Lucy Davison, Professor of Veterinary Clinical Genetics and MRC Clinician Scientist Fellow, reflects on the contributions of RVC research to the care of diabetic pets, including several important milestones, and looks to the future.

Vets, nurses and researchers at the RVC have devoted the last 20 years (see timeline below) to improving our understanding of the pathogenesis of canine and feline diabetes mellitus, as well as searching for improvements in the way these conditions are managed.

Diabetes in dogs usually occurs as a result of destruction of insulin-producing pancreatic beta cells, meaning that dogs require insulin injections to survive. In cats, the situation is different, and in some ways is more similar to human type 2 diabetes, where bodyweight and diet play a significant role. Sometimes a change in diet and weight loss is enough to reverse the disease, but many cats still require insulin.

Hypersomatotropism in cats, where the pituitary gland in the brain produces too much growth hormone, can also lead to diabetes. The diagnosis and surgical management of this condition has been pioneered at the RVC.

In addition to clinical and genetics research at the RVC, our understanding of canine and feline diabetes has benefitted from the RVC’s VetCompass project, especially in improving our understanding of risk factors associated with diabetes.

As well as offering medical and surgical expertise in diabetes management at RVC Small Animal Referrals and the Beaumont Sainsbury Animal Hospital, the RVC is now using the latest technologies in genomics to advance healthcare in pets.

Until very recently, genetic analysis of the entire DNA code of an animal (whole genome sequencing) was out of reach for veterinary researchers due to very high costs involved. With the development of new sequencing technologies and ‘big data’ analysis tools, however, things have changed. The whole genome of a patient can now be sequenced for under £1,500. Researchers can identify the smallest variants in dog and cat genomes and determine which of these may be contributing to disease.

The 20-year collection of clinical diabetes samples and data from patients has allowed researchers at the RVC to take advantage of new technologies to answer questions that have been puzzling them for years, such as:

• Why do so many Samoyeds become diabetic?
• Why do we never see diabetes in boxers?
• Why do the breeds which are protected from diabetes sometimes develop pancreatic tumours (insulinoma)?
• Why are Burmese cats more likely to get diabetes than other cats?
• Why are some breeds, such as the Labrador retriever, predisposed to developing diabetes at less than six months of age?

Using funding from a range of sources, including the PetPlan Charitable Trust, the MRC, the ECVIM-CA Clinical Studies Fund, The Samoyed Association, The Burmese Cat Club and BSAVA PetSavers, and with the support of industrial partner Dechra Veterinary Products, RVC researchers are beginning to discover the answers to these genetic questions. More broadly, diabetes research at the RVC has also been supported by a range of sources, including the Beryl Everts and Robert Luff Animal Welfare Trust, the Winn Feline Foundation, The Rumba Foundation, Boehringer Ingelheim, MSD Animal Health, Nestle Purina Pet Care, the Kennel Club Charitable Trust and the Biotechnology Biological Sciences Research Council.

Our diabetes research involves collaborations with researchers internationally, and draws on the clinical and research expertise at the RVC and beyond. The Canine Diabetes Genetics Partnership (caninediabetesgenetics.org), for example, involves participants from a range of institutions, including veterinary clinicians, medical doctors, pathologists, geneticists and bioinformaticians. To date, the Partnership has undertaken whole genome analysis in more than 60 dogs to identify diabetes and insulinoma-related genes.

There is a particular focus on understanding whether diabetes should be managed differently in different breeds, and the next phase of this research will be to determine which genes can be targeted with potential therapies to prevent or treat canine diabetes. The most recent feline diabetes work has also taken advantage of whole genome sequencing to understand which genetic variants are unique to the UK Burmese cat, whether they can explain the increased risk of diabetes in this breed, and whether they offer new targets for treatment.

What does the future hold for the next 20 years of diabetes research?     

Diabetes mellitus is always going to be a very strong and high-impact research theme at the RVC, and we anticipate that not only will we develop new treatments and diagnostic tests, but that ‘wearable tech’, and smartphone Apps, such as the RVC Pet Diabetes App, will transform the care of patients. There is also exciting potential for our genomics work to be translated to other species and to the prevention of other conditions. Already, we are applying our genetics analysis pipelines to breed-associated canine heart disease, lipid disorders and neurological conditions, we are working closely with researchers in human diabetes, and our feline genomics pipeline is being expanded to look at thyroid disease and urinary stone disease, so the future looks very exciting.

As well as leading to new treatments for diabetes management, and maybe even a screening and prevention programme, another potential outcome of our current diabetes genetics research is the integration of genetics into clinical veterinary practice in ‘real time’. In the current world of human ‘precision medicine’, where genetic testing allows personalised therapy for each individual, we hope that it will not be long before precision clinical genomics is a reality at the RVC.

Timeline of RVC contributions to diabetes research and treatment