Diabetes affects an estimated 422 million people worldwide and is the fourth leading cause of death along with other blood and endocrine diseases.1,2 There are two types of diabetes. Type 1 typically stems from genetics and type 2 is largely attributed to lifestyle factors such as obesity and lack of exercise.3 Current treatments for both types of diabetes include administering insulin, monitoring blood sugar levels, maintaining a healthy weight, and consistent exercise. Few drugs are available to manage symptoms and no cure currently exists. Diabetes research is focused on better understanding factors that play a role in the development of disease as well as searching for more effective treatment and preventative options.
Animal Models of Diabetes
Large animal models including canines, swine, and primates are commonly used in diabetes research due to their physiologic similarities to humans. Primates are an ideal model as they have the most metabolic similarities with humans. However, canines and swine also share similarities in gastrointestinal anatomy and metabolic physiology with humans.4
Rodent models are commonly used in diabetes research due to their lower cost and ability to be genetically modified to represent patient populations. Monogenic models are commonly used to model defective leptin signaling leading to hyperphagia and obesity. Polygenic models are believed to be more accurate models of human disease as they allow a variety of genotypes and susceptibilities to be examined. Induced models are also common in diabetes research, typically through diet or chemicals such as streptozotocin (STZ).4
Diabetes Publications Citing Use of HD-XG
Non-insulin determinant pathways maintain glucose homeostasis upon metabolic surgery
Historically, scientists believed insulin was the only hormone that effects glycemia. However, Roux-en-Y gastric bypass surgery (RYGB) has been shown to remedy hyperglycemia and hyperinsulinemia, even though the patient continues to experience insulin resistance. This research team hypothesized that metabolic surgery may open unique pathways for maintenance of glucose homeostasis and studied the effects of RYGB on insulin production. They used DSI’s HD-XG telemetry implant to continuously monitor blood glucose in a STZ-induced mouse model of diabetes. The results supported the team’s hypothesis, showing rearrangement of the gastrointestinal tract opens other pathways for glucose homeostasis maintenance. The study indicated the metabolic profile shifted to fatty acid oxidation rather than glucose utilization, reduced energy uptake of the gut thereby activating multiple metabolic pathways, and enhanced energy expenditure.5
Sustained effect of glucagon on body weight and blood glucose: Assessed by continuous glucose monitoring in diabetic rats
Glucagon is often used to treat insulin-induced hypoglycemia and is believed to play a role in body weight management. This research team looked to understand the pharmacodynamics of glucagon after repeat dosing. Specifically, they assessed the effects of various insulin doses on blood glucose levels alone and in combination with a long acting glucagon analog (LAG). They used DSI’s continuous glucose telemetry to monitor blood glucose in a STZ-induced rat model as it permitted more thorough analysis of glucose regulation than intermittent blood sampling. The results showed a combination of insulin and LAG decreased body weight without affecting food intake and the blood glucose-lowering effect of insulin was prolonged. These results suggest the combination could serve as an effective treatment for diabetes.6
Continuous Blood Glucose Monitoring Reveals Enormous Circadian Variations in Pregnant Diabetic Rats
Gestational diabetes is becoming increasingly common among women of modern western countries. It can cause health issues for the mother and fetus during pregnancy but can also affect the child’s health later in life. A great deal of research has been conducted on gestational diabetes in rats utilizing intermittent blood sampling. This publication cites another recent study in which an increased circadian variability of blood glucose was identified using continuous glucose measurement, showing single daily measurements were inadequate to fully understand glycemic status. Therefore, this research team wanted to use continuous blood glucose measurements in pregnant diabetic rats, for the first time, to better understand the influence pregnancy has on blood glucose in diabetic and normoglycemic status. They utilized DSI’s continuous glucose telemetry to monitor blood glucose throughout pregnancy. The results indicated circadian variation in blood glucose levels which was more pronounced in diabetic pregnant rats. The diabetic rats were also less active than the normoglycemic rats. The team also reported a calculation showing that continuous blood glucose measurement reduces the number of animals needed in a study to make conclusions in an experiment by decreasing variability and standard deviation.7
Continuous measurements of glucose are thought to be more translatable to clinical applications as they more closely mirror human experience and offer more data than is possible with intermittent sampling. Telemetry offers numerous benefits to researchers and the animals used in a study. The most important benefits are improved animal welfare, higher quality data, advanced study designs, and, in many cases, cost savings. DSI’s automated system monitors and collects continuous glucose data from conscious, freely moving mice, rats, pigs, nonhuman primates, dogs, and other large animals.
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1World Health Organization. (2019). “Diabetes”. https://www.who.int/health-topics/diabetes
2Droger S. (2019). “The Leading Cause of Death in the World”. The Street. https://www.thestreet.com/world/leading-causes-of-death-world-14869811
3National Institute of Diabetes and Digestive and Kidney Diseases. (2019). “Risk Factors for Type 2 Diabetes”. https://www.niddk.nih.gov/health-information/diabetes/overview/risk-factors-type-2-diabetes
4Fang JY, Lin CH, Huang TH, Chuang SY. (2019). “In Vivo Rodent Models of Type 2 Diabetes and Their Usefulness for Evaluating Flavonoid Bioactivity”. Nutrients, 11(3): 530. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470730/
5Lu Z, Wei X, Sun F, Zhang H, Gao P, Pu Y, Wang A, Chen J, Tong W, Li Q, Zhou X, Yan Z, Zheng H, Yang G, Huang Y, Liu D, Zhu Z. (2018). “Non-insulin determinant pathways maintain glucose homeostasis upon metabolic surgery”. Cell Discovery, 4(1). https://www.nature.com/articles/s41421-018-0062-x
6Pedersen C, Porsgaard T, Thomsen M, Rosenkilde MM, Roed NK. (2018). “Sustained effect of glucagon on body weight and blood glucose: Assessed by continuous glucose monitoring in diabetic rats”. PLOS ONE. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194468
7Golic M, Kräker K, Fischer C, Alenina N, Haase N, Herse F, Schütte T, Henrich W, Müller DN, Busjahn A, Bader M, Dechend R. (2018). “Continuous Blood Glucose Monitoring Reveals Enormous Circadian Variations in Pregnant Diabetic Rats”. Frontiers in Endocrinology. https://www.frontiersin.org/articles/10.3389/fendo.2018.00271/full