People: Lucy Davison, David Brodbelt, Dan O'Neill

Vet Compass Project Type: Dog

Dates: 2018

Background:

In recent decades there has been a dramatic rise in the incidence of Type 1 Diabetes (T1D), particularly in young children (Knip, 2012). This increase is thought to be associated with environmental factors (Åkerblom and Knip, 1998). One hypothesis is that exposure to antibiotics, particularly in the first couple of years of life, influences the development of T1D through alterations to the microbiome and effects on the immune system (Gülden et al., 2015). Rodent models of T1D have shown antibiotic exposure to both increase (Brown et al., 2016) and decrease (Brugman et al., 2006) the risk of developing diabetes. Human studies have shown mixed results between antibiotic exposure in prenatal or early life and development of T1D. Some studies show no association (Tapia et al., 2018), and others an association between multiple prescriptions and an increased risk of T1D (Kilkkinen et al., 2006). Canine diabetes shares some similarities with T1D (O’Kell et al., 2017) and it is hypothesized that antibiotic exposure in pet dogs may also predispose to diabetes. In order to explore this hypothesis, a case control study will be used to review the VetCompassTM database of UK primary-care veterinary practices to identify diabetic cases, and to collect data on historical systemic antibiotic usage.

Project aims:

• To report the incidence of canine diabetes mellitus cases diagnosed in primary care veterinary practices in the United Kingdom (Heeley et al. 2020)
• To describe the pattern of systemic antibiotic usage prior to dogs developing diabetes mellitus
• To explore the prior use of antibiotics on the risk of dogs developing diabetes mellitus

Published paper:

• Assessment of glucocorticoid and antibiotic exposure as risk factors for diabetes mellitus in selected dog breeds attending UK primary-care clinics
  Heeley, A. M., Brodbelt, D. C., O'Neill, D. G., Church, D. B. & Davison, L. J. (2023) VetRecord

References:

Åkerblom, H.K., Knip, M., 1998. Putative environmental factors in Type 1 diabetes. Diabetes. Metab. Rev. 14, 31–68. https://doi.org/10.1002/(SICI)1099-0895(199803)14:1<31::AID-DMR201>3.0.CO;2-A

Brown, K., Godovannyi, A., Ma, C., Zhang, Y., Ahmadi-Vand, Z., Dai, C., Gorzelak, M.A., Chan, Y., Chan, J.M., Lochner, A., Dutz, J.P., Vallance, B.A., Gibson, D.L., 2016. Prolonged antibiotic treatment induces a diabetogenic intestinal microbiome that accelerates diabetes in NOD mice. ISME J. 10, 321–332. https://doi.org/10.1038/ismej.2015.114

Brugman, S., Klatter, F.A., Visser, J.T.J., Wildeboer-Veloo, A.C.M., Harmsen, H.J.M., Rozing, J., Bos, N.A., 2006. Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes? Diabetologia 49, 2105–2108. https://doi.org/10.1007/s00125-006-0334-0

Gülden, E., Wong, F.S., Wen, L., 2015. The gut microbiota and Type 1 Diabetes. Clin. Immunol., Microbiome and Immune Diseases 159, 143–153. https://doi.org/10.1016/j.clim.2015.05.013

Heeley, A.M., O’Neill, D.G., Davison, L.J., Church, D.B., Corless, E.K., Brodbelt, D.C., 2020. Diabetes mellitus in dogs attending UK primary-care practices: frequency, risk factors and survival. Canine Med. Genet. 7, 6. https://doi.org/10.1186/s40575-020-00087-7

Kilkkinen, A., Virtanen, S.M., Klaukka, T., Kenward, M.G., Salkinoja-Salonen, M., Gissler, M., Kaila, M., Reunanen, A., 2006. Use of antimicrobials and risk of type 1 diabetes in a population-based mother–child cohort. Diabetologia 49, 66–70. https://doi.org/10.1007/s00125-005-0078-2

Knip, M., 2012. Descriptive epidemiology of type 1 diabetes—is it still in? Diabetologia 55, 1227–1230. https://doi.org/10.1007/s00125-012-2522-4

O’Kell, A.L., Wasserfall, C., Catchpole, B., Davison, L.J., Hess, R.S., Kushner, J.A., Atkinson, M.A., 2017. Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked? Diabetes 66, 1443–1452. https://doi.org/10.2337/db16-1551

Tapia, G., Størdal, K., Mårild, K., Kahrs, C.R., Skrivarhaug, T., Njølstad, P.R., Joner, G., Stene, L.C., 2018. Antibiotics, acetaminophen and infections during prenatal and early life in relation to type 1 diabetes. Int. J. Epidemiol. 47, 1538–1548. https://doi.org/10.1093/ije/dyy092