Incidence of Diabetes Mellitus in Insured Swedish Cats in Relation to Age, Breed and Sex

Background: Diabetes 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. Objectives: To describe the incidence of DM in insured Swedish cats and the association of DM with demographic risk factors, such as age, breed and sex. Animals: A 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. Methods: We used reimbursed insurance claims for the diagnosis of DM. Overall incidence rates and incidence rates stratified on year, age, breed, and sex were estimated. Results: The 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 importance: Our 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

Disease patterns and incidence of immune-mediated disease in insured Swedish Nova Scotia Duck Tolling Retrievers

In this study, morbidity in insured Nova Scotia Duck Tolling Retriever (NSDTR) dogs from Sweden was investigated and compared with all other breeds and other retriever breeds. In addition to describing common morbidities in NSDTRs, the hypotheses that NSDTRs are predisposed to lymphoma, immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA) were tested. Included in the study were 445,336 dogs; of which, 2890 were NSDTRs that had been covered by veterinary insurance from the Agria Insurance Company (Stockholm, Sweden) at some point during the years 1995-2006. Incidences of various health problems were calculated using the number of veterinary visits as the numerator and the exact time at risk as the denominator. Overall, morbidity was higher in NSDTRs compared with all other breeds, but similar compared with other retriever breeds. The most common causes of veterinary visits in NSDTRs were injuries, gastrointestinal disease and locomotor disorders, with NSDTRs at increased risk of these compared with all other breeds. The incidences for IMRD, SRMA and lymphoma were significantly higher in NSDTRs than in all other dog breeds and all other retriever breeds. The study describes morbidity in NSDTRs, and identifies several disorders to which the breed is predisposed

Investigation of interference from canine anti-mouse antibodies in hormone immunoassays

Background: Canine anti-mouse antibodies are a potential source of immunoassay interference, but erroneous immunoassay results are not always easily identifiable. Anti-Mullerian hormone (AMH) is a marker for the presence of gonads in dogs, but elevated AMH concentrations in neutered dogs could also be caused by antibody interference. For other assays, a discrepant result obtained after antibody precipitation might indicate antibody interference. Objectives: We aimed to evaluate if canine anti-mouse antibodies are a source of erroneous results in the AMH assay and if antibody precipitation with polyethylene glycol (PEG) is a useful tool for detecting antibody interference in a variety of immunoassays used in the veterinary clinical laboratory. Methods: Twenty-nine positive and 25 negative samples for anti-mouse antibodies were analyzed for AMH, canine total thyroxine (TT4), canine thyroid-stimulating hormone (TSH) and progesterone before and after treatment with PEG. Results that differed by more than four SDs from the intra-assay coefficients of variation were considered discrepant. Elevated AMH concentrations in neutered dogs with anti-mouse antibodies and no visible gonads present were considered evidence of interference. Results: Evidence of antibody interference was found in two samples analyzed for AMH. The presence of anti-mouse antibodies did not lead to a higher proportion of discrepant results after PEG treatment for any of the immunoassays. The overall incidence of discrepant results for healthy controls was very high (73%). Conclusions Canine anti-mouse antibodies are a source of erroneous AMH results. Antibody precipitation with PEG is not a useful tool for detecting interference caused by such antibodies

Antihistone Autoantibodies in Dobermans With Hepatitis

Peer reviewe

Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease

The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H)) and speckled ANA (ANA(S)) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAM-TOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans.Peer reviewe

Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease

The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H)) and speckled ANA (ANA(S)) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAM-TOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans.Peer reviewe

A possible systemic rheumatic disorder in the Nova Scotia duck tolling retriever

Abstract Background A disease complex with chronic musculoskeletal signs, including stiffness and joint pain, and to which there is a strong predisposition in the canine breed Nova Scotia duck tolling retriever (Toller) has been recognized in Sweden. The aim of this first clinical description of the disorder in Tollers was to describe the clinical manifestations and laboratory findings, as well as to try to identify a possible immune-mediated background of the disease and to show the outcome of treatment in 33 Tollers. Methods The study included 33 Tollers with musculoskeletal signs and 20 healthy controls. All the dogs were thoroughly examined and followed for a period of 2 months – 4 years. An IIF-ANA (antinuclear antibody) test and an assay for the presence of antibodies to Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato were performed, as well as some haematology, serum biochemistry and urine tests. Routine radiographic examinations were performed on 11 dogs. Results All the Toller patients showed stiffness and lameness that had lasted for at least 14 days and displayed pain from several joints of extremities on manipulation. Twenty-seven per cent of the dogs also showed muscle pain and 18% different skin symptoms. Seventy per cent of the Tollers with signs of disease displayed a positive IIF-ANA test. Most of the dogs were treated with corticosteroids, with the majority of the dogs (65%) showing good responses. There was no association between the IIF-ANA results and the clinical signs or results of treatment. Conclusion This paper describes a disorder in Nova Scotia duck tolling retrievers where the clinical signs, ANA reactivity and response to corticosteroids strongly suggest that the disorder is immune-mediated. The findings of this research may indicate a chronic systemic rheumatic disorder.</p

Diabetes mellitus in a population of 180,000 insured dogs : incidence, survival, and breed distribution

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 epidermiologic 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 I 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

Characterization of canine anti-mouse antibodies highlights that multiple strategies are needed to combat immunoassay interference

Immunoassays are widely used for detection and quantifcation of analytes in biological samples, but are vulnerable to analytical errors caused by interfering sample substances. Of particular interest are endogenous anti-animal antibodies that may bind to the immunoassay antibodies and cause erroneous test results. This phenomenon is a hazard to patient safety in both human and veterinary medicine. Here, we demonstrate that anti-mouse antibodies in dogs bind selectively to diferent regions of the murine IgG molecule, cross-react with IgG from diferent species, and consist of all major antibody classes present in canine serum (IgA, IgG and IgM). The antibody characteristics varied among individuals and their prevalence difered between two dog breeds. The selective binding to diferent IgG regions suggests that the antibodies might not originate from immunization through exposure to mice or other species. These fndings show that canine anti-mouse antibodies are highly heterogeneous in nature and therefore require a combination of strategies to be counteracted