic models were used to evaluate the association of clinical variables with the probability of diabetes and with permanent diabetes mellitus after ovariohysterectomy (OHE).Results: All dogs in the study were intact females and 7 dogs (11%) were pregnant at diagnosis. The 1st clinical signs of diabetes mellitus occurred at a median of 30 days (interquartile range [IQR], 3-45) after estrus, and diagnosis was made at a median of 46 days (IQR, 27-62) after estrus. Diabetes was associated with higher concentrations of GH and lower concentrations of progesterone compared with controls matched for time after estrus. Forty-six percent of dogs that underwent OHE recovered from diabetes with a lower probability of remission in dogs with higher glucose concentrations (odds ratio [OR], 1.2; P 5 .03) at diagnosis and longer time (weeks) from diagnosis to surgery (OR, 1.5; P 5 .05).Conclusions: Diabetes mellitus in Elkhounds develops mainly during diestrus and pregnancy. Immediate OHE improves the prognosis for remission of diabetes.

Aims/HypothesisDiabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.MethodsSera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.ResultsNone of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.Conclusions/InterpretationsContrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.

BackgroundDiabetes mellitus (DM) is a common endocrinopathy in cats. Most affected cats suffer from a type of diabetes similar to type 2 diabetes in humans. An increasing prevalence has been described in cats, as in humans, related to obesity and other lifestyle factors.ObjectivesTo describe the incidence of DM in insured Swedish cats and the association of DM with demographic risk factors, such as age, breed and sex.AnimalsA cohort of 504,688 individual cats accounting for 1,229,699 cat‐years at risk (CYAR) insured by a Swedish insurance company from 2009 to 2013.MethodsWe used reimbursed insurance claims for the diagnosis of DM. Overall incidence rates and incidence rates stratified on year, age, breed, and sex were estimated.ResultsThe overall incidence rate of DM in the cohort was 11.6 cases (95% confidence interval [CI], 11.0–12.2) per 10,000 CYAR. Male cats had twice as high incidence rate (15.4; 95% CI, 14.4–16.4) as females (7.6; 95% CI, 6.9–8.3). Domestic cats were at higher risk compared to purebred cats. A significant association with breed was seen, with the Burmese, Russian Blue, Norwegian Forest cat, and Abyssinian breeds at a higher risk compared to other cats. No sex predisposition was found among Burmese cats. Several breeds with a lower risk of DM were identified.Conclusions and clinical importanceOur results verify that the Burmese breed is at increased risk of developing DM. We also identified several previously unreported breeds with increased or decreased risk of DM.

Nova Scotia duck tolling retrievers are predisposed to a SLE-related disease complex including immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). IMRD involves symptoms that resemble those seen in systemic autoimmune rheumatic diseases, such as systemic lupus erythematosus, SLE, or SLE-related diseases, in humans. This disease complex involves persistent lameness, stiffness, mainly after resting, and palpable pain from several joints of extremities. The majority of affected dogs display antinuclear autoantibody (ANA)-reactivity. SRMA is manifested in young dogs with high fever and neck stiffness and can be treated with corticosteroids. We have investigated the possible role of MHC class II as a genetic risk factor in IMRD and SRMA etiology. We performed sequence-based typing of the DLA-DRB1, -DQA1, and -DQB1 class II loci in a total of 176 dogs including 51 IMRD (33 ANA-positive), 49 SRMA cases, and 78 healthy controls (two dogs were both IMRD- and SRMA-affected). Homozygosity for the risk haplotype DRB1*00601/DQA1*005011/DQB1*02001 increased the risk for IMRD (OR = 4.9; ANA-positive IMRD: OR = 7.2) compared with all other genotypes. There was a general heterozygote advantage, homozygotes had OR = 4.4 (ANA-positive IMRD: OR = 8.9) compared with all heterozygotes. The risk haplotype contains the five amino acid epitope RARAA, known as the shared epitope for rheumatoid arthritis. No association was observed for SRMA. We conclude that DLA class II is a highly significant genetic risk factor for ANA-positive IMRD. The results indicate narrow diversity of DLA II haplotypes and identify an IMRD-related risk haplotype, which becomes highly significant in homozygous dogs.

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The aim of this study was to explore the development of the gut microbiota in 168 German Shepherd dogs (30 litters) from 7 weeks to 18 months of age and furthermore, to study the effect of relatedness, maternal microbiota composition and living environment in a large and well-defined population of dogs. Using 454 pyrosequencing, we assessed the effects of pre- and postnatal probiotic supplementation (Lactobacillus johnsonii NCC533 (La1)) and analysed whether administration of the probiotic strain influenced fecal microbiota composition in a placebo controlled double-blinded study. The bitches were treated with probiotics or placebo during last trimester of pregnancy and until their puppies were 8 weeks old, the puppies received the same treatment as their mothers between 3–12 weeks of age. Samples from bitches were collected at pregnancy day 42, partum, 4 weeks postpartum and 7 weeks postpartum and from puppies at the age 4 weeks, 7 weeks, 12–13 months and 15–18 months. Serum IgA, total serum IgE, fecal IgA and IgG antibody responses against canine distemper virus were analysed by ELISA in order to detect any immune stimulating effects of the probiotic strain. Analysis of the fecal microbiota composition showed that the predominant phyla were the same in 7 weeks old puppies as in pregnant and lactating bitches (Firmicutes, Fusobacteria, Bacteroidetes). Proportions among different bacteria as well as diversity varied from 7 weeks old puppies up to 15–18 months of age. Litter mates had a more similar fecal microbiota compared to unrelated dogs and 7 weeks old puppies were more similar to their mothers than to unrelated bitches at 7 weeks postpartum but not at partum. We observed a change in the relative abundance of different bacteria during lactation, and an increase in diversity from pregnancy to end of lactation. The microbial diversity was affected by living area where dogs living in big cities had higher diversity compared to dogs living at the countryside. However, we were not able to demonstrate an effect by pre and postnatal exposure to Lactobacillus johnsonii NCC533 (La1) upon the diversity or composition of the microbiota or the levels of serum IgA, total serum IgE, fecal IgA or vaccine response. Our findings provide a better understanding of the canine fecal microbiota in growing dogs as well as in pregnant and lactating bitches. This information forms a basis for further research on the connection between early gut colonization and immune function later in life.