Diabetes is an escalating global problem. Specifically in the United States, it is the seventh leading cause of death and affects approximately 30 million people. Significant investment is made in research of the disease each year as treatment options are limited, and a cure has yet to be found. In 2017, the National Institutes of Health awarded approximately $1.105 billion for diabetes research, and many private organizations award millions of dollars every year. An example of such an organization is JDRF (previously known as Juvenile Diabetes Research Foundation), the global leader in funding for type 1 diabetes research. Kaiser Associates named diabetes the third highest indication in their annual report on pharmaceutical research and development spending.
Many scientists receiving this funding perform research in animals to better understand disease development, progression, risk factors, and potential treatments. Often these studies are completed in mouse models as they are easy to genetically modify, providing consistent access to a particular facet of disease. 4 Mice are also cheaper and less regulated than larger animals. However, many differences exist between internal systems and how the disease presents in mice and humans.
A paper published in the June 2017 issue of Diabetes discussed the advantages of canine models as diabetes occurs naturally in several species.4 Recent studies have also shown how similar canine and human gut microbiomes and responses to diet are.5 This combined with comparable disease pathogenesis make canines an attractive model for diabetes research.
Swine are also becoming an increasingly attractive model. Like canines, swine share several attributes with humans including an omnivorous diet, anatomy and physiology of the gastrointestinal tract, and metabolism.6 In addition, the size, shape, and position of the pancreas, especially in minipigs, is very analogous to that of humans.6
Large animals are more highly protected than rodents. Consequently, researchers must defended their use of large animals and show how they will limit pain and stress. Traditional methods of studying diabetes require manual blood draws, intermittently, over a specified time period to determine glucose levels. This method involves a great deal of animal handling and does not provide a full glucose profile.
DSI has developed a new solution which allows researchers to obtain second-by-second glucose data from conscious, freely-moving large animals, such as canines and swine, using telemetry. With this solution, a maximum of three blood samples are required per week for calibration purposes. As a result, animals will experience less pain and stress through a dramatic reduction in animal handling and less frequent drawing of blood.7,8 Greater than 90% of telemetry data sets are free from stress. These conscious, stress-free data are both superior and predictive.9,10 In fact, the American Heart Association officially endorses the use of telemetry for many studies involving blood pressure for nonclinical drug safety assessment.11
Continuous glucose telemetry allows for quantification of glucose homeostasis including assessments of averages, standard deviations, glycemic variability and more. Intermittent sampling requires manual blood draws, making it impossible to get the same quantity of data, and when the samples are spaced far apart (e.g. weekly or once daily), the researcher has no insight into what happens between those measurements. Consequently, glucose homeostasis must be inferred.
Higher quality data typically result in smaller sample sizes as they provide the opportunity to use alternate study designs. Examples of alternate designs include those in which each animal can be used as its own control and more efficient use of an animal such that multiple experiments can be performed within an animal over the course of 4-8 weeks. Therefore, in many applications fewer animals are necessary to complete a research project, aiding in the researcher’s defense of large animal use.9
DSI currently offers glucose telemetry solutions for mice and rats, and the large animal solution is expected to be released mid-2018. To learn more about our continuous glucose telemetry solutions, visit our website or download our free whitepaper.
References
1 American Diabetes Association. (2018). “Overall Numbers, Diabetes and Prediabetes”. Statistics About Diabetes. http://www.diabetes.org/diabetes-basics/statistics/
2 Center for Disease Control and Prevention. (2017). “Diabetes”. National Center for Health Statistics. https://www.cdc.gov/nchs/fastats/diabetes.htm
3Mayo Clinic. (2018). “Diabetes”. Diseases and Conditions. https://www.mayoclinic.org/diseases-conditions/diabetes/diagnosis-treatment/drc-20371451
4O’Kell A.L., Wasserfall C., Catchpole B., Davison L.J., Hess R.S., 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(6): 1443-1452. https://doi.org/10.2337/db16-1551
5Coelho L.P., Kultima J.R., Costea P.I., Fournier C., Pan Y., Czarnecki-Maulden G., Hayward M.R., Forslund S.K., Benedikt Schmidt T.S., Descombes P., Jackson J.R., Li Q., Bork P. (2018). “Similarity of the dog and human gut microbiomes in gene content and response to diet”. Microbiome. https://doi.org/10.1186/s40168-018-0450-3
6Kingfisher Biotech, Inc. (2018). “Swine as an Animal Model”. Kingfisher Biotech Circular. https://www.kingfisherbiotech.com/newsletter/Swine_Animal_Model_Newsletter.pdf
7Ping X, Yao Z, Nawrocki A, Doerning B, Johnson C, Shen X. Telemetry for Continuous Glucose Monitoring in Rats. Poster P296, AALAS 67th National Meeting, Charlotte, NC, October 30-November 3, 2015
8Handling and Restraint, https://www.nc3rs.org.uk/handling-and-restraint. Accessed 13 Feb 2017
9Kramer K, Kinter LB. Evaluation and applications of radiotelemetry in small laboratory animals. Physiological Genomics 2003;13(3):197–205. doi: 10.1152/physiolgenomics.00164.2002
10Morton DB, Hawkins P, Bevan R, Heath K, Kirkwood J, Pearce P, Scott L, Whelan G, Webb A, Refinements in telemetry procedures: Seventh report of BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement, Part A, Laboratory Animals, 2003;37(4):261-299. doi: 10.1258/002367703322389861
11Kurtz TW, Griffin KA, Bidani AK, Davisson RL, Hall JE. AHA Scientific Statement: Recommendations for Blood Pressure Measurement in Humans and Experimental Animals. Part 2: Blood Pressure Measurement in Experimental Animals. Hypertension 2005;45:299-310. doi: 10.1161/01.HYP.0000150857.39919.cb