Research with dogs develops an artificial pancreas to treat diabetes
White Coat Waste is a conservative animal rights organization devoted to the elimination of animal research. Its first target is biomedical research conducted using dogs at the US Department of Veterans Affairs (VA). Unfortunately, this campaign is gaining traction. While White Coat Waste is supported mainly by Republicans, some Democrat representatives like Dina Titus (Nevada) and Ted Lieu (California) have expressed their support. In view of that, it is important to highlight the remarkable achievements of dog research at the VA and the tremendous loss that its cancellation would be for Veterans and the general public.
Diabetes is a nasty disease that affects millions of people worldwide and continues to increase. It is a metabolic disorder in which the body becomes incapable of controlling the blood levels of glucose, either because the pancreas fails to produce enough insulin (type 1) or because cells in the body fail to respond to insulin (type 2). Untreated, diabetes can lead to cardiovascular disease, stroke, kidney disease, neuropathic pain, gangrene of the extremities, amputations, blindness, and death. In 2014, 422 million people had diabetes worldwide (8.5% of the population). These numbers have more than tripled since 1980 (108 million; 4.7% of the population) and continue to increase due to poor dietary habits and lack of exercise. The annual number of deaths worldwide was estimated at 4.9 million in 2014. The incidence of diabetes is particularly high in the USA and other developed countries, but it is increasing fast in Asia and Africa. In the USA, diabetes has a high impact in Veterans: one in four patients receiving care at the US Department of Veterans Affairs (VA) has diabetes. This makes it a high priority for medical research at the VA.
People with serious cases of diabetes need multiple daily injections of insulin. Failure to administer the insulin appropriately can lead to kidney failure, amputations, blindness, coma, and even death. However, the dose of insulin has to be tuned to the needs of the body. To do this, patients measure the glucose level in their blood by drawing blood from their fingers using needle sticks. This has to be done several times a day in order to calculate and inject insulin according to the blood glucose levels. An artificial pancreas has been developed at the VA to help improve the outcomes for diabetic patients. This device measures glucose in the blood in real time and automatically administers the right dose of insulin. This technology will dramatically improve the patient’s quality of life and reduce life-threatening complications. It would also tremendously reduce diabetes-related healthcare costs.
This research project was initiated decades ago by Dr. Seymour Levin, a VA endocrinologist who specialized in diabetes and was horrified by the large number of VA patients who needed amputations because of problems with properly administering insulin to treat their diabetes. He obtained funds from the Mann Foundation. In the early 1980s, the Mann Foundation created a company called MiniMed Technologies to design an insulin pump that patients could wear throughout the day. MiniMed Technologies used dogs at the VA diabetes laboratory to test prototypes of this pump. In the early 2000s the company was acquired by Medtronic, which has been fully supporting this research project ever since. No taxpayer money has been used for it, a detail that seems to be important for White Coat Waste.
Taking advantage of new computer technology, the device being developed incorporates not only an insulin pump but also a glucose sensor and software to calculate the amount of insulin to be injected into the blood according to the glucose level. This makes it a true artificial pancreas. Working with dogs allows researchers to do the pre-clinical testing of the artificial pancreas required for approval by the USA Food and Drug Administration (FDA) at the same time that the hardware and the software are refined and improved.
Why use dogs for this research project? Animals like mice, rats or guinea pigs are too small for the devices being tested and their blood volume is not large enough to allow for frequent blood sampling without causing them harm. On the other hand, dogs have been an important model for metabolic studies and can replicate human diabetes quite well (much early research into diabetes and insulin relied on research in dogs). They can also be used for long-term studies lasting years, which are not possible in rodents. The sensors and catheters implanted in the dogs are the same ones to be used in humans, and the dogs adapt very well to wearing them. Dogs also like interacting with humans and can be trained to go along with these painless procedures without needing to be anesthetized or restrained. Other large animals like pigs and sheep were tried and were found to be far less suitable than dogs for this work.
The standard procedure consists of having the dog rest on a soft bed, unrestrained. Glucose sensors are inserted under the skin and an insulin pump is attached via a subcutaneous catheter (similar to a human patient using these devices). The procedures are painless and the dog soon becomes habituated to them. The dog is given a small amount of glucose solution to raise its blood-glucose level in order to see how the experimental sensor, software, and pump respond. Blood samples are then tested on a large and expensive glucose analyzer to see how well the sensor is working.
The dogs in the VA diabetes research project are very well cared for, and the diabetic ones are maintained on insulin pumps. Pet dogs sometimes develop diabetes as they age. Just like humans, they develop cataracts, kidney problems and all the other complications of diabetes. Even when they are given insulin injections under a veterinarian’s care, they all die within 1-2 years. In contrast, the diabetic dogs in this research program are maintained free of symptoms by the insulin pumps and live at least a decade with no cataracts or other diabetes complications. Non-diabetic dogs are adopted out at the end of the study period whenever feasible.
On September 28, 2016, the FDA approved the first artificial pancreas, the Medtronic’s MiniMed 670G System, intended to automatically monitor blood-glucose levels and adjust basal insulin doses in people with type 1 diabetes. The pre-clinical testing of this device was all done on dogs at the VA diabetes research laboratory. However, the research project is ongoing and much work remains to be done. If it is canceled due to political pressure from White Coat Waste, it would be a huge loss for Veterans and the millions of people worldwide who need more reliable ways to treat their diabetes.
Juan Carlos Marvizon, Ph.D.
References: 1. Grosman B, Voskanyan G, Loutseiko M, Roy A, Mehta A, Kurtz N, Parikh N, Kaufman FR, Mastrototaro JJ, Keenan B. Model-based sensor-augmented pump therapy. J Diabetes Sci Technol. 2013 Mar 1;7(2):465-77. 2. Loutseiko M, Voskanyan G, Keenan DB, Steil GM. Closed-loop insulin delivery utilizing pole placement to compensate for delays in subcutaneous insulin delivery. J Diabetes Sci Technol. 2011 Nov 1;5(6):1342-51. 3. Panteleon AE, Loutseiko M, Steil GM, Rebrin K. Evaluation of the effect of gain on the meal response of an automated closed-loop insulin delivery system. Diabetes. 2006 Jul;55(7):1995-2000.